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Potential Use of Silver Nanoparticles as an Additive in Animal Feeding

Authors:

Abstract

Research included in this work has been funded by Laboratorios Argenol, S.L. (Zaragoza, Spain), through the projects OTRI 2006/0279, OTRI 2007/0640 and DEX-600100-2008-23. J. Ducha (University of Zaragoza), M.A. Latorre (Centro de Investigación y Tecnología de Aragón), J. Prieto and E. Gonzalo have been involved in the experimental research included in this paper.
Potential use of silver nanoparticles as an additive in animal feeding 325
Potential use of silver nanoparticles as an additive in animal feeding
Manuel Fondevila
X
Potential use of silver nanoparticles as an
additive in animal feeding
Manuel Fondevila
Instituto Universitario de Experimentación en Ciencias Ambientales,
Departamento de Producción Animal y Ciencia de los Alimentos, Universidad de
Zaragoza, M. Servet 177, 50013 Zaragoza
Spain
1. Abstract
Among other uses, metallic silver and silver salts have currently been applied as
antimicrobial agents in many aspects of medical industries, such as coating of catheters,
dental resin composites and burn wounds, as well as in homeopathic medicine, with a
minimal risk of toxicity in humans. However, their use in animal feeding as prebiotics have
remain minimised, mostly because of the low cost antibiotics used as growth promoters in
the second half of the XX Century. However, after the ban of this practice in the European
Community, silver compounds appear as a potential alternative to other already in use,
such as organic acids, oligosaccharides, plant extracts, etc. The major concerns about the safe
use of an additive in animal feeding are its effective role as antimicrobial, acting selectively
over potential pathogens but not over symbiotic microbial communities; a low toxic effect
over the animal and its human consumer; and a low risk of environmental pollution.
Metallic silver nanoparticles (up to 100 nm) allow for a higher antimicrobial effect than
silver salts, are more resistant to deactivation by gastric acids and have a low absorption rate
through the intestinal mucosa, thus minimising its potential risk of toxicity. Besides, it has
been shown that the doses that promote animal physiological and productive effects are
very low (20 to 40 ppm), especially compared to the 10 to 100-fold higher concentration used
with other metallic compounds such as copper and zinc, thus precluding a harmful
environmental effect. This chapter describes the reasons why silver nanoparticles could be
applied to animal feeding, and provides with some available data in this regard. In any case,
its registration as feed additive is a previous requisite before being applied in practical
conditions.
2. Introduction
From the second half of the XX Century, the modern application of technology on animal
production has been associated to the intensification of the applied systems, looking for a
higher economic profitability by reducing the time and increasing the total magnitude of
production. The necessary shortening of the productive cycles and the earlier weaning of
17
Silver Nanoparticles326
animals leads to an increasing of sensitivity of animals, adapted to focus all their
physiological resources to high growth performances and consequently making them more
sensitive to the environmental conditions and the infection by different diseases, not
necessarily of severe gravity, but that in any case produce considerable reductions in
productivity. In terms of animal feeding and nutrition, this situation allowed to the
transition from the concept of giving nutrients to meet the needs for improving growth as
the basic rule to, once this has been assumed, the use of additives to improve productive
performances over nutritive standards by reaching an optimum health status of animals.
Any substance is considered as a feed additive when, not having a direct utilisation as
nutrient, is included at an optimum concentration in diet or in the drinking water to exert a
positive action over the animal health status or the dietary nutrient utilisation. Because of their
chemical nature as active principles, are generally included in very small proportions in diet.
With the onset of the mentioned productive situation, the use of antibiotics as feed additives –
or growth promoters – became predominant over other alternatives, because of their low cost
and high and uniform response. It has to be considered that the use of antibiotics as growth
promoters, given at sub therapeutical levels to all animals and for prolonged periods of time, is
different to their use as therapeutics, administered at higher proportions to sick animals and
only until recovery. Briefly, if a small amount of a substance selectively acts against some
harmful microbial species occasionally established or transient in the digestive tract, thus
controlling the microbial equilibrium of its microbiota, host animals would need to spend less
metabolic effort in the immunological control of the situation. Then they would use the extra
nutrients for other physiological purposes, thus reaching better productive performances. In
this scenario, the magnitude of such growth promoter substances will be highest in young
weaned animals, which low immune development and high growth requirements make them
more exposed to pathological challenges. It has been reported that using antibiotics as growth
promoters in diets increases weight gain and reduces feed to gain ratio (the amount of feed
ingested to reach each unit of weight gain) in pigs by 0.16 and 0.07, respectively (Cromwell,
1991). It has to be noticed that, whereas this concept of host health improvement through
microbial manipulation is generally applied for monogastric animals (pigs, poultry, rabbits,
etc.), it is not totally so for ruminants, where the search of the digestive health interacts with
the presence in former sites of the tract of a large fermentation chamber of extreme importance
for the ruminant physiology.
As it has been shown that the continuous use of antibiotics as growth promoters provoke
the retention in animal tissues and that the human consumption of such animal products
would potentially increase processes of antibiotic resistance, movements of social pressure
towards food security were claiming for a strict control and against their use in animal
feeding, reaching the banning of using antibiotics as growth promoters from 2006 in the
European Community (CE 1831/2003). In other way, the use of some trace elements such as
zinc and copper, that have been systematically included as growth promoters in diets for
weaned piglets because of their beneficial role in pig health status (Hahn & Baker 1993;
Smith et al., 1997) have been also restricted to those levels that satisfy the metabolic needs of
animals because of both their retention in animal tissues and environmental hazard. The
addition of high doses of zinc (from 2500 to 3500 ppm, as zinc oxide) or copper (from 150 to
250 ppm, as copper sulphate) modulates the microbial status of the digestive tract and
reduce the incidence of post-weaning diarrhoea (Jensen-Waern et al., 1998; Broom et al.,
2006), generally promoting increases in productive performances (Hill et al., 2000; Case &
Carlson, 2002). However, it remains unclear to what extent the response is associated with
its role over the digestive microbial ecosystem (Hogberg et al., 2005) or directly over the
piglet metabolism (Zhou et al., 1994), by affecting the secretion and activity of pancreatic
and intestinal digestive enzymes or the maintenance of the morphology of the intestinal
mucosa (Li et al., 2001; Hedemann et al., 2006).
Considerable efforts have been made to look for alternatives to antibiotics growth promoters
in animal feeding during the last three decades. Among the most widely used products in
pig and poultry production can be cited the organic acids (Partanen & Mroz, 1999;
Ravindran & Kornegay, 1993), plant extracts (Cowan 1999; Burt 2004), oligosaccharides
(Mull & Perry 2004) or probiotics (Gardiner et al., 2004).
3. Silver as antimicrobial
Silver compounds have been historically used to control microbial proliferation (Wadhera &
Fung, 2005). The antifungal and antibacterial effect of silver nanoparticles, even against
antibiotic-resistant bacteria (Wright et al., 1994; 1999) has been demonstrated in in vitro
conditions. Nowadays, silver compounds are routinely applied in a wide array of industrial
and sanitary fields, such as coating of catheters and surgery material, the production of
synthetic compounds for odontology, treatment of burn injuries, homeopathic medicine or
water purification (Spencer, 1999; Klasen, 2000; Wadhera & Fung, 2005; Atiyeh et al., 2007;
Hwang et al., 2007).
Traditionally, silver has been used as salts (ionic form), mainly nitrate, sulphate or chloride.
However, silver cation is converted into the less effective silver chloride in the stomach or
bloodstream, and can form complexes with various ligands. Silver nitrate is unstable, and can
be toxic to tissues (Atiyeh et al., 2007). In contrast, metallic silver in form of colloidal solution
or as 5 to 100 nm nanoparticles is more stable to hydrochloric acid, is absorbed at a much
lower extent by euchariotic cells and therefore is minimally toxic, and at the same time exert a
higher antimicrobial effect (Choi et al., 2008), which explains why its use has been promoted in
the last decades (Atiyeh et al., 2007). Lok et al. (2006) showed that, even though silver
nanoparticles and silver ions in form of silver nitrate have a similar mechanism of action, their
effective concentrations are at nanomolar and micromolar levels, respectively.
Silver exerts its antimicrobial activity through different mechanisms. It has been reported to
uncouple the respiratory electron transport from oxidative phosphorylation and to inhibit
respiratory chain enzymes (Schreurs & Rosemberg, 1982; Bard & Holt, 2005). Silver also
adheres to bacterial surface, thus altering membrane functions, leading to a dissipation of
the proton motive force (Percival et al., 2005; Lok et al., 2006), and interacts with nucleic acid
bases, inhibiting cell replication (Wright et al., 1994; Yang et al., 2009). Some authors have
demonstrated its toxic effect over different serovars of Escherichia coli (Zhao & Stevens, 1998;
Sondi & Salopek-Sondi, 2004; Jung et al., 2008) and Streptococcus faecalis (Zhao & Stevens,
1998), but its observed effect over Staphylococcus aureus has been variable (Li et al., 2006;
Kim et al., 2007; Jung et al., 2008). Yoon et al. (2007) observed a higher effect of silver
nanoparticles on Bacillus subtilis than on Escherichia coli, suggesting a selective antimicrobial
effect, possibly related to the structure of the bacterial membrane, although Singh et al.
(2008) assume higher sensitivity of Gram-negative bacteria to treatment with nanoparticles.
The possible effects of metallic silver and silver ions over microorganisms from the digestive
tract are scarcely documented. The selective response of silver in such ecosystem, with a
Potential use of silver nanoparticles as an additive in animal feeding 327
animals leads to an increasing of sensitivity of animals, adapted to focus all their
physiological resources to high growth performances and consequently making them more
sensitive to the environmental conditions and the infection by different diseases, not
necessarily of severe gravity, but that in any case produce considerable reductions in
productivity. In terms of animal feeding and nutrition, this situation allowed to the
transition from the concept of giving nutrients to meet the needs for improving growth as
the basic rule to, once this has been assumed, the use of additives to improve productive
performances over nutritive standards by reaching an optimum health status of animals.
Any substance is considered as a feed additive when, not having a direct utilisation as
nutrient, is included at an optimum concentration in diet or in the drinking water to exert a
positive action over the animal health status or the dietary nutrient utilisation. Because of their
chemical nature as active principles, are generally included in very small proportions in diet.
With the onset of the mentioned productive situation, the use of antibiotics as feed additives –
or growth promoters – became predominant over other alternatives, because of their low cost
and high and uniform response. It has to be considered that the use of antibiotics as growth
promoters, given at sub therapeutical levels to all animals and for prolonged periods of time, is
different to their use as therapeutics, administered at higher proportions to sick animals and
only until recovery. Briefly, if a small amount of a substance selectively acts against some
harmful microbial species occasionally established or transient in the digestive tract, thus
controlling the microbial equilibrium of its microbiota, host animals would need to spend less
metabolic effort in the immunological control of the situation. Then they would use the extra
nutrients for other physiological purposes, thus reaching better productive performances. In
this scenario, the magnitude of such growth promoter substances will be highest in young
weaned animals, which low immune development and high growth requirements make them
more exposed to pathological challenges. It has been reported that using antibiotics as growth
promoters in diets increases weight gain and reduces feed to gain ratio (the amount of feed
ingested to reach each unit of weight gain) in pigs by 0.16 and 0.07, respectively (Cromwell,
1991). It has to be noticed that, whereas this concept of host health improvement through
microbial manipulation is generally applied for monogastric animals (pigs, poultry, rabbits,
etc.), it is not totally so for ruminants, where the search of the digestive health interacts with
the presence in former sites of the tract of a large fermentation chamber of extreme importance
for the ruminant physiology.
As it has been shown that the continuous use of antibiotics as growth promoters provoke
the retention in animal tissues and that the human consumption of such animal products
would potentially increase processes of antibiotic resistance, movements of social pressure
towards food security were claiming for a strict control and against their use in animal
feeding, reaching the banning of using antibiotics as growth promoters from 2006 in the
European Community (CE 1831/2003). In other way, the use of some trace elements such as
zinc and copper, that have been systematically included as growth promoters in diets for
weaned piglets because of their beneficial role in pig health status (Hahn & Baker 1993;
Smith et al., 1997) have been also restricted to those levels that satisfy the metabolic needs of
animals because of both their retention in animal tissues and environmental hazard. The
addition of high doses of zinc (from 2500 to 3500 ppm, as zinc oxide) or copper (from 150 to
250 ppm, as copper sulphate) modulates the microbial status of the digestive tract and
reduce the incidence of post-weaning diarrhoea (Jensen-Waern et al., 1998; Broom et al.,
2006), generally promoting increases in productive performances (Hill et al., 2000; Case &
Carlson, 2002). However, it remains unclear to what extent the response is associated with
its role over the digestive microbial ecosystem (Hogberg et al., 2005) or directly over the
piglet metabolism (Zhou et al., 1994), by affecting the secretion and activity of pancreatic
and intestinal digestive enzymes or the maintenance of the morphology of the intestinal
mucosa (Li et al., 2001; Hedemann et al., 2006).
Considerable efforts have been made to look for alternatives to antibiotics growth promoters
in animal feeding during the last three decades. Among the most widely used products in
pig and poultry production can be cited the organic acids (Partanen & Mroz, 1999;
Ravindran & Kornegay, 1993), plant extracts (Cowan 1999; Burt 2004), oligosaccharides
(Mull & Perry 2004) or probiotics (Gardiner et al., 2004).
3. Silver as antimicrobial
Silver compounds have been historically used to control microbial proliferation (Wadhera &
Fung, 2005). The antifungal and antibacterial effect of silver nanoparticles, even against
antibiotic-resistant bacteria (Wright et al., 1994; 1999) has been demonstrated in in vitro
conditions. Nowadays, silver compounds are routinely applied in a wide array of industrial
and sanitary fields, such as coating of catheters and surgery material, the production of
synthetic compounds for odontology, treatment of burn injuries, homeopathic medicine or
water purification (Spencer, 1999; Klasen, 2000; Wadhera & Fung, 2005; Atiyeh et al., 2007;
Hwang et al., 2007).
Traditionally, silver has been used as salts (ionic form), mainly nitrate, sulphate or chloride.
However, silver cation is converted into the less effective silver chloride in the stomach or
bloodstream, and can form complexes with various ligands. Silver nitrate is unstable, and can
be toxic to tissues (Atiyeh et al., 2007). In contrast, metallic silver in form of colloidal solution
or as 5 to 100 nm nanoparticles is more stable to hydrochloric acid, is absorbed at a much
lower extent by euchariotic cells and therefore is minimally toxic, and at the same time exert a
higher antimicrobial effect (Choi et al., 2008), which explains why its use has been promoted in
the last decades (Atiyeh et al., 2007). Lok et al. (2006) showed that, even though silver
nanoparticles and silver ions in form of silver nitrate have a similar mechanism of action, their
effective concentrations are at nanomolar and micromolar levels, respectively.
Silver exerts its antimicrobial activity through different mechanisms. It has been reported to
uncouple the respiratory electron transport from oxidative phosphorylation and to inhibit
respiratory chain enzymes (Schreurs & Rosemberg, 1982; Bard & Holt, 2005). Silver also
adheres to bacterial surface, thus altering membrane functions, leading to a dissipation of
the proton motive force (Percival et al., 2005; Lok et al., 2006), and interacts with nucleic acid
bases, inhibiting cell replication (Wright et al., 1994; Yang et al., 2009). Some authors have
demonstrated its toxic effect over different serovars of Escherichia coli (Zhao & Stevens, 1998;
Sondi & Salopek-Sondi, 2004; Jung et al., 2008) and Streptococcus faecalis (Zhao & Stevens,
1998), but its observed effect over Staphylococcus aureus has been variable (Li et al., 2006;
Kim et al., 2007; Jung et al., 2008). Yoon et al. (2007) observed a higher effect of silver
nanoparticles on Bacillus subtilis than on Escherichia coli, suggesting a selective antimicrobial
effect, possibly related to the structure of the bacterial membrane, although Singh et al.
(2008) assume higher sensitivity of Gram-negative bacteria to treatment with nanoparticles.
The possible effects of metallic silver and silver ions over microorganisms from the digestive
tract are scarcely documented. The selective response of silver in such ecosystem, with a
Silver Nanoparticles328
wide diversity of species that can exert either symbiotic (positive) or pathogen (negative)
effects, deserves further attention.
4. Other effects of silver
Despite its potential effect on digestive microbial biodiversity and function, other effects of
metallic silver related with host physiological status, such as the immunological status, the
digestive enzymatic activity and intestinal structure can be expected. This can be assumed
considering the chemical similarity of silver with other metals such as zinc and copper and
the characteristics of their antimicrobial response. The capability of zinc and copper to
minimise the negative effect of weaning on the of height of intestinal villi, thus ensuring its
absorbing potential (Li et al., 2001) and the enhancement of the metabolic pancreatic activity
(Zhou et al., 1994) could also be potentially expected with the use of silver. Besides, studies
related with the role of silver nanoparticles on wound treatment show its role on
metalloproteinases regulation, reducing inflammation and favouring cellular apoptosis and
cicatrisation (Wright et al., 2002; Warriner & Burrell, 2005). Lansdown (2002) indicates that
the topic use of silver promotes an increase of zinc and copper concentration over epithelial
tissue, thus indirectly stimulating its positive effects.
A cytotoxic effect of silver on the host animal must also be considered. This has been
occasionally observed in human medicine when chronic (extended in time) treatments with
high doses of silver have been used, often related with the use of silver compounds for
wound healing or in dental implants (Abe et al., 2003; Lam et al., 2004). Chronic ingestion of
silver compounds may lead to its retention in skin, eyes and other organs such as liver, but
it has been generally considered as a cosmetic problem, with minor or nil pathological
symptoms (Lansdown, 2006). Wadhera & Fung (2005) state that no physiological alterations
or damage of organs of patients with argyria (subcutaneous accumulation of silver
associated with silver salts treatment), even with daily intake of 650 mg ionic silver for 10
months (corresponding to a total of 200 g silver intake). The minimal dose causing
generalised argyria in humans has been fixed in 4 to 5 g (Brandt et al., 2005). According to
Ricketts et al. (1970), the minimal dose of silver nitrate to cause inhibition of cell respiration
in tissues is about 25-fold higher to that inhibits growth of Pseudomonas aeruginosa, and
Gopinath et al. (2008) concluded that a necrotic effect on human cells of silver nanoparticles
occur at concentrations above 44 µg/ml (44 ppm). However, no limiting concentration of
silver intake has been fixed for humans, although the US Environmental Protecting Agency
(EPA) recommends a maximum silver dose in drinking water for chronic or short term (1 to
10 days) intake of 0.05 and 1.14 ppm, respectively (ATSDS 1990).
5. Potential use of silver in animal feeding
In the 50´s, colloidal silver was used as zootechnical additive in poultry diets, but its high
cost at that time avoided its possibility to compete with the lower cost of antibiotics.
Nowadays, the development of industrial processes of silver nanoparticles allows for its
consideration as a potential feed additive, once the banning of the use of antibiotics as
growth promoters. However, the availability of results testing metallic silver nanoparticles
in animal production experiments is very scarce. It has been observed in vitro that the
proportion of coliforms in pigs ileal contents was linearly reduced (P<0.05), whereas no
effect was observed on lactobacilli proportion, when the concentration of colloidal silver in
the medium increased from 0 to 25, 50 or 100 ppm (Fondevila et al., 2009). According to
these results, metallic silver nanoparticles would reduce the viability of organisms with a
potentially harmful effect, such as coliforms, whereas it does not affect lactobacilli, which
positively compete against pathogens proliferation and reduce their virulence (Blomberg et
al., 1993). A trend (P = 0.07) to a coliform reduction in ileal contents was also observed in
vivo by Fondevila et al. (2009) when 20 and 40 ppm of metallic silver nanoparticles were
given to weaned piglets as metallic silver adsorbed in a sepiolite matrix (ARGENTA,
Laboratorios Argenol S.L., Spain) as antimicrobial and growth promoter for weaned pigs
during their transition phase (from 5 to 20 kg weight). Besides, although concentration of
major bacterial groups in the ileum of pigs were not markedly affected, the concentration of
the pathogen Clostridium perfringens/ Cl. histolyticum group was reduced with 20 ppm silver
(P = 0.012). In the same way, Sawosz et al. (2007) did not observed a major effect of colloidal
silver on bacterial concentration in the digestive tract of quails, but only a significant
increase in lactic acid bacteria was observed with 25 ppm.
Results on productive performances in several experiments with pigs and poultry carried
out by our group were variable (Table 1): a numerical increase in daily growth was
generally observed when 20 ppm silver were added compared with the control (no silver),
but this effect was not generally significant. As the productive responses to an additive that
improves the sanitary status of animals are in general inversely proportional to the
environmental quality of the productive site (Cromwell 1995), it is likely that under the
stress conditions of commercial farms the concentration of pathogenic bacteria increased
and thus the effect of silver would be more manifested. In the same way, a lack of effect of
adding zinc oxide had also been sometimes reported (Jensen-Waern et al., 1998; Broom et al.,
2006), which would partly explain this lack of significant results. Studies in animals as
models for humans have shown that high silver concentrations (between 95 and 300 ppm,
corresponding to 2.4 and 7.5-fold the concentrations used in these experiments) in form of
silver salts and given as chronic dose (for more than 18 weeks) reduce weight of mice
(Rungby & Danscher 1984) and turkeys (Jensen et al., 1974). However, these dosing
conditions are considered of much higher toxic potential than low concentration metallic
silver given for short periods of time (Wadhera & Fung 2005). In an experiment (E. Gonzalo,
M.A. Latorre & M. Fondevila, unpublished) where pigs were given 0, 20 and 40 ppm silver
from weaning to slaughter weight (91 kg), the feed to gain ratio (amount of feed per unit of
increased weight) was reduced (P= 0.03) by silver addition, indicating a higher growth
efficiency and showing a reduction in overall production cost.
Another important aspect to verify when an additive is promoted to use is to what extent it
does not challenge the health of the potential consumer. Inclusion of 2500 to 3000 ppm zinc
in diets for post-weaning pig leads to tissue retention from 220 µg/g (Jensen-Waern et al.,
1998; Carlson et al., 1999) to 445 µg/g (Zhang & Guo, 2007) in liver, and retentions up to
3020 µg/g have been reported (Case and Carlson, 2002). In a study carried out with metallic
silver, no silver retention was detected in renal or muscular (semimembranous) tissue in
weaned piglets given 20 or 40 ppm silver for 35 days (n=18), and only 0.435 and 0.837 µg per
g were recorded in liver (Fondevila et al., 2009). Another experiment repeated in the same
conditions (Gonzalo, Latorre & Fondevila, unpublished) showed minimal silver retention in
muscles (0.036 and 0.033 µg/g with 20 and 40 ppm silver in diet) and kidney (0.034 and
0.039 µg/g, respectively) that was observed in 6 out of 8 animals, whereas silver was
Potential use of silver nanoparticles as an additive in animal feeding 329
wide diversity of species that can exert either symbiotic (positive) or pathogen (negative)
effects, deserves further attention.
4. Other effects of silver
Despite its potential effect on digestive microbial biodiversity and function, other effects of
metallic silver related with host physiological status, such as the immunological status, the
digestive enzymatic activity and intestinal structure can be expected. This can be assumed
considering the chemical similarity of silver with other metals such as zinc and copper and
the characteristics of their antimicrobial response. The capability of zinc and copper to
minimise the negative effect of weaning on the of height of intestinal villi, thus ensuring its
absorbing potential (Li et al., 2001) and the enhancement of the metabolic pancreatic activity
(Zhou et al., 1994) could also be potentially expected with the use of silver. Besides, studies
related with the role of silver nanoparticles on wound treatment show its role on
metalloproteinases regulation, reducing inflammation and favouring cellular apoptosis and
cicatrisation (Wright et al., 2002; Warriner & Burrell, 2005). Lansdown (2002) indicates that
the topic use of silver promotes an increase of zinc and copper concentration over epithelial
tissue, thus indirectly stimulating its positive effects.
A cytotoxic effect of silver on the host animal must also be considered. This has been
occasionally observed in human medicine when chronic (extended in time) treatments with
high doses of silver have been used, often related with the use of silver compounds for
wound healing or in dental implants (Abe et al., 2003; Lam et al., 2004). Chronic ingestion of
silver compounds may lead to its retention in skin, eyes and other organs such as liver, but
it has been generally considered as a cosmetic problem, with minor or nil pathological
symptoms (Lansdown, 2006). Wadhera & Fung (2005) state that no physiological alterations
or damage of organs of patients with argyria (subcutaneous accumulation of silver
associated with silver salts treatment), even with daily intake of 650 mg ionic silver for 10
months (corresponding to a total of 200 g silver intake). The minimal dose causing
generalised argyria in humans has been fixed in 4 to 5 g (Brandt et al., 2005). According to
Ricketts et al. (1970), the minimal dose of silver nitrate to cause inhibition of cell respiration
in tissues is about 25-fold higher to that inhibits growth of Pseudomonas aeruginosa, and
Gopinath et al. (2008) concluded that a necrotic effect on human cells of silver nanoparticles
occur at concentrations above 44 µg/ml (44 ppm). However, no limiting concentration of
silver intake has been fixed for humans, although the US Environmental Protecting Agency
(EPA) recommends a maximum silver dose in drinking water for chronic or short term (1 to
10 days) intake of 0.05 and 1.14 ppm, respectively (ATSDS 1990).
5. Potential use of silver in animal feeding
In the 50´s, colloidal silver was used as zootechnical additive in poultry diets, but its high
cost at that time avoided its possibility to compete with the lower cost of antibiotics.
Nowadays, the development of industrial processes of silver nanoparticles allows for its
consideration as a potential feed additive, once the banning of the use of antibiotics as
growth promoters. However, the availability of results testing metallic silver nanoparticles
in animal production experiments is very scarce. It has been observed in vitro that the
proportion of coliforms in pigs ileal contents was linearly reduced (P<0.05), whereas no
effect was observed on lactobacilli proportion, when the concentration of colloidal silver in
the medium increased from 0 to 25, 50 or 100 ppm (Fondevila et al., 2009). According to
these results, metallic silver nanoparticles would reduce the viability of organisms with a
potentially harmful effect, such as coliforms, whereas it does not affect lactobacilli, which
positively compete against pathogens proliferation and reduce their virulence (Blomberg et
al., 1993). A trend (P = 0.07) to a coliform reduction in ileal contents was also observed in
vivo by Fondevila et al. (2009) when 20 and 40 ppm of metallic silver nanoparticles were
given to weaned piglets as metallic silver adsorbed in a sepiolite matrix (ARGENTA,
Laboratorios Argenol S.L., Spain) as antimicrobial and growth promoter for weaned pigs
during their transition phase (from 5 to 20 kg weight). Besides, although concentration of
major bacterial groups in the ileum of pigs were not markedly affected, the concentration of
the pathogen Clostridium perfringens/ Cl. histolyticum group was reduced with 20 ppm silver
(P = 0.012). In the same way, Sawosz et al. (2007) did not observed a major effect of colloidal
silver on bacterial concentration in the digestive tract of quails, but only a significant
increase in lactic acid bacteria was observed with 25 ppm.
Results on productive performances in several experiments with pigs and poultry carried
out by our group were variable (Table 1): a numerical increase in daily growth was
generally observed when 20 ppm silver were added compared with the control (no silver),
but this effect was not generally significant. As the productive responses to an additive that
improves the sanitary status of animals are in general inversely proportional to the
environmental quality of the productive site (Cromwell 1995), it is likely that under the
stress conditions of commercial farms the concentration of pathogenic bacteria increased
and thus the effect of silver would be more manifested. In the same way, a lack of effect of
adding zinc oxide had also been sometimes reported (Jensen-Waern et al., 1998; Broom et al.,
2006), which would partly explain this lack of significant results. Studies in animals as
models for humans have shown that high silver concentrations (between 95 and 300 ppm,
corresponding to 2.4 and 7.5-fold the concentrations used in these experiments) in form of
silver salts and given as chronic dose (for more than 18 weeks) reduce weight of mice
(Rungby & Danscher 1984) and turkeys (Jensen et al., 1974). However, these dosing
conditions are considered of much higher toxic potential than low concentration metallic
silver given for short periods of time (Wadhera & Fung 2005). In an experiment (E. Gonzalo,
M.A. Latorre & M. Fondevila, unpublished) where pigs were given 0, 20 and 40 ppm silver
from weaning to slaughter weight (91 kg), the feed to gain ratio (amount of feed per unit of
increased weight) was reduced (P= 0.03) by silver addition, indicating a higher growth
efficiency and showing a reduction in overall production cost.
Another important aspect to verify when an additive is promoted to use is to what extent it
does not challenge the health of the potential consumer. Inclusion of 2500 to 3000 ppm zinc
in diets for post-weaning pig leads to tissue retention from 220 µg/g (Jensen-Waern et al.,
1998; Carlson et al., 1999) to 445 µg/g (Zhang & Guo, 2007) in liver, and retentions up to
3020 µg/g have been reported (Case and Carlson, 2002). In a study carried out with metallic
silver, no silver retention was detected in renal or muscular (semimembranous) tissue in
weaned piglets given 20 or 40 ppm silver for 35 days (n=18), and only 0.435 and 0.837 µg per
g were recorded in liver (Fondevila et al., 2009). Another experiment repeated in the same
conditions (Gonzalo, Latorre & Fondevila, unpublished) showed minimal silver retention in
muscles (0.036 and 0.033 µg/g with 20 and 40 ppm silver in diet) and kidney (0.034 and
0.039 µg/g, respectively) that was observed in 6 out of 8 animals, whereas silver was
Silver Nanoparticles330
detected in liver of all animals at 0.400 and 0.557 µg/g for 20 and 40 ppm, respectively. It has
to be considered that these concentrations are more than 3000-fold lower than in the case of
zinc and the range is below the EPA recommendation, as it has been commented above.
Further, pigs are not given silver additive during their growth and finishing phases (from 20
to 90-100 kg, commercial slaughter weight), and our group did not detect any traces of silver
in muscles, kidneys or liver of 90 kg pigs receiving the additive up to 20 kg weight, thus
showing the detoxifying capacity of liver to excrete silver (Lansdown, 2006).
In an experiment with broiler chicks as another animal productive species, dosage of
metallic silver nanoparticles (ARGENTA) for 5 weeks was continued by 7 days of non-
supplemented period (Prieto & Fondevila, unpublished). Silver retention was 0.035, 0.031
and 0.045 µg/g in muscular tissue and 0.113, 0.086 and 0.185 µg/g for the same treatments
in liver tissue for 20, 30 and 40 silver ppm in diet, respectively (n=10). Only 5 out of 10
animals given 20 and 30 ppm silver showed detectable concentration in muscles, while 6
and 7 out of 10 animals with the same treatments showed silver concentration in the liver.
Experimental conditions Ag dose
(mg/kg)
Intake
(g/d)
Growth
(g/d)
F:G
(kg/kg) Reference
weaned pigs, n=5, 28 to
35 d age
0
20
40
s.e.m.
162
143
177
--
107
122
157
41.3
Fondevila et al.
(2009)
weaned pigs, n=5, 35 to
42 d
0
20
40
s.e.m.
253
313
365
--
314b
393ab
461 a
36.4
Fondevila et al.
(2009)
weaned pigs, n=6 pens
of 4 pigs, 21 to 35 d
0
20
40
s.e.m.
154b
189a
148 b
8.5
66
102
93
11.0
2.13
1.95
1.70
0.196
Fondevila et al.
(2009)
weaned pigs, n=6 pens
of 4 pigs, 35 to 56 d
0
20
40
s.e.m.
527b
670a
630a
32.3
337
375
347
21.2
1.56b
1.80a
1.82a
0.050
Fondevila et al.
(2009)
weaned pigs, n=6 pens
of 2 pigs, 21 to 147 d;
silver was dosed from
21 to 56 d of age
0
20
40
s.e.m.
1737
1638
1734
46.9
684
677
693
16.8
2.53a
2.42b
2.50ab
0.029
Gonzalo, Latorre
& Fondevila
(unpublished)
broilers, n=8 pens of 28
chicks, 1 to 42 d; silver
was dosed from 1 to 35
d of age
0
20
30
40
s.e.m.
99.7
97.3
96.6
99.0
0.74
54.6
55.3
53.9
54.1
1.28
1.83
1.76
1.79
1.83
0.030
Prieto &
Fondevila
(unpublished)
Table 1. Effect of inclusion of metallic silver nanoparticles (ARGENTA) on productive
performances of animals
F:G, feed to gain ratio, a,b, letters show differences among means (P<0.05)
6. Acknowledgements
Research included in this work has been funded by Laboratorios Argenol, S.L. (Zaragoza,
Spain), through the projects OTRI 2006/0279, OTRI 2007/0640 and DEX-600100-2008-23. J.
Ducha (University of Zaragoza), M.A. Latorre (Centro de Investigación y Tecnología de
Aragón), J. Prieto and E. Gonzalo have been involved in the experimental research included
in this paper.
7. References
Abe, Y.; Ueshige, M.; Takeuchi, M.; Ishii, M. & Akagawa, Y. (2003). Cytotoxicity of
antimicrobial tissue conditioners containing silver-zeolite. International Journal of
Prosthodontology, 16, 141-144.
Agency for Toxic Substances and Diseases Registry (1990). Toxicological profile for silver.
U.S. Public Health Service, 145 pp.
Atiyeh, B.S.; Costagliola, M.; Hayek, S.N. & Dibo, S.A. (2007). Effect of silver on burn wound
infection control and healing: review of the literature. Burns, 33, 139-148.
Bard, A.J. & Holt, K.B. (2005). Interaction of silver ions (I) with the respiratory chain of
Escherichia coli: an electrochemical and scanning electrochemical study of the
antimicrobial mechanism of micromolar Ag+. Biochemistry, 44, 13214-13223.
Blomberg, L.; Henrikson, A. & Conway, P. L. ( 1993). Inhibition of adhesion of Escherichia coli
K88 to piglet ileal mucus by Lactobacillus spp. Applied and Environmental
Microbiology, 59, 34–39.
Brandt, D.; Park, B.; Hoang, M. & Jacobe, H.T. (2005). Argyria secondary to ingestion of
homemade silver solution. Journal of American Academy of Dermatology, 53, S105-
S107.
Broom, L.J.; Miller, H.M.; Kerr, K.G. & Knapp, J.S. (2006). Effects of zinc oxide and
Enterococcus faecium SF68 dietary supplementation on the performance, intestinal
microbiota and immune status of weaned piglets. Research in Veterinary Science, 80,
45-54.
Burt, S. (2004). Essential oils: their antibacterial properties and potential applications in
foods: a review. International Journal of Food Microbiology, 942, 223-253.
Carlson, M.S.; Hill, G.M. & Link, J.E. (1999). Early- and traditionally weaned nursery pigs
benefit from phase-feeding pharmacological concentrations of zinc oxide: effect on
methallothionein and mineral concentrations. Journal of Animal Science, 77, 1199-
1207.
Case, C.L. & Carlson, M.S. (2002). Effect of feeding organic and inorganic sources of
additional zinc on growth performance and zinc balance in nursery pigs. Journal of
Animal Science, 80, 1917-1924.
Choi, O.; Deng, K.K.; Kim, N.J., Ross, L.Jr.; Surampalli, R.Y. & Hu, Z. (2008). The inhibitory
effects of silver nanoparticles, silver ions and silver chloride colloids on microbial
growth. Water Research, 42, 3066-3074.
Cowan, M.M. (1999). Plant products as antimicrobial agents. Clinical Microbiology Reviews 12,
564-582.
Cromwell, G.L. (1991). Antimicriobial agents. In: Swine nutrition, E.R. Miller, D.E. Ullrey, A.J.
Lewis (Eds.), pp. 297-315, CRC Press, Boca Raton.
Potential use of silver nanoparticles as an additive in animal feeding 331
detected in liver of all animals at 0.400 and 0.557 µg/g for 20 and 40 ppm, respectively. It has
to be considered that these concentrations are more than 3000-fold lower than in the case of
zinc and the range is below the EPA recommendation, as it has been commented above.
Further, pigs are not given silver additive during their growth and finishing phases (from 20
to 90-100 kg, commercial slaughter weight), and our group did not detect any traces of silver
in muscles, kidneys or liver of 90 kg pigs receiving the additive up to 20 kg weight, thus
showing the detoxifying capacity of liver to excrete silver (Lansdown, 2006).
In an experiment with broiler chicks as another animal productive species, dosage of
metallic silver nanoparticles (ARGENTA) for 5 weeks was continued by 7 days of non-
supplemented period (Prieto & Fondevila, unpublished). Silver retention was 0.035, 0.031
and 0.045 µg/g in muscular tissue and 0.113, 0.086 and 0.185 µg/g for the same treatments
in liver tissue for 20, 30 and 40 silver ppm in diet, respectively (n=10). Only 5 out of 10
animals given 20 and 30 ppm silver showed detectable concentration in muscles, while 6
and 7 out of 10 animals with the same treatments showed silver concentration in the liver.
Experimental conditions Ag dose
(mg/kg)
Intake
(g/d)
Growth
(g/d)
F:G
(kg/kg) Reference
weaned pigs, n=5, 28 to
35 d age
0
20
40
s.e.m.
162
143
177
--
107
122
157
41.3
Fondevila et al.
(2009)
weaned pigs, n=5, 35 to
42 d
0
20
40
s.e.m.
253
313
365
--
314b
393ab
461 a
36.4
Fondevila et al.
(2009)
weaned pigs, n=6 pens
of 4 pigs, 21 to 35 d
0
20
40
s.e.m.
154b
189a
148 b
8.5
66
102
93
11.0
2.13
1.95
1.70
0.196
Fondevila et al.
(2009)
weaned pigs, n=6 pens
of 4 pigs, 35 to 56 d
0
20
40
s.e.m.
527b
670a
630a
32.3
337
375
347
21.2
1.56b
1.80a
1.82a
0.050
Fondevila et al.
(2009)
weaned pigs, n=6 pens
of 2 pigs, 21 to 147 d;
silver was dosed from
21 to 56 d of age
0
20
40
s.e.m.
1737
1638
1734
46.9
684
677
693
16.8
2.53a
2.42b
2.50ab
0.029
Gonzalo, Latorre
& Fondevila
(unpublished)
broilers, n=8 pens of 28
chicks, 1 to 42 d; silver
was dosed from 1 to 35
d of age
0
20
30
40
s.e.m.
99.7
97.3
96.6
99.0
0.74
54.6
55.3
53.9
54.1
1.28
1.83
1.76
1.79
1.83
0.030
Prieto &
Fondevila
(unpublished)
Table 1. Effect of inclusion of metallic silver nanoparticles (ARGENTA) on productive
performances of animals
F:G, feed to gain ratio, a,b, letters show differences among means (P<0.05)
6. Acknowledgements
Research included in this work has been funded by Laboratorios Argenol, S.L. (Zaragoza,
Spain), through the projects OTRI 2006/0279, OTRI 2007/0640 and DEX-600100-2008-23. J.
Ducha (University of Zaragoza), M.A. Latorre (Centro de Investigación y Tecnología de
Aragón), J. Prieto and E. Gonzalo have been involved in the experimental research included
in this paper.
7. References
Abe, Y.; Ueshige, M.; Takeuchi, M.; Ishii, M. & Akagawa, Y. (2003). Cytotoxicity of
antimicrobial tissue conditioners containing silver-zeolite. International Journal of
Prosthodontology, 16, 141-144.
Agency for Toxic Substances and Diseases Registry (1990). Toxicological profile for silver.
U.S. Public Health Service, 145 pp.
Atiyeh, B.S.; Costagliola, M.; Hayek, S.N. & Dibo, S.A. (2007). Effect of silver on burn wound
infection control and healing: review of the literature. Burns, 33, 139-148.
Bard, A.J. & Holt, K.B. (2005). Interaction of silver ions (I) with the respiratory chain of
Escherichia coli: an electrochemical and scanning electrochemical study of the
antimicrobial mechanism of micromolar Ag+. Biochemistry, 44, 13214-13223.
Blomberg, L.; Henrikson, A. & Conway, P. L. ( 1993). Inhibition of adhesion of Escherichia coli
K88 to piglet ileal mucus by Lactobacillus spp. Applied and Environmental
Microbiology, 59, 34–39.
Brandt, D.; Park, B.; Hoang, M. & Jacobe, H.T. (2005). Argyria secondary to ingestion of
homemade silver solution. Journal of American Academy of Dermatology, 53, S105-
S107.
Broom, L.J.; Miller, H.M.; Kerr, K.G. & Knapp, J.S. (2006). Effects of zinc oxide and
Enterococcus faecium SF68 dietary supplementation on the performance, intestinal
microbiota and immune status of weaned piglets. Research in Veterinary Science, 80,
45-54.
Burt, S. (2004). Essential oils: their antibacterial properties and potential applications in
foods: a review. International Journal of Food Microbiology, 942, 223-253.
Carlson, M.S.; Hill, G.M. & Link, J.E. (1999). Early- and traditionally weaned nursery pigs
benefit from phase-feeding pharmacological concentrations of zinc oxide: effect on
methallothionein and mineral concentrations. Journal of Animal Science, 77, 1199-
1207.
Case, C.L. & Carlson, M.S. (2002). Effect of feeding organic and inorganic sources of
additional zinc on growth performance and zinc balance in nursery pigs. Journal of
Animal Science, 80, 1917-1924.
Choi, O.; Deng, K.K.; Kim, N.J., Ross, L.Jr.; Surampalli, R.Y. & Hu, Z. (2008). The inhibitory
effects of silver nanoparticles, silver ions and silver chloride colloids on microbial
growth. Water Research, 42, 3066-3074.
Cowan, M.M. (1999). Plant products as antimicrobial agents. Clinical Microbiology Reviews 12,
564-582.
Cromwell, G.L. (1991). Antimicriobial agents. In: Swine nutrition, E.R. Miller, D.E. Ullrey, A.J.
Lewis (Eds.), pp. 297-315, CRC Press, Boca Raton.
Silver Nanoparticles332
Fondevila, M.; Herrer, R.; Casallas, M.C.; Abecia, L. & Ducha, J.J. (2009). Silver nanoparticles
as a potential antimicrobial additive for weaned pigs. Animal Feed Science and
Technology, 150, 259-269.
Gardiner, G.E.; Casey, P.G.; Casey, G.; Lynch, P.B.; Lawlor, P.G.; Hill, C.; Fitzgerald, G.F.;
Stanton, C. & Ross, R.P. (2004). Relative ability of orally administered Lactobacillus
murinus to predominate and persist in the porcine gastrointestinal tract. Applied and
Environmental Microbiology, 70, 1895–1906.
Gopinath, P.; Gogoi, S.K.; Chattopadhyay, A. & Gosh, S.S. (2008). Implications of silver
nanoparticle induced cell apoptosis for in vitro gene therapy. Journal of
Nanobiotechnology, 19, 075104.
Hahn, J.D. & Baker, D.H. (1993). Growth and plasma zinc responses of young pigs fed
pharmacologic levels of zinc. Journal of Animal Science, 71, 3020-3024.
Hedemann, M.S.; Jensen, B.B. & Poulsen, H.D. (2006). Influence of dietary zinc and copper
on digestive enzyme activity and intestinal morphology in weaned pigs. Journal of
Animal Science, 84, 3310-3320.
Hill, G.M.; Cromwell, G.L.; Crenshaw, T.D.; Dove, C.R.; Ewan, R.C.; Knabe, D.A.; Lewis,
A.J.; Libal, G.W.; Mahan, D.C.; Shurson, G.C.; Southern, L.L. & Veum, T.L. (2000).
Growth promotion effects and plasma changes from feeding high dietary
concentrations of zinc and copper to weanling pigs (regional study). Journal of
Animal Science, 78, 1010-1016.
Hogberg, O.; Canibe, N.; Poulsen, H.D.; Hedemann, M.S. & Jensen, B.B. (2005). Influence of
dietary zinc oxide and copper sulphate on the gastrointestinal ecosystem in newly
weaned piglets. Applied and Environmental Microbiology, 71, 2267-2277.
Hwang, M.G. ; Katayama, H. & Ohgaki, S. (2007). Inactivation of Legionella pneumophila and
Pseudomonas aeruginosa: evaluation of the bactericidal ability of silver cations. Water
Research, 41, 4097-4104.
Jensen, LS; Peterson, RP & Falen, L. (1974). Inducement of enlarged hearts and muscular
dystrophy in turkey poults with dietary silver. Poultry Science, 53, 57-64.
Jensen-Waern, M.; Melin, L.; Lindberg, R.; Johanisson, A.; Peterson, L. & Wallgren, P. (1998).
Dietary zinc oxide in weaned pigs-effects on performance, tissue concentrations,
morphology, meutrophil functions and faecal microflora. Research in Veterinary
Science, 64, 225-231.
Jung, W.K.; Koo, H.K.; Kim, K.W.; Shin, S.; Kim, S.H. & Park, Y.H. (2008). Antibacterial
activity and mechanism of action of the silver ion in Staphylococcus aureus and
Escherichia coli. Applied and Environmental Microbiology, 74, 2171-2178.
Kim, J.S.; Kuk, E.; Yu, K.N.; Kim, J.H.; Park, S.J.; Lee, H.J.; Kim, S.H.; Park, Y.K.; Park, Y.H.;
Hwang, C.Y.; Kim, Y.K.; Lee, Y.S.; Jeong, D.H. & Cho, M.H. (2007). Antimicrobial
effect of silver nanoparticles. Nanomedicine: Nanotecnology, Biology and Medicine, 3,
95-101.
Klasen, H.J. (2000). Historical review of the use of silver in the treatment of burns. I. Early
uses. Burns, 26, 117-130
Lam, P.K.; Chan, E.S.; Ho, W.S. & Liew, C.T. (2004). In vitro cytotoxicity testing of
nanocrystalline silver dressing (Acticoat) on cultured keratinocytes. British Journal
of Biomedical Science, 61, 125-127.
Lansdown, A.B. (2006). Silver in health care: antimicrobial effects and safety in use. Current
Problems in Dermatology, 33, 17-34.
Li, B. T.; Van Kessel, A. G.; Caine, W. R.; Huang, S. X. & Kirkwood, R. N. (2001). Small
intestinal morphology and bacterial populations in ileal digesta and feces of newly
weaned pigs receiving a high dietary level of zinc oxide. Canadian Journal of Animal
Science, 81, 511-516.
Li, Y.; Leung, P.; Yao, L.; Song, K.W. & Newton, E. (2006). Antimicrobial effect of surgical
masks coated with nanoparticles. Journal of Hospital Infection, 62, 58-63
Lok, C.N.; Ho, C.M.; Chen, R.; He, Q.Y.; Yu, W.Y.; Sun, H.; Tam, P.K.H.; Chiu, J.F. & Che,
C.M. (2006). Proteomic analysis of the mode of antibacterial action of silver
nanoparticles. Journal of Proteome Research, 5, 916-924.
Mull, A.J. & Perry, F.G. (2001). The role of fructo-oligosaccharides in animal nutrition. In
Recent developments in pig nutrition 3, J. Wiseman y P.C. Garnsworthy (eds.), pp. 79-
105, Nottingham University Press, Nottingham.
Partanen, K.H. & Mroz, Z. (1999) Organic acids for performance enhancement in pig diets.
Nutrition Research Reviews, 12, 117-145.
Percival, S.L.; Bowler, P.G. & Russell, D. (2005). Bacterial resistance to silver in wound care.
Journal of Hospital Infection, 60, 1-7.
Ravindran, V., Kornegay, E.T.,1993. Acidification of weaner pig diets: a review. Journal of
the Science of Food and Agriculture 62, 313-322.
Ricketts, C.R.; Lowbury, E.J.L.; Lawrence, J.C.; Hall, M. & Wilkins, M.D. (1970). Mechanism
of prophylaxis by silver compounds against infection of burns. British Medical
Journal, 2, 444-446.
Rungby, J. & Danscher, G. (1984). Hypoactivity in silver exposed mice. Acta Pharmacologica
Toxicologica, 55, 398-401.
Sawosz, E.; Binek, M.; Grodzik, M.; Zielinska, M.; Sysa, P.; Szmidt, M.; Niemec, T. &
Chwalibog, A. (2007). Influence of hydrocolloidal silver nanoparticles on
gastrointestinal microflora and morphology of enterocytes of quails. Archives of
Animal Nutrition, 61, 444-451.
Schreurs, W.J. & Rosenberg, H. (1982). Effect of silver ions on transport and retention of
phosphate by Escherichia coli. Journal of Bacteriology, 152, 7-13.
Singh, M.; Singh, S., Prasad, S. & Gambhir, I.S. (2008). Nanotechnology in medicine and
antibacterial effect of silver nanoparticles. Digest Journal in Nanomaterials and
Biostructures, 3, 115-122.
Smith, J.W.; Tokach, M.D.; Goodband, R.D.; Nelssen, J.L. & Richert, B.T. (1997). Effects of the
interrelationship between zinc oxide and copper sulfate on growth performance of
early-weaned pigs. Journal of Animal Science, 75, 1861-1866.
Sondi, I. & Salopek-Sondi, B. (2004). Silver nanoparticles as antimicrobial agent : a case study
on E. coli as a model for Gram-negative bacteria. Journal of Colloid Interface Science,
275, 177-182.
Spencer, R.C. (1999). Novel methods for the prevention of infection of intravascular devices.
Journal of Hospital Infection, 43, S127-S135.
Wadhera, A. & Fung, M. (2005). Systemic argyria associated with ingestion of colloidal
silver. Dermatology Online Journal 11, 12 (http://dermatology.cdlib.org/111).
Warriner, R. & Burrell, R.E. (2005). Infection and the chronic wound: a focus on silver.
Advances on Skin Wound Care, 18, 2-12.
Potential use of silver nanoparticles as an additive in animal feeding 333
Fondevila, M.; Herrer, R.; Casallas, M.C.; Abecia, L. & Ducha, J.J. (2009). Silver nanoparticles
as a potential antimicrobial additive for weaned pigs. Animal Feed Science and
Technology, 150, 259-269.
Gardiner, G.E.; Casey, P.G.; Casey, G.; Lynch, P.B.; Lawlor, P.G.; Hill, C.; Fitzgerald, G.F.;
Stanton, C. & Ross, R.P. (2004). Relative ability of orally administered Lactobacillus
murinus to predominate and persist in the porcine gastrointestinal tract. Applied and
Environmental Microbiology, 70, 1895–1906.
Gopinath, P.; Gogoi, S.K.; Chattopadhyay, A. & Gosh, S.S. (2008). Implications of silver
nanoparticle induced cell apoptosis for in vitro gene therapy. Journal of
Nanobiotechnology, 19, 075104.
Hahn, J.D. & Baker, D.H. (1993). Growth and plasma zinc responses of young pigs fed
pharmacologic levels of zinc. Journal of Animal Science, 71, 3020-3024.
Hedemann, M.S.; Jensen, B.B. & Poulsen, H.D. (2006). Influence of dietary zinc and copper
on digestive enzyme activity and intestinal morphology in weaned pigs. Journal of
Animal Science, 84, 3310-3320.
Hill, G.M.; Cromwell, G.L.; Crenshaw, T.D.; Dove, C.R.; Ewan, R.C.; Knabe, D.A.; Lewis,
A.J.; Libal, G.W.; Mahan, D.C.; Shurson, G.C.; Southern, L.L. & Veum, T.L. (2000).
Growth promotion effects and plasma changes from feeding high dietary
concentrations of zinc and copper to weanling pigs (regional study). Journal of
Animal Science, 78, 1010-1016.
Hogberg, O.; Canibe, N.; Poulsen, H.D.; Hedemann, M.S. & Jensen, B.B. (2005). Influence of
dietary zinc oxide and copper sulphate on the gastrointestinal ecosystem in newly
weaned piglets. Applied and Environmental Microbiology, 71, 2267-2277.
Hwang, M.G. ; Katayama, H. & Ohgaki, S. (2007). Inactivation of Legionella pneumophila and
Pseudomonas aeruginosa: evaluation of the bactericidal ability of silver cations. Water
Research, 41, 4097-4104.
Jensen, LS; Peterson, RP & Falen, L. (1974). Inducement of enlarged hearts and muscular
dystrophy in turkey poults with dietary silver. Poultry Science, 53, 57-64.
Jensen-Waern, M.; Melin, L.; Lindberg, R.; Johanisson, A.; Peterson, L. & Wallgren, P. (1998).
Dietary zinc oxide in weaned pigs-effects on performance, tissue concentrations,
morphology, meutrophil functions and faecal microflora. Research in Veterinary
Science, 64, 225-231.
Jung, W.K.; Koo, H.K.; Kim, K.W.; Shin, S.; Kim, S.H. & Park, Y.H. (2008). Antibacterial
activity and mechanism of action of the silver ion in Staphylococcus aureus and
Escherichia coli. Applied and Environmental Microbiology, 74, 2171-2178.
Kim, J.S.; Kuk, E.; Yu, K.N.; Kim, J.H.; Park, S.J.; Lee, H.J.; Kim, S.H.; Park, Y.K.; Park, Y.H.;
Hwang, C.Y.; Kim, Y.K.; Lee, Y.S.; Jeong, D.H. & Cho, M.H. (2007). Antimicrobial
effect of silver nanoparticles. Nanomedicine: Nanotecnology, Biology and Medicine, 3,
95-101.
Klasen, H.J. (2000). Historical review of the use of silver in the treatment of burns. I. Early
uses. Burns, 26, 117-130
Lam, P.K.; Chan, E.S.; Ho, W.S. & Liew, C.T. (2004). In vitro cytotoxicity testing of
nanocrystalline silver dressing (Acticoat) on cultured keratinocytes. British Journal
of Biomedical Science, 61, 125-127.
Lansdown, A.B. (2006). Silver in health care: antimicrobial effects and safety in use. Current
Problems in Dermatology, 33, 17-34.
Li, B. T.; Van Kessel, A. G.; Caine, W. R.; Huang, S. X. & Kirkwood, R. N. (2001). Small
intestinal morphology and bacterial populations in ileal digesta and feces of newly
weaned pigs receiving a high dietary level of zinc oxide. Canadian Journal of Animal
Science, 81, 511-516.
Li, Y.; Leung, P.; Yao, L.; Song, K.W. & Newton, E. (2006). Antimicrobial effect of surgical
masks coated with nanoparticles. Journal of Hospital Infection, 62, 58-63
Lok, C.N.; Ho, C.M.; Chen, R.; He, Q.Y.; Yu, W.Y.; Sun, H.; Tam, P.K.H.; Chiu, J.F. & Che,
C.M. (2006). Proteomic analysis of the mode of antibacterial action of silver
nanoparticles. Journal of Proteome Research, 5, 916-924.
Mull, A.J. & Perry, F.G. (2001). The role of fructo-oligosaccharides in animal nutrition. In
Recent developments in pig nutrition 3, J. Wiseman y P.C. Garnsworthy (eds.), pp. 79-
105, Nottingham University Press, Nottingham.
Partanen, K.H. & Mroz, Z. (1999) Organic acids for performance enhancement in pig diets.
Nutrition Research Reviews, 12, 117-145.
Percival, S.L.; Bowler, P.G. & Russell, D. (2005). Bacterial resistance to silver in wound care.
Journal of Hospital Infection, 60, 1-7.
Ravindran, V., Kornegay, E.T.,1993. Acidification of weaner pig diets: a review. Journal of
the Science of Food and Agriculture 62, 313-322.
Ricketts, C.R.; Lowbury, E.J.L.; Lawrence, J.C.; Hall, M. & Wilkins, M.D. (1970). Mechanism
of prophylaxis by silver compounds against infection of burns. British Medical
Journal, 2, 444-446.
Rungby, J. & Danscher, G. (1984). Hypoactivity in silver exposed mice. Acta Pharmacologica
Toxicologica, 55, 398-401.
Sawosz, E.; Binek, M.; Grodzik, M.; Zielinska, M.; Sysa, P.; Szmidt, M.; Niemec, T. &
Chwalibog, A. (2007). Influence of hydrocolloidal silver nanoparticles on
gastrointestinal microflora and morphology of enterocytes of quails. Archives of
Animal Nutrition, 61, 444-451.
Schreurs, W.J. & Rosenberg, H. (1982). Effect of silver ions on transport and retention of
phosphate by Escherichia coli. Journal of Bacteriology, 152, 7-13.
Singh, M.; Singh, S., Prasad, S. & Gambhir, I.S. (2008). Nanotechnology in medicine and
antibacterial effect of silver nanoparticles. Digest Journal in Nanomaterials and
Biostructures, 3, 115-122.
Smith, J.W.; Tokach, M.D.; Goodband, R.D.; Nelssen, J.L. & Richert, B.T. (1997). Effects of the
interrelationship between zinc oxide and copper sulfate on growth performance of
early-weaned pigs. Journal of Animal Science, 75, 1861-1866.
Sondi, I. & Salopek-Sondi, B. (2004). Silver nanoparticles as antimicrobial agent : a case study
on E. coli as a model for Gram-negative bacteria. Journal of Colloid Interface Science,
275, 177-182.
Spencer, R.C. (1999). Novel methods for the prevention of infection of intravascular devices.
Journal of Hospital Infection, 43, S127-S135.
Wadhera, A. & Fung, M. (2005). Systemic argyria associated with ingestion of colloidal
silver. Dermatology Online Journal 11, 12 (http://dermatology.cdlib.org/111).
Warriner, R. & Burrell, R.E. (2005). Infection and the chronic wound: a focus on silver.
Advances on Skin Wound Care, 18, 2-12.
Silver Nanoparticles334
Wright, J.B.; Lam, K. & Burrell, R.E. (1994). Wound management in an era of increasing
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... Many minerals are used as nanoparticles in animal research. These include aluminium (Li et al. 2011), calcium (Matuszewski et al. 2020a;Abdelnour et al. 2021;Abo El-Maaty et al. 2021), copper (Gonzales-Eguia et al. 2009;Miroshnikov et al. 2015;Mroczek-Sosnowska et al. 2014Refaie et al. 2015;Joshua et al. 2016;Ognik et al. 2016b;Scott et al. 2016;El Basuini et al. 2017;Tomaszewska et al. 2017;Scott et al. 2018;Aminullah et al. 2021;Morsy et al. 2021;Naz et al. 2021), gold (Sembratowicz et al. 2016;Sanati et al. 2019;Hassanen et al. 2020), iron (Pilaquinga et al. 2021), magnesium (Kesmati et al. 2016;Mazaheri et al. 2019;Abdelnour et al. 2021), nickel (Gong et al. 2016), selenium (Zhang et al. 2001(Zhang et al. , 2008Shi et al. 2011a;Wu et al. 2011;Sadeghian et al. 2012;Xun et al. 2012;El-Deep et al. 2016;Joshua et al. 2016;Muralisankar et al. 2016;Yaghmaie et al. 2017;Gangadoo et al. 2018Gangadoo et al. , 2020Hassan et al. 2020;Kojouri et al. 2020;Nabi et al. 2020;Sheiha et al. 2020;Han et al. 2021;Rana, 2021), silver (Grodzik and Sawosz 2006;Sawosz et al. 2007;Fondevila et al. 2009;Fondevila, 2010;Ahmadi and Rahimi 2011;Pineda et al. 2012;Kout-Elkloub et al. 2015;Ognik et al. 2016a;Conine and Frost 2017;Bąkowski et al. 2018;Abdelsalam et al. 2019; Kumar and Bhattacharya 2019;Dung et al. 2020;Abdelnour et al. 2021;Awaad et al. 2021;Bidian et al. 2021;Niemiec et al. 2021), titanium (Li et al. 2011) and zinc (Joshua et al. 2016;Swain et al. 2016;Hassan et al. 2017;Olgun and Yildiz 2017;Bąkowski et al. 2018;Othman et al. 2018;Bakhshizadeh et al. 2019;Yusof et al. 2019;Abdollahi et al. 2020;Kociova et al. 2020;Cui et al. 2021;Eskandani et al. 2021;Hidayat et al. 2021;Mahmoud et al. 2021;Ouyang et al. 2021;Szuba-Trznadel et al. 2021;El-Maddawy et al. 2022) nanoparticles. ...
... The effect of silver nanoparticles on animal productive performance, blood parameters, immune system, their accumulation in animals' organs and intestinal microbiome was summarized in the reviews of Fondevila (2010), Gangadoo et al. (2016), Bąkowski et al. (2018, etc. Since silver compounds are known for their antimicrobial properties, silver nanoparticles are considered as a potential antimicrobial feed additive (Grodzik and Sawosz 2006;Sawosz et al. 2007;Pineda et al. 2012;Ognik et al. 2016a;Kumar and Bhattacharya 2019;Youssef et al. 2019;Awaad et al. 2021;Niemiec et al. 2021). ...
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The application of high doses of mineral feed additives in the form of inorganic salts increases the growth performance of animals, but at the same, due to their low bioavailability, can contaminate the environment. Therefore, there is a need to find a replacement of administering high doses of minerals with an equally effective alternative. The application of lower doses of metal-containing nanoparticles with the same effect on animal production could be a potential solution. In the present review, zinc, silver, copper, gold, selenium, and calcium nanoparticles are discussed as potential feed additives for animals. Production of nanoparticles under laboratory conditions using traditional chemical and physical methods as well as green and sustainable methods-biosynthesis has been described. Special attention has been paid to the biological properties of nanoparticles, as well as their effect on animal health and performance. Nano-minerals supplemented to animal feed (poultry, pigs, ruminants, rabbits) acting as growth-promoting, immune-stimulating and antimicrobial agents have been highlighted. Metal nanoparticles are known to exert a positive effect on animal performance, productivity, carcass traits through blood homeostasis maintenance, intestinal microflora, oxidative damage prevention, enhancement of immune responses, etc. Metal-containing nanoparticles can also be a solution for nutrient deficiencies in animals (higher bioavailability and absorption) and can enrich animal products with microelements like meat, milk, or eggs. Metal-containing nanoparticles are proposed to partially replace inorganic salts as feed additives. However, issues related to their potential toxicity and safety to livestock animals, poultry, humans, and the environment should be carefully investigated.
... Nanoparticles are also less prone to deactivation and offer easier and greater absorption properties in the various body and mucus membranes. 20,21 Magnesium and manganese and their oxide forms have been explored for their antidiabetic potential; however, the nanoparticle form of magnesium oxide and manganese oxide have not been fully explored for their antidiabetic potential. In addition, the effect of MgO and MnO on thyroid profile has yet to be dissected in detail. ...
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Magnesium oxide (MgO) and manganese oxide (MnO) have been reported to be effective against Diabetes Mellitus (DM). However, their nanoparticulate form has not been evaluated for antidiabetic effect. MgO and MnO nanoparticles (15–35 nm) were synthesized and subsequently characterized by ultraviolet-visible spectroscopy (UV-VIS), zeta sizer, and scanning electron microscopy. 6–7 weeks old rats weighing 200–220 mg were divided into 07 equal groups (n = 8), namely, negative control (NC), positive control (PC), standard control (Std-C), MgO high dose group (MgO-300) and low dose group (MgO-150), and MnO nanoparticle high dose (MnO-30) and low dose group (MnO-15). Diabetes was chemically induced (streptozotocin 60 mg/kg B.W) in all groups except the NC. Animals were given CMD and water was ad libitum. Nanoparticles were supplemented for 30 days after the successful induction of diabetes. Blood and tissue samples were collected after the 30 th day of the trial. The mean serum glucose, insulin, and glucagon levels were improved maximally in the MgO-300 group followed by MgO-150 and MnO-30 groups. Whereas the MnO-15 group fails to show any substantial improvement in the levels of glucose, insulin, and glucagon as compared to the positive control group. Interesting the serum triiodothyronine, thyroxine, and thyroid-stimulating hormone levels were markedly improved in all the nanoparticle treatment groups and were found to be similar to the standard control group. These results highlight the modulatory properties of MgO and MnO nanoparticles and merit further studies delineating the molecular mechanisms through which these nanoparticles induce antidiabetic effects.
... However, although the organic forms of these last elements are still greater as food additives in animal feed [12], the inorganic forms have disadvantages such as considerable tissue retention and being potentially contaminating [13]. Following this line of action, silver was used as an additive in chicken feed in the 1950s, but due to its high manufacturing cost, it was no longer used [14]. Currently, and due to the technological development of industrial nanoparticle manufacturing processes, silver nanoparticles (AgNPs) are of special interest [15]. ...
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According to the search for alternatives to replace antibiotics in animal production suggested in the antimicrobial resistance action plans around the world, the objective of this work was to evaluate the bactericidal effect of kaolin–silver nanomaterial for its possible inclusion as an additive in animal feed. The antibacterial activity of the C3 (kaolin–silver nanomaterial) product was tested against a wide spectrum of Gram-negative and Gram-positive bacteria (including multidrug resistant strains) by performing antibiograms, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), as well as growth inhibition curves against seven strains causing infections in animals. The C3 product generated inhibition halos in all the tested strains, and a higher activity against Gram-negative bacteria was found, with MBC values ranged from 7.8 µg/mL (P. aeruginosa) to 15.6 µg/mL (E. coli and Salmonella). In contrast, it was necessary to increase the concentration to 31.3 µg/mL or 250 µg/mL to eliminate 99.9% of the initial population of S. aureus ATCC 6538 and E. faecium ATCC 19434, respectively. Conversely, the inhibition growth curves showed a faster bactericidal activity against Gram-negative bacteria (between 2 and 4 h), while it took at least 24 h to observe a reduction in cell viability of S. aureus ATCC 6538. In short, this study shows that the kaolin–silver nanomaterials developed in the framework of the INTERREG POCTEFA EFA183/16/OUTBIOTICS project exhibit antibacterial activity against a wide spectrum of bacteria. However, additional studies on animal safety and environmental impact are necessary to evaluate the effectiveness of the proposed alternative in the context of One Health.
... Nanotechnology offers a possible solution to the problem, as commercially available methods such as antibiotics have failed to counter the problem due to the emergence of resistance in bacterial pathogens. Colloidal silver has been used since the early 1950s as an additive in animal feed and showed improved growth and reduction in infections, yet the use of colloidal silver was stopped and replaced with a cheaper alternative known as antibiotics [88]. In recent years, in vitro research has been done on the use of AgNPs to kill pathogenic bacterial cells and as a feed additive for antibacterial effects to promote animal growth. ...
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Nanotechnology is a rapidly developing field due to the emergence of various resistant pathogens and the failure of commercial methods of treatment. AgNPs have emerged as one of the best nanotechnology metal nanoparticles due to their large surface-to-volume ratio and success and efficiency in combating various pathogens over the years, with the biological method of synthesis being the most effective and environmentally friendly method. The primary mode of action of AgNPs against pathogens are via their cytotoxicity, which is influenced by the size and shape of the nanoparticles. The cytotoxicity of the AgNPs gives rise to various theorized mechanisms of action of AgNPs against pathogens such as activation of reactive oxygen species, attachment to cellular membranes, intracellular damage and inducing the viable but non-culturable state (VBNC) of pathogens. This review will be centred on the various theorized mechanisms of actions and its application in the aquaculture, livestock and poultry industries. The application of AgNPs in aquaculture is focused around water treatment, disease control and aquatic nutrition, and in the livestock application it is focused on livestock and poultry.
Article
We evaluated the fects of different levels of dietary silver nanoparticle (AgNP) powder on performance, intestinal microflora, carcass traits and blood parameters of broiler chickens. Three hundred seven-day-old Ross broiler chicks were randomly divided into five groups, each group replicated three times with 20 birds per replication. Chickens were fed the basal diet with 2.5, 5, 10 and 20 mg AgNPs per kg feed. Dietary inclusion of AgNPs improved the final body weight, cumulative weight gain and feed conversion ratio. The best broiler performance, carcass traits, and relative organ weights were observed in the group supplemented with 2.5 ppm AgNPs. Increasing the AgNP dose resulted in a significant decrease in the caecal lactose positive and enterococci bacteria populations, while lactobacilli counts were numerically increased. The silver residues in the breast and thigh muscle significantly increased (p <.05) in a dose-dependent manner. Dietary inclusion of AgNPs induced dose-dependent lesions in liver, kidney, spleen and duodenum tissues involving degeneration, necrosis, mononuclear infiltration and focal aggregation of inflammatory cells. In conclusion, despite its potential positive impacts on growth performance, carcass traits and caecal microbial population diversity at a dose of 2.5 ppm, dietary inclusion of AgNPs had the following negative effects on broilers: 1) silver residues in breast and thigh muscle, which may result in AgNPs transmission to consumers, and 2) cytotoxicity in intestinal, liver, spleen and kidney cells in a dose-dependent manner. Therefore, we suggest the use of lower doses of AgNPs (< 2.5 ppm diet) in poultry production in the future studies.HIGHLIGHTS Dietary inclusion of silver nanoparticles (AgNPs) in broiler diets more than 2.5 mg/kg diets had many negative effects represented by accumulation of silver residue in broiler meat and the possibility of transmission of nanosilver to consumers. AgNPs had a cytotoxic effect on intestine, liver, spleen and kidney cells in a dose-dependent manner in broilers and might be harmful to chicken and human health. Therefore, we do not recommend using AgNPs as a dietary growth promotor or antibacterial agent in broiler diets and their use and marketing should be controlled and restricted. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Chapter
In the 1980s, nanotechnology has started showing its potential in the multidisciplinary field of study and paced with the emerging techniques to see things clearly at the nanoscale. After four decades of intensive research and dedicated nanoscience, nanoparticles and nanomaterials is omnipresent right from the electronic gadget to food science. Globally, the repercussions of using nanomaterials were reported and verified by scientific communities. Nanomaterials' impact as nano-toxic nano-waste is critical and needs to be addressed through international legislation and regulations. Scanty and fragmented information is available on the regulation guidelines and legislations. This study highlighted the application, impact and potentials threats of nanomaterials and nanoparticles. Furthermore, we tried to cover global regulations and legislation to safeguard the environment and human health. Critical impact analysis with comprehensive and well-designed laws concomitant with strict legislation will undoubtedly eradicate mall practice and non-judicious use of nanoparticles and nanomaterials. Nanoparticles widen the scope of paradigm shift from exhaustive resource technologies to resource-efficient nanotechnologies leading to sustainable development.
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Escherichia coli infection is considered one of the most economically important multi-systemic diseases in poultry farms. Several nanoparticles such as silver, chitosan and copper oxide are known to be highly toxic to several microbes. However, there are no data concerning their success against in vivo experimental E. coli infection in broilers. So that, this study was designed to investigate the bactericidal effect of low doses of CuO-NPs (5mg/kg bwt), Ag-NPs (0.5mg/kg bwt) and Ch-Ag NPs (0.5mg/kg bwt) against E. coli experimental infection in broilers. One hundred chicks were divided in to 5 groups as the following: (1) control; (2) E. coli (4x108 CFU\ml) challenged; (3) E. coli +CuO-NPs; (4) E. coli +Ag-NPs; (5) E. coli +Ch-Ag NPs. The challenged untreated group, not NPs treated groups, recorded the lowest weight gain as well as the highest bacterial count and lesion score in all examined organs. The highest liver content of silver was observed in Ag-NPs treated group compared with the Ch-Ag NPs treated group. Our results concluded that Ch-Ag NPs not only had the best antibacterial effects but also act as a growth promoter in broilers without leaving any residues in edible organs. We recommend using Ch-Ag NPs in broiler farms instead of antibiotics or probiotics.
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A study was carried out to determine the effect of dietary supplementation of 3000 mg kg(-1) zinc oxide (ZnO) on the small intestinal morphology and populations of enterobacteriaceae, lactobacilli and clostridia in ileal digesta and feces of weaned pigs. At 17 d of age, 36 pigs from nine litters were fitted with simple T-cannulae at the distal ileum and after a 2-h post-surgery recovery returned to their sows. At 21 d of age, the pigs were weaned and housed in individual metabolism crates. Pigs were allocated to receive a standard starter diet supplemented with or without 3000 mg kg(-1) of ZnO. Beal digesta and fecal samples were collected immediately before weaning and then on days 2, 4, 7, 9, and 11 after weaning and were used to quantify enterobacteriaceae, lactobacilli and clostridial populations by colony enumeration on selective media. Pigs were euthanized following the final sampling, and 2cm sections of tissue were collected from sites 25, 50 and 75% along the length of the small intestine for determination of mucosal thickness (MT), crypt depth (CD), villous height (VH) and villous width (VW). Zinc oxide supplementation altered the mucosal morphology of the small intestine. Mucosal thickness (P < 0.08) and VH (P < 0.05) were increased at sites 25 and 50% along the length of the small intestine by ZnO supplementation. Overall VW also increased (P < 0.01) with ZnO supplementation. Crypt depth decreased (P < 0.05) at 75% along the length of the small intestine with ZnO supplementation. The ratio of VH to CD was higher (P < 0.05) for ZnO-supplemented than for control-fed pigs at sites 25, 50 and 75% along the length of the small intestine. There was no effect (P > 0.05) of supplementary ZnO on bacterial populations in ileal digesta or feces. The present study indicates that supplementing ZnO in starter diets changes the epithelial morphology of the small intestine, which may affect nutrient digestion and absorption in newly weaned pigs.
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Nanotechnology is expected to open some new aspects to fight and prevent diseases using atomic scale tailoring of materials. The ability to uncover the structure and function of biosystems at the nanoscale, stimulates research leading to improvement in biology, biotechnology, medicine and healthcare. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. The integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug delivery vehicles. In all the nanomaterials with antibacterial properties, metallic nanoparticles are the best. Nanoparticles increase chemical activity due to crystallographic surface structure with their large surface to volume ratio. The importance of bactericidal nanomaterials study is because of the increase in new resistant strains of bacteria against most potent antibiotics. This has promoted research in the well known activity of silver ions and silver-based compounds, including silver nanoparticles. This effect was size and dose dependent and was more pronounced against gram-negative bacteria than gram-positive organisms.
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An experiment was conducted to compare the efficacy of two Zn sources, zinc oxide (ZnO) and tetrabasic zinc chloride (TBZC) in the diet at pharmacological doses to promote growth of the weanling piglet for 28 days. One hundred and eighty weanling piglets averaged 7.5kg of body weight (BW) were assigned to six dietary treatments. The six dietary treatments were as following: no supplementation of Zn (control); supplemental Zn at 2250mg/kg diet from ZnO; supplemental Zn at 3000mg/kg diet from ZnO; supplemental Zn at 1500mg/kg diet from TBZC; supplemental Zn at 2250mg/kg diet from TBZC; and supplemental Zn at 3000mg/kg diet from TBZC. The results showed that average daily growth (ADG) and average daily feed intake (ADFI) responded quadratically as the dietary supplementation of TBZC or ZnO increased. Feed conversion efficiency responded quadratically in the case of TBZC. Feeding pharmacological Zn from ZnO or TBZC improved growth performance of weanling piglet for the first 4 weeks after weanling. Feeding supplemental Zn from two Zn sources increased plasma and tissue (liver, kidney, and metacarpal) Zn concentrations linearly (P0.01). Based on plasma Zn concentrations at week 2 or 4 of the experiment, and liver, kidney, metacarpal Zn concentrations at week 4 of the experiment, relative bioavailability (RBV) of Zn in TBZC was 159%, 125%, and 128%, 123%, 122%, respectively, compared to ZnO.
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The potential of diet acidification to overcome the digestive insufficiency and postweaning lag in early weaned pigs is examined in the review. A survey of published data on various types of acidifiers reveal considerable variation in response to acidification of weaner diets. Several reasons may be proposed to explain the inconsistencies in response, these include differences in diet type, age of pigs, type and level of acidifier, and existing performance levels. Reducing the gastric pH does not appear to be the primary effect of acidifiers. Acidification, however, consistently suppressed pathogenic coliforms in the gastrointestinal tract. Future developments in the use of acidifiers would be intrinsically linked to the understanding of their mode(s) of action in the animal.
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Organic acids and their salts appear to be potential alternatives to prophylactic in-feed antibiotics and growth promoters in order to improve the performance of weaned piglets, fattening pigs and reproductive sows, although their growth-promoting effects are generally less than that of antibiotics. Based on an analysis of published data, the growth-promoting effect of formates, fumarates and citrates did not differ in weaned piglets. In fattening pigs, formates were the most effective followed by fumarates, whereas propionates did not improve growth performance. These acids improved the feedgain ratio of both weaned piglets and fattening pigs. In weaned piglets, the growth-promoting effects of dietary organic acids appear to depend greatly on their influence on feed intake. In sows, organic acids may have anti-agalactia properties. Successful application of organic acids in the diets for pigs requires an understanding of their modes of action. It is generally considered that dietary organic acids or their salts lower gastric pH, resulting in increased activity of proteolytic enzymes and gastric retention time, and thus improved protein digestion. Reduced gastric pH and increased retention time have been difficult to demonstrate, whereas improved apparent ileal digestibilities of protein and amino acids have been observed with growing pigs, but not in weaned piglets. Organic acids may influence mucosal morphology, as well as stimulate pancreatic secretions, and they also serve as substrates in intermediary metabolism. These may further contribute to improved digestion, absorption and retention of many dietary nutrients. Organic acid supplementation reduces dietary buffering capacity, which is expected to slow down the proliferation and|or colonization of undesirable microbes, e.g. Escherichia coli, in the gastro-ileal region. However, reduced scouring has been observed in only a few studies. As performance responses to dietary organic acids in pigs often varies, more specific studies are necessary to elucidate an explanation.
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Three experiments were carried out in order to determine the potential of silver nanoparticles as an additive in diets for weanling pigs. In Experiment 1, ileal contents of 4 pigs weaned 7 days before were incubated in vitro for 4h at 37°C with 0, 25, 50 and 100μgAg/g. Metallic silver (in colloidal form) linearly reduced coliforms (P=0.003) and lactobacilli (P=0.041) concentration, but did not affect the lactobacilli proportion compared with the control. In Experiment 2, three groups of 5 weaned pigs were given a diet with 0, 20 or 40mgAg/kg. The second week after weaning daily growth of pigs increased linearly (P=0.007) with the dose of silver nanoparticles. A trend (P=0.073) for a linear reduction in the ileal concentration of coliforms was observed by culture counts, but lactobacilli remained unaffected. There were no differences among treatments in the ileal concentration of coliforms or lactobacilli measured by FISH. However, the concentration of total bacteria (P=0.010) and Atopobium (P=0.001) decreased at a decreasing rate. No differences were detected in the other bacterial groups tested, except for a lowest concentration of the Clostridiumperfringens/Clostridiumhistolyticum group in 20mgAg/kg (P=0.012). No treatment effect was detected in histological examination of ileal mucosa. In Experiment 3, productive performance and silver retention in tissues with 0, 20 or 40mgAg/kg diet were studied with 6 lots of 4 piglets per treatment in five weeks after weaning. Feed intake was highest in treatment with 20mgAg/kg (P
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The impact of manufactured nanomaterials on human health and the environment is a major concern for commercial use of nanotechnology based products. A judicious choice of selective usage, lower nanomaterial concentration and use in combination with conventional therapeutic materials may provide the best solution. For example, silver nanoparticles (Ag NPs) are known to be bactericidal and also cytotoxic to mammalian cells. Herein, we investigate the molecular mechanism of Ag NP mediated cytotoxicity in both cancer and non-cancer cells and find that optimum particle concentration leads to programmed cell death in vitro. Also, the benefit of the cytotoxic effects of Ag NPs was tested for therapeutic use in conjunction with conventional gene therapy. The synergistic effect of Ag NPs on the uracil phosphoribosyltransferase expression system sensitized the cells more towards treatment with the drug 5-fluorouracil. Induction of the apoptotic pathway makes Ag NPs a representative of a new chemosensitization strategy for future application in gene therapy.
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Nanosilver is increasingly used in the food industry and biomedical applications. A lot of studies have been done to investigate the potential toxicity of nanosilver. But information on whether or how nanosilver particles bring changes in genetic materials remains scant. In this study, the replication fidelity of the rpsL gene was quantified when nanosilver particles were present in polymerase chain reactions (PCRs) or cell cultures of E. coli transformed with the wild-type rpsL gene. Three types of nanosilver (silver nanopowder, SN; silver-copper nanopowder, SCN; and colloidal silver, CS) were tested. The results showed that the replication fidelity of the rpsL gene was differentially compromised by all three kinds of nanosilver particle compared with that without nanosilver. This assay could be expanded and applied to any other materials to preliminarily assess their potential long-term toxicity as a food additive or biomedical reagent. Moreover, we found that nanosilver materials bind with genomic DNA under atomic force microscopy, and this might be an explanation for the compromised DNA replication fidelity.