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Context: The pathogenesis of renal damage as a risk factor of renal failure can be due to oxidative stress resulting from an imbalance between the production of free radicals and antioxidants. Therefore, antioxidant therapy can be a good strategy to decrease the effects of such diseases. Hence, the aim of this review was to evaluate the protective effect of olive oil as an herb rich in antioxidant compounds on kidney damage in previous studies. Evidence Acquisitions: Present review is based on scrutinizing the contents of relevant papers searched in PubMed, Google Scholar, EBSCO, Embase, directory of open access journals (DOAJ), Web of Science and Scopus. Results: Numerous studies have introduced herbal treatments, being rich sources of antioxidants, as appropriate alternatives for several diseases, including renal damage, when considering the pathogenesis of the diseases. The olive has also been recommended as a plant that has different therapeutic effects, and its therapeutic effects on the kidneys are mentioned in several studies, including the reduction of renal damage parameters and an increase in the antioxidant power of enzymes in the body. Conclusions: Considering the numerous studies on animal models, particularly rats and renal cell lines, olive oil can be used as a reliable method for the treatment of various kidney damages. However, further studies are also recommended in humans.
Protective effects of olive in renal failure; a review on current
knowledge doi: 10.15171/jnp.2019.02 J Nephropathol. 2019;8(1):e02
Journal of Nephropathology
*Corresponding author : Reza Mohammadrezaei Kkorramabadi;
Esmaeel Babaeenezhad1,2
, Hassan Ahmadvand2,3, Reza Mohammadrezaei Kkorramabadi3*, Shahrokh
Bagheri3, Peyman Khosravi3, Parisa Jamor4
1Department of Cardiology, Madani Heart Center, Lorestan University of Medical Sciences, Khorramabad, Iran
2Department of Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
3Razi Herbal Researches Center, Lorestan University of Medical Sciences, Khorramabad, Iran
4Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
Article type:
Article history:
Received: 14 February 2018
Accepted: 10 June 2018
Published online: 29 June 2018
Oxidative stress
Renal failure
Context: The pathogenesis of renal damage as a risk factor of renal failure can be due to oxidative
stress resulting from an imbalance between the production of free radicals and antioxidants.
Therefore, antioxidant therapy can be a good strategy to decrease the effects of such diseases. Hence,
the aim of this review was to evaluate the protective effect of olive oil as an herb rich in antioxidant
compounds on kidney damage in previous studies.
Evidence Acquisitions: Present review is based on scrutinizing the contents of relevant papers searched
in PubMed, Google Scholar, EBSCO, Embase, directory of open access journals (DOAJ), Web of
Science and Scopus.
Results: Numerous studies have introduced herbal treatments, being rich sources of antioxidants,
as appropriate alternatives for several diseases, including renal damage, when considering the
pathogenesis of the diseases. The olive has also been recommended as a plant that has different
therapeutic effects, and its therapeutic effects on the kidneys are mentioned in several studies,
including the reduction of renal damage parameters and an increase in the antioxidant power of
enzymes in the body.
Conclusions: Considering the numerous studies on animal models, particularly rats and renal
cell lines, olive oil can be used as a reliable method for the treatment of various kidney damages.
However, further studies are also recommended in humans.
Implication for health policy/practice/research/medical education:
Today, the need for plant derived compounds to treat diseases is felt more and more due to the lower side effects. On the other
hand, studies have shown that medicinal plants, especially olives, have an effect on kidney disease.
Please cite this paper as: Babaeenezhad E, Ahmadvand H, Mohammadrezaei Kkorramabadi R, Bagheri S, Khosravi P, Jamor
P. Protective effects of olive in renal failure; a review on current knowledge. J Nephropathol. 2019;8(1):e02. doi: 10.15171/
1. Context
The pathogenesis of renal damage as a risk factor of renal
failure can be due to oxidative stress resulting from an
imbalance between the production of free radicals and
antioxidants (1). Therefore, antioxidant therapy can be
a good strategy to protect the renal damage from free
radi cals (1). Many studies showed that olive oil, olive leaf
and olive fruit and their compounds such as oleuropein,
hydroxytyrosol, and oleic acid have antioxidant and anti-
inflammatory activities (2).
2. Evidence Acquisitions
For this review, we used a variety of sources by searching
through PubMed/Medline, Scopus, EMBASE, EBSCO,
Embase and Directory of Open Access Journals (DOAJ).
The search was conducted, using combinations of the
following key words and or their equivalents; Olive,
Oxidative stress and Renal failure
Babaeenezhad et al
Journal of Nephropathology, Vol 8, No 1, January 2019
3. Protective effects of olive and its various
compositions on renal failure
3.1. Protective effects of olive or its various compositions on
drug induced nephrotoxicity
3.1.1. Doxorubicin
The antitumor effect of doxorubicin has been introduced
for the selection of this compound in order to deal with a
range of cancers, such as leukemia, lymphoma, and solid
tumors in humans (3). However, the limiting factor in
the use of doxorubicin in the treatment of cancer is its
toxic effects on vital organs, such as the heart, kidneys,
and liver (4, 5). One of the main damaging mechanisms
of this drug to various tissues including the heart, liver,
and kidneys is related to the oxidative stress and reduction
of antioxidants, and also increased oxidants in particular
reactive oxygen species (6). Hence, there is a requirement
to deal with oxidative stress and antioxidant compounds,
in particular administration of herbal medicines. The
beneficial effects of the olive plant were evaluated in the
study conducted by Kumral and colleagues as an herbal
remedy containing multiple antioxidant compounds (7).
Kumral et al proved that the use of olive leaf ethanol
extract, at the same time as doxorubicin on rats, reduces
serum urea compared with a group which was treated
only with doxorubicin (8). The results showed that the
ethanol extract of olive leaves reduced malondialdehyde
(MDA), protein carbonyl, and conjugated diene, while it
also increased superoxide dismutase (SOD), glutathione
(GSH), and GSH peroxidase in the kidneys (8). Today,
antibiotics as antimicrobial agents are administered in the
treatment of infections. The side effects of antibiotics,
especially gentamicin sulfate, an antibiotic from the
aminoglycosides group, have created restrictions on the
use of this drug. The most well-known side effect of this
anti-gram-negative bacteria antibiotic is nephrotoxicity
The improvement of nephrotoxicity associated with the
drug has been the subject of numerous research studies. In
one study, it was shown that treatment of nephrotoxicity
induced by gentamicin using ethanol extract of the olive
leaf had a remediation effect in rats (12). Additionally, it
was shown that ethanol extract of the olive leaf reduced
creatinine, urea, and MDA, and also increased serum
GSH, and activities of catalase (CAT) and SOD (12).
In addition, the glomerular volume in the group of rats
treated with gentamicin and treated olive leaf extract
decreased, compared to the group treated only with
gentamicin (12). In addition, using a combination of
gentamicin and olive oil, this led to a reduction of urea
and serum creatinine compared to the group treated only
with gentamicin (12).
3.1.2. Cisplatin
Despite limitations in the use of cisplatin due to its
side effects, in particular, nephrotoxicity, neurotoxicity,
ototoxicity, nausea and vomiting, the drug is still
considered as one of the most powerful drugs
administered in cancer chemotherapy for testicular,
ovarian, neck cervical, head and neck cancers (13). The
role of oxidative stress and free radicals has been proven
in the nephrotoxicity of cisplatin. In a study, it was shown
that olive leaf extract reduced serum creatinine compared
with the group treated with cisplatin (13).
3.1.3. Cyclosporine
Renal complications induced by cyclosporine A
consumption have been proven in the treatment of
transplant rejection and autoimmune diseases that
suppress the immune system. Around 30% of patients
treated with the drug are influenced by the resultant
kidney complications. Acute and chronic nephrotoxicity
can be defined as renal complications of this drug (14).
The production of free radicals and oxidative stress are
the mechanisms of creating renal damages by this drug
(14). Another mechanism caused as a result of this
drug is kidney damage. Other mechanisms involved in
renal complications arising from the consumption of
this drug include; activation of the renin-angiotensin
system, increased activity of the sympathetic nervous
system, increase in endothelium synthesis, induction
of cytochrome P450 enzymes in renal microsomes, and
vasoconstriction (15). Mostafa-Hedeab et al showed
that the treatment given to rats with olive leaf extract
improved renal toxicity induced by cyclosporine (14).
The use of olive leaf extract increased the amount of
GSH and activities of GSH, CAT, and SOD compared
to the group treated with cyclosporine (14).
The mechanism of action of 2,4-dichlorophenoxyacetic
acid can be justified as an herbicide by disrupting cell
division and protein synthesis and overall production of
oxygen-free radicals (16).
In the research conducted by Nakbi et al, the treatment
of male rats given 2,4-dichlorophenoxyacetic acid was
studied using hydrophilic and lipophilic compounds
of olive oil (16). It was shown that renal marker levels,
including creatinine, urea, albumin, and uric acid,
were recovered due to their synergistic effects of these
compounds. MDA levels were also improved in the group
treated with olive oil. Activities of antioxidant enzymes
such as CAT, superoxide (SOD) and GSH peroxidase in
the group treated with olive oil increased when compared
to the group given 2,4-dichlorophenoxyacetic acid, the
same as the control group (16,17). Histologically, the
group treated with olive oil compared to the groups Journal of Nephropathology, Vol 8, No 1, January 2019
Protective effects of olive in renal failures
treated with combinations of hydrophilic and lipophilic
compounds had a significant recovery rate in relation
to glomerulus atrophy, the tubular expansion, vascular
and tissue congestion, degeneration tubular, and necrosis
caused by 2,4-dichlorophenoxyacetic acid (16,17).
3.1.4. Carbon tetrachloride
Carbon tetrachloride is often known as a poison that
affects the liver. Cytochrome P450, as a liver enzyme,
converts this toxin into the CCl3 and Cl radicals (18).
The obtained CCl3 from this toxin as a free radical
eventually targets the lipid membrane of endoplasmic
reticulum (19). A study on improving the effects of
olive leaf extract on nephrotoxicity induced by carbon
tetrachloride in rats revealed that olive leaf extract,
especially in a dose of 100 mg per kg (20), leads to
reduced urea and creatinine in the treated groups using
this extract, and an increase in serum uric acid with the
same level as the control group. The activity of enzymes
including SOD, CAT and GSH levels also increased,
while the activity of MDA, decreased in terms of the
antioxidant system. Histological studies also revealed
improvements in the group treated with olive leaf extract
3.1.5. Amikacin
Amikacin is widely used as an antibiotic of the
aminoglycoside group in the treatment of infections
caused by gram-negative bacteria (21). Today, the use
of this antibiotic has been limited due to its proven
toxic effects on the kidneys and side effects, such as
tubular necrosis, in several studies on animal and human
models. The production of oxygen-free radicals, similar
to other aminoglycosides, is the main mechanism
of nephrotoxicity developed by consumption of this
aminoglycoside (22). Various studies, including the
study of Abdel-Gayoum and colleagues, on improving
the effects of olive oil and leaf extract on nephrotoxicity-
induced amikacin in rats have shown that the amount
of creatinine and urea decreased in those groups treated
with olive oil and olive leaf extract, particularly olive oil
compared to the control group. Histological studies also
showed improvements in the treatment groups (23).
3.1.6. Thioacetamide
Thioacetamide can be viewed as a hepatic toxin and
carcinogen (24). The toxic complications of this
compound are not only limited to the liver, but involve
several organs such as the kidneys, spleen, lungs,
intestines, and brain (24,25). Al-Attar et al studied the
protective effects of olive leaf extract on nephrotoxicity of
this substance in the kidneys of mice and proved that the
levels of urea and serum creatinine in the group treated
with olive leaf extract reduced, but not significantly.
In terms of histological, the normality of the kidney
structure was proved in the group treated with the extract
3.1.7. Chromium
Extensive use of chrome in the industry is expanding. The
complications of dealing with this compound on humans
are classified in a variety of types such as nephrotoxicity,
hepatic toxicity, and carcinogenicity (26, 27). A study by
Saber and colleagues looked at improving the effects of
pure olive oil on nephrotoxicity induced by chromium in
rats and revealed that olive oil reduced urea, creatinine,
and MDA, while it increased SOD, CAT, and GSH in
rats poisoned with chromium (27).
3.1.8. Mercuric chloride
Adverse effects of mercury chloride on human health,
especially the kidneys, have been proven in various studies
(28). Suggested mechanisms for the traumatic effect of
this toxic substance are lipid peroxidation and hydrogen
peroxide production in the mitochondria of renal cells
(28). A study conducted by Necib et al on the protective
effects of olive oil in renal dysfunction and oxidative
stress induced by mercury chloride in rats demonstrated
that treatment using olive oil reduced the IL1, IL6,
TNFα, urea, creatinine, and uric acid, while it increased
MDA and GSH, GSH-PX, and GST (28, 29). Acute
kidney injury can be as a result of some form of renal
ischemia-reperfusion. Heart failure, heart attack, kidney
transplant, nephrectomy, and hemorrhagic shock are the
main causes of renal ischemia-reperfusion (30). Damage
to the kidneys through the renal ischemia-reperfusion
can be related to oxidative stress and the production of
free radicals, particularly reactive oxygen species (30). In
a research, improving the effect of olive leaf extract was
investigated on renal ischemia-reperfusion, and it was
found that olive leaf extract reduced urea, creatinine,
and serum MDA and increased GSH levels. Tubular
necrosis in the groups treated with olive leaf extract was
significantly increased compared to the untreated group.
The inner diameter of near tubules and the amount of
casts in all groups treated with olive leaf extract were
significantly reduced (30).
3.2. Protective effects of olive and its various compositions
on kidney stones
A high incidence of kidney stones in all societies has
been observed as being a problem for public health. An
aggregation of calcium oxalate crystals causes calcium
oxalate stones, which are the most common type of kidney
Babaeenezhad et al
Journal of Nephropathology, Vol 8, No 1, January 2019
stones. The excretion of most kidney stones is performed
without pain. However, sometimes these stones are cause
of obstructions. Hence, the administration of herbs in
their treatment can be very useful. The effect of olive
oil on the treatment of kidney stones has also been
analyzed in some studies (31). Herbal preparations affect
the kinetic factors of calcium oxalate crystallization in
synthetic urine: implications for kidney stone therapy
3.3. Protective effects of olive and its some compositions on
lupus erythematosus
Lupus erythematosus is an autosomal disease that is more
common in women compared to men. This autoimmune
disease is caused by the spontaneous reaction of the
immune system, particularly lymphocytes with the
body’s own tissues (32). One of the tissues involved in
these diseases is the kidney, but its exact involvement
mechanism is not well understood. Aparicio-Soto et
al concluded in their study that female mice poisoned
with Peristan, as animal models of systemic lupus
erythematosus treated using olive oil, saw improved
kidney damage through the activation of the HO-1/
Nrf-2 antioxidant pathway, and repression activation
of JAK/STAT, NF-Κb, and MAPK-induced by lupus
erythematosus (33).
4. Some important chemical compositions of olive and
protective effects on renal injury and other diseases
4.1. Oleuropein
The most abundant phenolic compounds in the leaves
of tree are oleuropein with its bitter taste (8, 34). The
antimicrobial effects of this compound against bacteria,
viruses, retrovirues, fungi, yeast, and yeast have been
proven (35). In addition, the inhibition effect of oleuropein
on platelet aggregation and eicosanoid production affect
the following: prevention of heart disease, improvement
of lipid metabolism, obesity, cancer, antioxidant, anti-
inflammatory, anti-atrophic, liver protective, anti-aging
nervous system, and skin protector (8,35-37). A study
by Mahmoudi et al showed the protective effect of
oleuropein on the kidneys of lactating rats affected by
Bisphenol A (38). The results showed that, in mother
and baby groups treated with the phenolic compounds,
the urea and serum creatinine returned to normal
levels, while the MDA level decreased significantly. A
significant increase in the amount of CAT and total
antioxidant capacity was observed in the groups treated
with oleuropein. Histologically, the glomerular necrosis
decreased especially in near and far twisted tubules in
the groups treated with oleuropein. Ahmadvand et al
studied the effects of oleuropein on lipid peroxidation,
lipid profile, atherogenic index, and paraoxonase 1 in
rats. Nephrotoxicity in rats using gentamicin revealed
a significant decrease in level of MDA, triglycerides,
cholesterol, LDL-C, VLDL and atherogenic index in the
groups treated with oleuropein. In contrast, oleuropein
additionally increased level of HDL-C and PON1
(paraoxonase 1) activity in treated group (8,37,39). In
another study on the protective effects of oleuropein
against cisplatin-induced nephrotoxicity in mice
animal models, it was found that oral administration of
oleuropein, particularly in a dose of 20 mg/kg, reduced
urea and serum creatinine (8). Coping with oxidative
stress, inflammation, decreased apoptosis, and inhibition
of MAPK/ERK pathway signaling pathways, suppression
of other signaling pathways, including MAPK and the
inhibition of ERK, are among the additional effects
of oleuropein in order to improve the nephrotoxicity
damage induced by cisplatin (40).
In another study on the antioxidant effects of oleuropein
in the treatment of renal failure caused by bacterial
lipopolysaccharide, it was shown that the levels of urea
and creatinine decreased in those groups treated with
oleuropein. The parameters of antioxidant enzymes such
as SOD, CAT and GPX also increased in the group
treated with oleuropein. Histological studies showed the
healing effects of this substance (8,34,41).
4.2. Oleic acid
Seventy-two percent of olive oil is formed from a
monounsaturated fatty acid called oleic acid (42). A
double bond in this fatty acid gives some advantages
over olive oil, such as its antioxidant properties (42).
Various anti-cancer therapeutic effects of this fatty acid
on chemical protection have been proven in a range
of cancers such as colorectal and breast cancer (42). In
one study, the effect of nitro-oleic acid was proven in
renal ischemia-reperfusion (43). In this study, plasma
urea and creatinine, tissue myeloperoxidase (MPO), the
expression of inflammatory factors and cytokines, renal
oxidative stress, and tissue damage of the kidneys in mice
treated with nitro-oleic acid decreased compared to renal
ischemia-reperfusion (43). In another study, the effect
of oleic acid was investigated on the growth of monkey
kidney cells. In this study, it was proved that 10 to 20 µg/
ml of oleic acid can be used as a supplement to cell growth
in serum replaced by MK2. However, levels higher than
20µg can cause an inhibition of cell growth (44).
4.3. Hydroxytyrosol
Hydroxytyrosol as a simple phenolic compound comprises
a major part of phenolic compounds in olive oil (45). This
combination is obtained from hydrolysis of secoiridoids, Journal of Nephropathology, Vol 8, No 1, January 2019
Protective effects of olive in renal failures
such as oleuropein and oligodendrocyte (45). The
highest antioxidant activity of phenolic compounds in
olive oil can be attributed to hydroxytyrosol. The reason
for its antioxidant, anti-oxidation of LDL-C, anti-tumor,
anti-inflammatory, inhibiting activation of endothelial
cells, anti-atherogenic, anti-thrombotic, cholesterol-
lowering, decreased immune response, protection of red
blood cells against H2O2, antiplatelet, anti-cancer and
cardiovascular protective properties of this compound
can be related to its powerful anti-free-radical properties
(45,46). Deiana et al, studied the LLC-PK1 cell line
from pig epithelial cells and found that glucuronide
metabolites obtained from hydroxytyrosol inhibit
oxidative damage and cell death (47). The inhibition is
performed through a significant inhibition of MDA, fatty
acid hydroperoxides, and 7-Ketocholestrol. In another
study conducted by Deiana et al (47), the effect of
hydroxytyrosol and its metabolite, homovanillic alcohol
was investigated on renal epithelial LLC-PK1 cells
damaged by H2O2. In this study, the protective effect of
homovanillic alcohol and hydroxytyrosol in a dose of 10
µmole was evaluated on lipid peroxidation induced by
H2O2. In fact, a 10 µmole dose of homovanillic alcohol
and hydroxytyrosol reduced the MDA and increased
unsaturated fatty acids and cholesterol (47). In total,
the protective effect of hydroxytyrosol was reported
more than the metabolites of homovanillic alcohol.
Other studies, including a study conducted by Loru
and colleagues on LLC-PK1 kidney cells, revealed that
doses of 1, 5 and 10 µM of hydroxytyrosol, especially
a dose of 10 µM, decreases the MDA level in treated
group compared with control group (48). Therefore,
hydroxytyrosol, with its antioxidant properties, inhibits
the production of fatty acids, hydroperoxides and
7-Ketocholesterol. In another study on the protective
effects of hydroxytyrosol in nephrotoxicity induced by
cyclosporine, it was proven that this phenolic compound
eliminates superoxide produced by cyclosporine (49).
Additionally, hydroxytyrosol increases GSH, but has
no protective effect on the GFR, the aorta, renal artery
systolic and diastolic pressures (49). Other studies, such
as the study conducted by Capasso and colleagues on
immortal rat kidney cells, showed that hydroxytyrosol
inhibits peroxidation of the membrane lipid and
generates reactive oxygen species, resulting in a protective
effect against renal toxicity (49). Hamden and colleagues
demonstrated that hydroxytyrosol increased the activity
of antioxidant enzymes such as CAT, SOD, and GSH
peroxidase, and reduced lipid peroxidation and urea and
serum creatinine levels in the kidneys (50). The study
conducted by Mahmoudi et al, on the protective effect
of hydroxytyrosol on the kidneys of lactating rats affected
by Bisphenol A and their offspring, revealed that, in both
mothers and offspring groups treated with this phenolic
compound, serum creatinine returned to normal and
MDA levels decreased significantly (38). An increase in
the amount of CAT and total antioxidant capacity was
observed in the groups treated with hydroxytyrosol.
Histologically, glomerular necrosis and, in particular,
tubular necrosis of the near and far twisted tubules
decreased in the groups treated with hydroxytyrosol (48).
4.5. Tyrosol
The olive tree – and, more specifically, pure olive oil –
can be considered as one of the main sources of tyrosol
(4- (2-hydroxy ethyl phenol)) as a phenol compound
(51). Several properties have been introduced for tyrosol,
including antioxidants, especially against the oxidant
compounds such as peroxynitrite and superoxide anti-
neoplastic, anti-osteoporosis, inhibiting the oxidation
of LDL-C, anti-stress properties, anti-depressants,
anti-inflammatory, protective cardiovascular system
and nervous system protection (51,52). In the study
conducted by Chandramohan et al, the administration
of tyrosol in rats with diabetes increased the activity of
hexokinase and glucose-6-phosphate dehydrogenase
enzyme in the animals’ kidneys (53). On the other hand,
the recovery of activity of carboxymethyl pyruvate kinase,
fructose 1, 6-bisphosphatase, and glucose 6-phosphatase
was observed in the kidneys of diabetic rats using this
antioxidant. In addition to the mentioned effects, tyrosol
led to the recovery of activities of enzymatic and non-
enzymatic antioxidants (vitamins E and C) in all mice
treated with this compound (53).
5. Conclusions
According to the previous studies, acute and chronic
kidney diseases are among those factors that can lead
to renal failure and, hence, impose real costs to the
economy. On the one hand, due to the complexity
of the pathogenesis of the disease, it is possible that
different systems are mostly involved in the pathogenesis
of kidney disease, especially oxidative stress and the
production of free radicals such as reactive oxygen
species. Therefore, according to the mechanism of
pathogenicity, appropriate therapeutic strategies for the
treatment of these diseases often involves the elimination
of the antioxidant compounds through antioxidant
treatment and by strengthening the internal antioxidant
system, and weighing the scales toward the antioxidant
compounds against the oxidant compounds. In order
to provide antioxidant sources for the treatment of
kidney diseases, many chemical drugs are currently
used. However, due to their various side effects, the
Babaeenezhad et al
Journal of Nephropathology, Vol 8, No 1, January 2019
use of antioxidant compounds derived from plants
have been recommended in various and related studies
as rich resources. However, various active ingredients
(oleuropein, hydroxytyrosol and oleic acid) are derived
from different parts of the olive plant, such as leaves,
fruits, and their products. Olive oil that can be used as
a protective compound for coping with kidney disease
(renal toxicity, renal ischemia-reperfusion, kidney
stones, kidney damage caused by lupus erythematosus
and urinary tract infections) and reduce kidney damage
parameters (urea, creatinine and MDA), as mentioned
above. Hence, it is suggested that, due to the numerous
health benefits of the olive tree that have been listed
and its active components, and the scant studies on the
effects of herbal treatments for diseases, especially renal
damage, further studies should be conducted in this field
in order to discover further pharmaceutical products
from this plant.
Authors’ contribution
Primary draft; HA and RMK. Editing the final
manuscript: HA. All authors read and sign the final
Conflicts of interest
The authors declared no competing interests.
Ethical considerations
Ethical issues (including plagiarism, data fabrication,
double publication) have been completely observed by
the authors.
1. Stępniewska J, Gołembiewska E, Dołęgowska B, Domański
M, Ciechanowski K. Oxidative stress and antioxidative
enzyme activities in chronic kidney disease and different
types of renal replacement therapy. Curr Protein Pept Sci.
2015;16(3):243-8. doi: 10.2174/13892037166661502241
2. Waterman E, Lockwood B. Active components and clinical
applications of olive oil. Altern Med Rev. 2007;12(4):331-
3. Teymouri M, Badiee A, Golmohammadzadeh S,
Sadri K, Akhtari J, Mellat M, et al. Tat peptide and
hexadecylphosphocholine introduction into pegylated
liposomal doxorubicin: An in vitro and in vivo study on
drug cellular delivery, release, biodistribution and antitumor
activity. Int J Pharm. 2016;511(1):236-44. doi: 10.1016/j.
4. Mokni M, Hamlaoui S, Kadri S, Limam F, Amri M,
Marzouki L, et al. Grape seed and skin extract protects
kidney from doxorubicin-induced oxidative injury. Pak J
Pharm Sci. 2016; 29(3):961-8.
5. Al-Abbasi FA, Alghamdi EA, Baghdadi MA, Alamoudi
AJ, El-Halawany AM, El-Bassossy HM, et al. Gingerol
synergizes the cytotoxic effects of doxorubicin against liver
cancer cells and protects from its vascular toxicity. Molecules.
2016;21(7):E886. doi: 10.3390/molecules21070886.
6. Ansley DM, Wang B. Oxidative stress and myocardial injury
in the diabetic heart. J Pathol. 2013;229(2):232-41. doi:
7. Kumral A, Giriş M, Soluk-Tekkeşin M, Olgaç V, Doğru-
Abbasoğlu S, Türkoğlu Ü, et al. Effect of olive leaf extract
treatment on doxorubicin-induced cardiac, hepatic and renal
toxicity in rats. Pathophysiology. 2015;22(2):117-23. doi:
8. Ahmadvand H, Bagheri S, Tamjidi-Poor A, Cheraghi M,
Azadpour M, Ezatpour B, et al. Biochemical effects of
oleuropein in gentamicin-induced nephrotoxicity in rats.
ARYA Atheroscler. 2016;12(2):87-93.
9. Tavafi M, Ahmadvand H, Tamjidipour A, Rasolian B.
Effect of normobaric hyperoxia on gentamicin-induced
nephrotoxicity in rats. Iran J Basic Med Sci. 2014;17(4):287-
10. Ahmadvand H, Ghasemi Dehnoo M, Dehghani A, Bagheri
S, Cheraghi RA. Serum paraoxonase 1 status and its
association with atherogenic indexes in gentamicin-induced
nephrotoxicity in rats treated with coenzyme Q10. Ren Fail.
2014;36(3):413-8. doi: 10.3109/0886022X.2013.865154.
11. Tavafi M, Ahmadvand H. Effect of rosmarinic acid
on inhibition of gentamicin induced nephrotoxicity
in rats. Tissue Cell. 2011;43(6):392-7. doi: 10.1016/j.
12. Tavafi M, Ahmadvand H, Toolabi P. Inhibitory effect of olive
leaf extract on gentamicin-induced nephrotoxicity in rats.
Iran J Kidney Dis. 2012;6(1):25-32.
13. Rasoulian B, Kaeidi A, Pourkhodadad S, Dezfoulian O,
Rezaei M, Wahhabaghai H, et al. Effects of pretreatment
with single-dose or intermittent oxygen on Cisplatin-induced
nephrotoxicity in rats. Nephrourol Mon. 2014;6(5):e19680.
doi: 10.5812/numonthly.19680.
14. Mostafa-Hedeab G, Sati LM, Elnaggar HM, Elgatlawey ZO,
Eltwab AA, Elsaghayer WA, et al. Ameliorating effect of olive
leaf extract on cyclosporine-induced nephrotoxicity in rats.
Iran J Kidney Dis. 2015;9(5):361-8.
15. Sacerdoti D, Borsato M, Rigotti P, Amodio P, Angeli
P, Ferraresso M, Plebani M, Gatta A. Increased renal
production of cytochrome P450-dependent metabolites of
arachidonic acid in cyclosporine-induced nephrotoxicity. Adv
Prostaglandin Thromboxane Leukot Res. 1991;21B:689-92.
16. Nakbi A, Tayeb W, Dabbou S, Chargui I, Issaoui M, Zakhama
A, et al. Hypolipidimic and antioxidant activities of virgin
olive oil and its fractions in 2,4-diclorophenoxyacetic acid-
treated rats. Nutrition. 2012;28(1):81-91. doi: 10.1016/j.
17. Nakbi A, Tayeb W, Dabbou S, Issaoui M, Grissa AK, Attia N,
Hammami M. Dietary olive oil effect on antioxidant status
and fatty acid profile in the erythrocyte of 2,4-D- exposed Journal of Nephropathology, Vol 8, No 1, January 2019
Protective effects of olive in renal failures
rats. Lipids Health Dis. 2010;9:89. doi: 10.1186/1476-
18. Sugiyama T, Nagata J, Yamagishi A, Endoh K, Saito M,
Yamada K, et al. Selective protection of curcumin against
carbon tetrachloride-induced inactivation of hepatic
cytochrome P450 isozymes in rats. Life Sci. 2006;78(19):
2188-93. doi: 10.1016/j.lfs.2005.09.025.
19. Aragno M, Tamagno E, Poli G, Boccuzzi G, Brignardello
E, Danni O. Prevention of carbon tetrachloride-
induced lipid peroxidation in liver microsomes from
dehydroepiandrosterone-pretreated rats. Free Radic Res.
1994;21(6):427-35. doi: 10.3109/10715769409056595.
20. Es Haghi M, Dehghan G, Banihabib N, Zare S, Mikaili
P, Panahi F. Protective effects of Cornus mas fruit extract
on carbon tetrachloride induced nephrotoxicity in rats.
Indian J Nephrol. 2014;24(5):291-6. doi: 10.4103/0971-
21. Cho SY, Choi SM, Park SH, Lee DG, Choi JH, Yoo JH.
Amikacin therapy for urinary tract infections caused by
extended-spectrum β-lactamase-producing Escherichia coli.
Korean J Intern Med. 2016;31(1):156-61. doi: 10.3904/
22. Bulut G, Basbugan Y, Ari E, Erten R, Bektas H,
Alp HH, et al. Paricalcitol may improve oxidative
DNA damage on experimental amikacin-induced
nephrotoxicity model. Ren Fail. 2016; 38(5): 751-8. doi:
23. Abdel-Gayoum AA, Al-Hassan AA, Ginawi IA, Alshankyty
IA. The ameliorative effects of virgin olive oil and olive
leaf extract on amikacin-induced nephrotoxicity in the
rat. Toxicol Reports. 2015; 2: 1327–33. doi: 10.1016/j.
24. Ghosh S, Sarkar A, Bhattacharyya S, Sil PC. Silymarin
protects mouse liver and kidney from thioacetamide induced
toxicity by scavenging reactive oxygen species and activating
PI3K-Akt pathway. Front Pharmacol. 2016;7:481. doi:
25. Latha SM, Pai MR, Pai PK. Thioacetamide toxicity and the
lung: histological analysis. Indian J Physiol Pharmacol. 2003;
26. Cole P, Rodu B. Epidemiologic studies of chrome and cancer
mortality: a series of meta-analyses. Regul Toxicol Pharmacol.
27. Saber TM, M. R. Farag, MR, Cooper RG. Ameliorative
effect of extra virgin olive oil on hexavalent chromium-
induced nephrotoxicity and genotoxicity in rats. Revue Méd
Vét. 2015;166(1-2):11-9.
28. Boroushaki MT, Mollazadeh H, Rajabian A, Dolati
K, Hoseini A, Paseban M, et al. Protective effect of
pomegranate seed oil against mercuric chloride induced
nephrotoxicity in rat. Ren Fail. 2014;36(10): 1581-6. doi:
29. Necib Y, Bahi A, Zerizer S, Abdennour C, Boulakoud SM.
Effect of virgin olive oil (Olea europea L.) on kidney function
impairment and oxidative stress induced by mercuric chloride
in rats. Am J Biochem Biotechnol. 2013;9(4): 415-22
30. Rafighdoost H, Tavafi M, Jafari pour L, Rasoulian B,
Ahmadvand H, et al. Effect of olive leaf extract in inhibition
of renal ischemia-reperfusion injuries in rat Anat Sci J. 2013;
10(3): 161-5.
31. Monti E, Trinchieri A, Magri V, Cleves A, Perletti G. Herbal
medicines for urinary stone treatment. A systematic review.
Arch Ital Urol Androl. 2016;88(1):38-46. doi: 10.4081/
aiua.2016.1.38. Review.
32. Roozbeh J, Eshraghian A, Raeesjalali G, Behzadi S,
Nikeghbalian S, Sagheb MM, et al. Outcomes of kidney
transplantation in patients with systemic lupus erythematosus:
a single-center study. Iran J Kidney Dis. 2011;5(1):53-6.
33. Aparicio-Soto M, Sánchez-Hidalgo M, Cárdeno A, Rosillo
MÁ, Sánchez-Fidalgo S, Utrilla J, et al. Dietary extra virgin
olive oil attenuates kidney injury in pristane-induced
SLE model via activation of HO-1/Nrf-2 antioxidant
pathway and suppression of JAK/STAT, NF-κB and MAPK
activation. J Nutr Biochem. 2016;27:278-88. doi: 10.1016/j.
34. Pourkhodadad S, Alirezaei M, Moghaddasi M, Ahmadvand
H, Karami M, Delfan B, et al. Neuroprotective effects
of oleuropein against cognitive dysfunction induced by
colchicine in hippocampal CA1 area in rats. J Physiol Sci.
2016; 66(5): 397-405. doi: 10.1007/s12576-016-0437-4.
35. Li X, Liu Y, Jia Q, LaMacchia V, O’Donoghue K, Huang Z.
A systems biology approach to investigate the antimicrobial
activity of oleuropein. J Ind Microbiol Biotechnol. 2016;
43(12): 1705-17. doi:10.1007/s10295-016-1841-8.
36. Khalatbary AR, Ahmadvand H. Effect of oleuropein on
tissue myeloperoxidase activity in experimental spinal cord
trauma. Iran Biomed J. 2011;15(4):164-7. doi: 10.6091/
37. Khalatbary AR, Ahmadvand H. Neuroprotective effect of
oleuropein following spinal cord injury in rats. Neurol Res.
2012;34(1):44-51. doi: 10.1179/1743132811Y.0000000058
38. Mahmoudi A, Ghorbel H, Bouallegui Z, Marrekchi R, Isoda
H, Sayadi S. Oleuropein and hydroxytyrosol protect from
bisphenol A effects in livers and kidneys of lactating mother
rats and their pups’. Exp Toxicol Pathol. 2015;67(7-8):413-
25. doi: 10.1016/j.etp.2015.04.007.
39. Ahmadvand H, Ghasemi Dehnoo M, Cheraghi R, Rasoulian
B, Ezatpour B, et al Amelioration of altered serum, liver, and
kidney antioxidant enzymes activities by sodium selenite in
alloxan-induced diabetic rats Rep Biochem Mol Biol. 2014;
40. Potočnjak I, Škoda M, Pernjak-Pugel E, Peršić MP, Domitrović
R. Oral administration of oleuropein attenuates cisplatin-
induced acute renal injury in mice through inhibition of
ERK signaling. Mol Nutr Food Res. 2016;60(3):530-41. doi:
41. Alirezaei M, Dezfoulian O, Kheradmand A. Novel
Antioxidant Properties of Ghrelin and Oleuropein Versus
Lipopolysaccharide-Mediated Renal Failure in Rats. Int J
Pept Res Ther. 2015;21(4):411–2. doi: 10.1007/s10989-
42. Sales-Campos H, Souza PR, Peghini BC, da Silva JS, Cardoso
CR An overview of the modulatory effects of oleic acid in
health and disease. Mini Rev Med Chem. 2013;13(2):201-
Babaeenezhad et al
Journal of Nephropathology, Vol 8, No 1, January 2019
Copyright © 2019 The Author(s); Published by Society of Diabetic Nephropathy Prevention. This is an open-access article distributed
under the terms of the Creative Commons Attribution License (, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is properly cited.
10. doi: 10.2174/1389557511313020003.
43. Liu H, Jia Z, Soodvilai S, Guan G, Wang MH, Dong Z, et
al. Nitro-oleic acid protects the mouse kidney from ischemia
and reperfusion injury. Am J Physiol Renal Physiol. 2008;
295(4):F942-9. doi: 10.1152/ajprenal.90236.2008.
44. Jenkin HM, Anderson LE. The effect of oleic acid on the
growth of monkey kidney cells (LLC-MK2). Exp Cell Res.
1970;59(1):6-10. Doi: 10.1016/0014-4827(70)90616-6.
45. Bulotta S, Celano M, Lepore SM, Montalcini T, Pujia A, Russo
D. Beneficial effects of the olive oil phenolic components
oleuropein and hydroxytyrosol: focus on protection against
cardiovascular and metabolic diseases. J Transl Med. 2014;
12:219. doi: 10.1186/s12967-014-0219-9.
46. Vilaplana-rez C, Auñón D, García-Flores LA, Gil-Izquierdo
A. Hydroxytyrosol and potential uses in cardiovascular
diseases, cancer, and AIDS. Front Nutr. 2014;1:18. doi:
47. Deiana M, Incani A, Rosa A, Atzeri A, Loru D, Cabboi B,
et al. Hydroxytyrosol glucuronides protect renal tubular
epithelial cells against H(2)O(2) induced oxidative damage.
Chem Biol Interact. 2011;193(3):232-9. doi: 10.1016/j.
48. Loru D, Incani A, Deiana M, Corona G, Atzeri A, Melis MP,
et al. Protective effect of hydroxytyrosol and tyrosol against
oxidative stress in kidney cells. Toxicol Ind Health. 2009;
25(4-5):301-10. doi: 10.1177/0748233709103028.
49. Capasso G, Di Gennaro CI, Della Ragione F, Manna C, Ciarcia
R, Florio S, et al. In vivo effect of the natural antioxidant
hydroxytyrosol on cyclosporine nephrotoxicity in
rats. Nephrol Dial Transplant. 2008;23(4):1186-95.
doi: 10.1093/ndt/gfm784.
50. Hamden K, Allouche N, Damak M, Elfeki A.
Hypoglycemic and antioxidant effects of phenolic
extracts and purified hydroxytyrosol from olive mill
waste in vitro and in rats. Chem Biol Interact. 2009;
180(3):421-32. doi: 10.1016/j.cbi.2009.04.002.
51. Sato K, Mihara Y, Kanai K, Yamashita Y, Kimura Y,
Itoh N. Relative potency of tyrosol in the treatment
of endotoxin-induced uveitis in rats. J Ve t Med Sci.
2016; 78(10):1631-4. doi: 10.1292/jvms.16-0254.
52. Covas MI, Mi-Casas E, Fitó M, Farré-Albadalejo
M, Gimeno E, Marrugat J, et al. Bioavailability of
tyrosol, an antioxidant phenolic compound present
in wine and olive oil, in humans. Drugs Exp Clin
Res. 2003;29(5-6):203-6.
53. Chandramohan R, Pari L, Rathinam A, Sheikh
BA. Tyrosol, a phenolic compound, ameliorates
hyperglycemia by regulating key enzymes of
carbohydrate metabolism in streptozotocin induced
diabetic rats. Chem Biol Interact. 2015;229:44-54.
doi: 10.1016/j.cbi.2015.01.026.
... Although standard treatment for testicular TD injury is surgery, some interventions have recently been suggested to reduce injury; including ROS scavenging agents, anti-inflammatory agents, natural products, and synthetic drugs [4]. Antioxidants are able to protect cells and tissues against various diseases particularly disorders caused by ROS [12][13][14][15][16]. Therefore, prescribing antioxidants to reduce oxidative stress seems important and necessary [17][18][19][20][21][22]. The researchers have been described the antioxidant role of vasopressin previously [23]. ...
... The increment of consumption of plant derived natural antioxidants can be a compensatory way to reduce the harmful effects of ROS [18][19][20]. Ziziphus nummularia or Ramilak is an important plant in the Rhamnaceae family. The growing location of Z. nummularia is in South and West Asia and some African countries including Zimbabwe, Mauritania, Nigeria and Uganda. ...
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Background/Aims: The number of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is increasing. In an outpatient setting, there are limited therapeutic options to treat ESBL-producing pathogens. We evaluated the outcomes of amikacin outpatient parenteral antibiotic therapy (OPAT) for UTIs caused by ESBL-EC in patients not pre-treated with carbapenem. Methods: We retrospectively evaluated the outcomes of amikacin OPAT for UTIs caused by ESBL-EC. Results: From November 2011 to October 2012, eight females, who could not be hospitalized for carbapenem treatment, were treated with amikacin OPAT for nine episodes of non-bacteremic ESBL-EC UTIs. Seven of the eight patients had one or more comorbidities. Of the nine UTI cases, three had symptomatic lower UTIs and six had non-bacteremic upper UTIs. In all of the cases, symptomatic and laboratory improvements were observed following amikacin OPAT. One patient showed a delayed relapse with bilateral microabscesses 3 weeks after treatment cessation; however, a clinical and microbiological cure was eventually reached. All of the patients were able to tolerate amikacin OPAT without any significant nephrotoxicity or ototoxicity. Conclusions: Amikacin OPAT represents a feasible therapeutic option for non-bacteremic UTIs caused by ESBL-EC in settings with limited resources.
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Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl₄-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4'-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC50 values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG₂ and Huh7, cells decreasing its IC50s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G₂/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G₂/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM) was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics.
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Tyrosol (Tyr) is a natural phenolic antioxidant with diverse biological activities. We compared the anti-inflammatory effects of intravenously administered Tyr versus prednisolone (PSL) in an endotoxin-induced uveitis (EIU) rat model. Intravenous administration of 100 mg/kg Tyr was performed 2 hr before, simultaneously and 2 hr after lipopolysaccharide (LPS) injection. Tyr treatment was associated with decreased inflammatory cell number, protein concentration, tumor necrosis factor (TNF)-α, PGE2 and NO levels in AqH and improvements in histopathologic evidence of EIU in ocular tissue at 24 hr after LPS injection. 100 mg/kg Tyr and 1 mg/kg PSL (administered on the same schedule as Tyr) had comparable anti-inflammatory effects. Taken together, Tyr may represent a promising therapeutic agent for the management of intraocular inflammatory diseases.
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The study investigated the protective effect of grape seed and skin extract (GSSE) against doxorubicin-induced renal toxicity in healthy rats. Animals were treated with GSSE or not (control), for 8 days, administered with doxorubicin (20mg/kg) in the 4th day, and renal function as well as oxidative stress parameters were evaluated. Data showed that doxorubicin induced renal toxicity by affecting renal architecture and plasma creatinine. Doxorubicin also induced an oxidative stress characterized by an increase in malondialdehyde (MDA), calcium and H2O2 and a decrease in catalase (CAT) and superoxide dismutase (SOD). Unexpectedly doxorubicin increased peroxidase (POD) and decreased carbonyl protein and plasma urea. Treatment with GSSE counteracted almost all adverse effects induced by doxorubicin. Data suggest that doxorubicin induced an oxidative stress into rat kidney and GSSE exerted antioxidant properties, which seem to be mediated by the modulation of intracellular calcium.
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Background: Oleuropein is a natural antioxidant and scavenging free radicals. In the present study, we examined effect of oleuropein on the paraoxonase 1 (PON1) activity, lipid peroxidation, lipid profile, atherogenic indexes, and relationship of PON1 activity by high-density lipoprotein-cholesterol (HDL-C) and atherogenic indices in gentamicin (GM)-induced nephrotoxicity in rats. Methods: This is a lab trial study in Khorramabad, Lorestan province of Iran (2013). 30 Sprague-Dawley rats were divided into three groups to receive saline; GM, 100 mg/kg/day; and GM plus oleuropein by 15 mg/kg intraperitoneal daily, respectively. After 12 days, animals were anesthetized, blood samples were also collected before killing to measure the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and very LDL (VLDL), HDL-C, atherogenic index, lipid peroxidation, and the activities of PON1 of all groups were analyzed. Data were analyzed, and P < 0.050 was considered significant. Results: Oleuropein significantly decreased lipid peroxidation, TG, TC, LDL, VLDL, atherogenic index, atherogenic coefficient (AC), and cardiac risk ratio (CRR). HDL-C level was significantly increased when treated with oleuropein. The activity of PON1 in treated animals was (62.64 ± 8.68) that it was significantly higher than untreated animals (47.06 ± 4.10) (P = 0.047). The activity of PON1 in the untreated nephrotoxic rats was significantly lower than that of control animals (77.84 ± 9.43) (P = 0.030). Furthermore, the activity of PON1 correlated positively with HDL-C and negatively with AC, CRR 1, and CRR 2 in the treated group with oleuropein. Conclusion: This study showed that oleuropein improves PON1 activity, lipid profile, and atherogenic index and can probably decrease the risk of cardiovascular death in nephrotoxic patients.
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Objective: To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract. Methods: To be eligible, full-length articles should include the results of randomized controlled trials enrolling patients affected by urolithiasis, reporting any comparison between an experimental herbal agent versus placebo or any active comparator, aimed at preventing the formation or facilitating the dissolution of calculi in any portion of the urinary tract. Fifteen databases were searched for relevant references. The primary outcomes investigated were (i) the reduction of stone size and/or number and (ii) the urinary excretion rates of calcium, urate, or oxalate. The secondary outcome of the review was the adverse effects (AE) of treatment. Risk of bias (ROB) and quality of the evidence were assessed according to Cochrane and GRADE guidelines. We performed a random-effect meta-analysis. Results: 541 articles were retrieved and 16 studies were finally confirmed as eligible. Multiple Cochrane ROB tool items were rated as having high risk of bias in each analyzed trial report. Pooled analysis of continuous data could be performed for three different comparisons: (i) phytotherapy versus citrate as single agent (ii) phytotherapy versus placebo, (iii) preparation of Didymocarpus pedicellata (DP)--combined with other herbal agents--versus placebo. Results showed that citrate is superior to phytotherapy in significantly decreasing both the size of urinary stones (mean difference: phytotherapy, 0.42 mm higher; 95% CI: 0.23 to 0.6; Z = 4.42, P < 0.0001; I2 = 30%) and the urinary excretion rate of urate (mean difference: 42.32 mg/24h higher, 95% CI: 19.44 to 65.19; Z = 3.63, P = 0.0003; I2 = 96%), assessed after 3 months on-therapy. No significant differences in the excretion rates of urinary calcium or oxalate were found. The DP preparation was superior to placebo in inducing total clearance (risk ratio: 6.19, 95% CI: 2.60 to 14.74; Z = 4.12, P < 0.0001; I2 = 0%) and size reduction (mean difference: DP preparation, 4.93 mm lower; 95% CI: -9.18 to -0.67; Z = 2.27, P = 0.02; I2 = 99%) of renal and ureteral stones after 3 months of therapy. No significant differences in the inter-arm variation of excretion rates of urinary calcium or urate were found as result of the pooled phytotherapy-placebo comparison. Herbal remedies were in general devoid of side effects and in few cases citrate appeared to induce GI disturbances in a higher fraction of patients. Most reports did not provide inferential data concerning AE, and meta-analysis was not feasible. Conclusions: Citrate is more effective than phytotherapy in decreasing the size of existing calculi in the urinary tract and in decreasing the urinary excretion rate of uric acid. A preparation containing Didymocarpus pedicellata combined with other herbal agents induces stone size reduction and clearance significantly better than placebo. Mayor limitations in the applicability of these results are the low quality of the evidence and the multiple sources of bias assessed in the studies included in the present review.
Silymarin (SMN) has been shown to possess a wide range of biological and pharmacological effects. Besides, SMN has antioxidant and free radical scavenging activities. Thioacetamide (TAA) is a well-documented liver toxin that requires oxidative bioactivation to elicit its hepatotoxic effect which ultimately modifies amine-lipids and proteins. Our study has been designed in a TAA exposed mouse model to investigate whether SMN could protect TAA-induced oxidative stress mediated hepatic and renal damage. Results suggest that TAA generated reactive oxygen species (ROS), caused oxidative stress and induced apoptosis in the liver and kidney cells via JNK as well as PKC and MAPKs signaling. All these detrimental effects of TAA could, however, be suppressed by SMN which not only scavenged ROS but also induced PI3K-Akt cell survival pathway in the liver and prevented apoptotic pathways in both the organs. Histological studies, collagen staining and DNA fragmentation analysis also supported our results. Combining, we say that SMN possess beneficial role against TAA mediated hepatic and renal pathophysiology.
Oleuropein and its hydrolysis products are olive phenolic compounds that have antimicrobial effects on a variety of pathogens, with the potential to be utilized in food and pharmaceutical products. While the existing research is mainly focused on individual genes or enzymes that are regulated by oleuropein for antimicrobial activities, little work has been done to integrate intracellular genes, enzymes and metabolic reactions for a systematic investigation of antimicrobial mechanism of oleuropein. In this study, the first genome-scale modeling method was developed to predict the system-level changes of intracellular metabolism triggered by oleuropein in Staphylococcus aureus, a common food-borne pathogen. To simulate the antimicrobial effect, an existing S. aureus genome-scale metabolic model was extended by adding the missing nitric oxide reactions, and exchange rates of potassium, phosphate and glutamate were adjusted in the model as suggested by previous research to mimic the stress imposed by oleuropein on S. aureus. The developed modeling approach was able to match S. aureus growth rates with experimental data for five oleuropein concentrations. The reactions with large flux change were identified and the enzymes of fifteen of these reactions were validated by existing research for their important roles in oleuropein metabolism. When compared with experimental data, the up/down gene regulations of 80% of these enzymes were correctly predicted by our modeling approach. This study indicates that the genome-scale modeling approach provides a promising avenue for revealing the intracellular metabolism of oleuropein antimicrobial properties.
Mercuric chloride (HgCl2) is an environmental and industrial toxicant that affects many tissues. Considering oxidative stress is an important component of mercury induced hepatotoxicity, antioxidants are expected to play a protective role against it. The present study was designed to investigate the probable effects of pomegranate seed oil (PSO) on hepatotoxicity induced by HgCl2 administration in rats. Rats were divided into five groups. Group 1 and 2 received corn oil (1 mL/kg, i.p.) and PSO (0.8 mL/kg, i.p.), respectively. Group 3 was treated with HgCl2 (5 mg/kg, i.p.) for 3 days. In groups 4 and 5 PSO (0.4 and 0.8 mL/kg i.p., respectively) was given 1 h before HgCl2 administration. Twenty four hours after last injection of HgCl2, blood samples and specimens of liver were taken. HgCl2 administration led to significant increase in liver malondialdehyde level, significant reduction in total sulfhydryl content and significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase activity (AST), compared to control group. The histopathological changes such as necrosis, inflammatory cell infiltration and hepatocellular vacuolization were observed. PSO administration (0.8 mL/kg i.p.) improved the liver function in HgCl2 intoxicated animals as indicated by the significant decline in increased levels of AST, ALT in serum, MDA level and significant elevation in decreased total sulfhydryl content. Histological studies revealed milder hepatic lesions in PSO treated samples. The results indicated that oxidative stress may be an important mechanism of HgCl2 induced hepatic injury and dysfunction and PSO may be a useful agent for the prevention of HgCl2 induced oxidative damage in rat liver.