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Evaluation of toxicological implications of inhalation exposure to kerosene fumes and petrol fumes in rats



Toxicological implications of exposure to ungraded concentrations of kerosene and petrol fumes in albino Wistar rats were investigated after two weeks of 4 hours daily inhalation. Serum aminotransferases (AST and ALT), alkaline phosphatase (ALP), total choles-terol (Chol), triglyceride (TG) levels and histological analysis of the liver tissues were used as diagnostic markers to assess liver dysfunction. The mean levels of these markers determined for the group of rats exposed to kerosene and petrol fumes (test groups), as compared with the levels for the control group were significantly (p < 0.05) higher. ALT, AST and ALP levels of the kerosene exposed group were raised by 191%, 161% and 204% while serum total cholesterol and TG levels increased by 129% and 118%, respectively. The increases in the serum levels of AST, ALT, ALP, Chol, TG in the petrol exposed group were 177%, 140%, 191%, 100% and 97%, respectively, when compared with the controls. Histological analysis of the liver tissues of the experimental test groups indicated degenerative changes in the ultrastructural integrity of the hepatic cells. These results showed that frequent exposure to kerosene and petrol fumes may be highly deleterious to the liver cells.
Volume 49(3-4):19-22, 2005
Acta Biologica Szegediensis
Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Nigeria
Evaluation of toxicological implications of inhalation
exposure to kerosene fumes and petrol fumes in rats
Friday E Uboh, Monday I Akpanabiatu*, Eyong U Eyong, Patrick E Ebong, Offiong O Eka
Toxicological implications of exposure to ungraded concentrations of kerosene
and petrol fumes in albino Wistar rats were investigated after two weeks of 4 hours daily
inhalation. Serum aminotransferases (AST and ALT), alkaline phosphatase (ALP), total choles
terol (Chol), triglyceride (TG) levels and histological analysis of the liver tissues were used as
diagnostic markers to assess liver dysfunction. The mean levels of these markers determined for
the group of rats exposed to kerosene and petrol fumes (test groups), as compared with the
levels for the control group were significantly (p < 0.05) higher. ALT, AST and ALP levels of the
kerosene exposed group were raised by 191%, 161% and 204% while serum total cholesterol
and TG levels increased by 129% and 118%, respectively. The increases in the serum levels of
AST, ALT, ALP, Chol, TG in the petrol exposed group were 177%, 140%, 191%, 100% and 97%,
respectively, when compared with the controls. Histological analysis of the liver tissues of the
experimental test groups indicated degenerative changes in the ultrastructural integrity of the
hepatic cells. These results showed that frequent exposure to kerosene and petrol fumes may
be highly deleterious to the liver cells.
Acta Biol Szeged 49(3-4):19-22 (2005)
liver enzymes
serum lipids
Accepted April 15, 2005
*Corresponding author. E-mail:
Kerosene and petrol are distilled from crude petroleum and
vapours obtained from their evaporation may be considered
as kerosene and petrol fumes. These fractions of crude pe
troleum contain aliphatic, aromatic and a variety of other
branched saturated and unsaturated hydrocarbons (Henderson
et al. 1993; Kato et al. 1993; Anderson et al. 1995). It has
been demonstrated that after inhalation of equal concentra-
tions of petroleum vapour through chronic exposure, lower
concentrations of saturated hydrocarbons are detected in hu-
man and animal blood than that of the unsaturated aromatic
hydrocarbons (Zahlsen et al. 1993). Biological monitoring
of exposure to bitumen fumes during road-paving operations
indicated urinary excretion of 1-hydroxypyrene and thioethers
in the exposed workers (Burgaz et al. 1992).
Petroleum fumes are ubiquitous in our environment and
the common sources of contact or exposure are petrochemical
industries (refineries, oils fields, filling stations) and homes.
The applications of kerosene as cooking and lighting fuels in
the home have resulted in direct exposure of these products to
a good percentage of the populace. Moreover, the day-to-day
use of petrol outside the industrial settings is likely to have
the same effect on the users as kerosene since they have been
reported to contain most of the same hydrocarbons. However,
the most affected are those who occupationally exposed to
the fumes (Smith et al. 1993; Carballo et al. 1994; Rothman
et al. 1996).
Despite the high utilization of kerosene and petrol, our
knowlegde is sparse on the toxicological effects of inhaling
the composite fumes evaporating from kerosene and petrol.
However, mutagenic, genotoxic, carcinogenic, neurotoxic,
immunotoxic and haemotoxic effects of some petroleum and
petrochemical products’ constituents have been reported in
experimental studies on humans and animals (Sim 1980; Hu
and Wells 1994; Hallier et al. 1995). Hydrocarbons and other
constituents of petroleum and petrochemical products, like
other xenobiotics, are metabolized in the liver to a greater
extent (Sims 1980; Nelson et al. 1993). Ueng et al. (1998)
reported that exposure of rats to motorcycle exhaust and or-
ganic extracts of the exhaust particulate caused a dose- and
time-dependent increase in cytochrome P-450-dependent
monoxygenases and glutathione-S-transferase in the liver,
kidney and lung microsomes. Since kerosene and petrol con-
tain some of these constituents, chronic or frequent exposure
to their fumes may affect the normal liver functions.
The expression of toxicity of xenobiotics is usually de-
termined biochemically by the monitoring of some plasma
enzymes and lipids. A rise in AST, ALT, ALP, TG and choles-
terol are commonly measured as indices of the damage of the
liver cells (Abdel-Baset et al. 1997; Owu et al. 1998). In this
study we attempt to place on record the biotoxicity effects of
kerosene and petrol fumes on albino Wistar rats by measur-
ing some of these parameters. Histopathological changes in
the liver tissues of both the control and experimental animals
were also examined to support the biochemical findings.
Uboh et al.
Materials and Methods
Experimental animals
Young adult Wistar albino rats obtained from the animal
house of the College of Medical Science, University of Cala-
bar, Nigeria, were used for this study. Rats weighing 80-113
g were randomly selected into 3 groups (control, kerosene
and petrol, respectively) of eight animals each. Kerosene and
petrol were obtained from the Mobil Filling station, Calabar,
Nigeria. All experimental animals were housed in stainless
steel cages (60 cm x 30 x 45 cm) in a well-ventilated animal
house and had free access to water, and normal rat chow
obtained from Livestock Feeds, Calabar, Nigeria. The test
groups were exposed to kerosene and petrol fumes, respec-
tively, while the control group was kept in a section of the
experimental animal house free from petroleum fumes.
Exposure to kerosene and petrol fumes
The method of exposure employed in this study was by inha-
lation. The animal cages housing the test groups were placed
in exposure chambers measuring 150 cm x 90 cm x 210 cm.
Two highly perforated 1000 ml cans containing 500 ml of
kerosene were placed in the exposure chamber and the ani-
mals were allowed to inhale the fumes evaporating from the
cans. The same procedure was adopted for the petrol fumes.
In both cases, exposure lasted for 4 h daily for a period of 2
weeks. The time of exposure was 9.00 am to 1.00 pm, after
which the animals were transferred to fumes-free section of
the experimental animal house.
Collection of blood samples and liver tissues for
The animals were anesthetized with chloroform 24 h after the
last exposure and blood samples collected by cardiac puncture
into plain sample tubes. Serum samples were separated 1 h
after extraction of blood by centrifugation at 3000 g for 5
min and stored in a refrigerator. Biochemical analyses on the
serum samples were done 24 h after sample collection. The
liver tissues were collected and processed according to the
method reported by Akpanabiatu et al. (2003).
Biochemical analyses were carried out for the measure-
ment of serum alanine (ALT) and aspartate aminotransferases
(AST), alkaline phosphatase (ALP), cholesterol (Chol) and
triglyceride (TG) levels. Laboratory kit reagents (Randox
laboratory Ltd, UK) were used for all biochemical analyses
and the absorbances were read using a UV-Vis spectropho
tometer (DREL 3000 HACH). Statistical analysis was carried
out by employing Student’s t-test to compare the mean values
of the test groups with the controls (p < 0.05 was used as a
level of significance).
Results and Discussion
The serum enzymes activities of the controls and the animals
exposed to kerosene and petrol fumes are shown in Table 1.
The activity of ALT was significantly higher in animals ex-
posed to the kerosene and petrol fumes when compared to the
controls. The level of serum ALT activity has been reported to
be increased as a result of liver injury in patients developing
severe hepatotoxicity (Beckett et al. 1989). ALT might have
leaked from damaged cells, due to increased permeability of
the hepatocellular membrane, or due to necrosis, indicating
organ dysfunction (Mclntyre and Rosalki 1992).
The activity of AST was also significantly higher in
the animals exposed to kerosene and petrol fumes when
compared to the control animals. Increased activity of AST
has been reported in CCl
-intoxicated experimental animals
(Abdel-Baset et al. 1997). This increase may be due to the
abnormal dynamic properties of cellular membranes follow-
ing exposure to hydrocarbon fractions present in kerosene and
petrol fumes. Metabolism of aliphatic and aromatic hydro-
carbons which are the major constituents of petroleum fumes
as well as other xenobiotics have resulted in changes in the
cell membrane due to reactive free radical species (Leighton
et al. 1985; Bondy et al. 1995). The ratio of AST/ALT is
also an important index for the measurement of toxicity. The
decrease in the ratios in the animals exposed to kerosene
and petrol fumes showed that the liver is likely to be most
affected tissue.
Alkaline phosphatase activity in the animals exposed to
kerosene and petrol fumes were significantly higher (p < 0.05)
as compared to the control animals. This implies that dam-
ages may have occurred in the liver cells, since the activity of
this enzyme in the serum is reported to be increased in liver
damage (Abdel-Baset et al. 1997). Alkaline phosphatase is
involved in the transport of metabolites across the cell mem-
branes, protein synthesis, synthesis of certain enzymes, secre-
tory activities and glycogen metabolism. The increase in this
enzyme activity may not be unconnected with a disturbance
in the transport of metabolites or alteration in the synthesis of
certain enzymes as in other hepatotoxic conditions (Sharma
et al. 1995).
Group ALT (U/L) AST (UL) AST/ALT ALP (UL) Chol (mmol/l) TG (mmol/l)
Control 10.37±0.86 11.40±1.50 1.10 90.95±5.55 1.54±0.26 1.02±0.05
Kerosene fumes 30.12±0.58 29.72±1.37 0.99 276.24±3.36 3.53±0.33 2.22±0.05
Petrol fumes 28.70±1.06 27.33±3.06 0.95 264.67±0.36 3.08±0.36 2.01±0.09
Table 1. Effects of exposure to kerosene and petrol fumes on serum ALT, AST, ALP, Chol and TG levels of Wistar albino rats.
Inhalation exposure to kerosene and petrol fumes
The attendant effect of the exposure of experimental
animals to kerosene and petrol fumes is that the reactive in-
termediates generated may have disrupted the cell membranes
leading to enzyme leakage and tissue damage. Histological
analysis of the liver tissues of the experimental animals (Fig.
1) indicates that frequent exposure to kerosene and petrol
fumes affects the structural integrity of the liver cells. This
implies that the liver is one of the major target organs of
kerosene and petrol fumes-induced injury. The cumulative
oxidative damage is therefore likely to be one of the under
lying mechanisms responsible for the hepatotoxic effects of
kerosene and petrol fumes, as observed in this study.
The significant increase (p < 0.05) in the levels of serum
total cholesterol and triacylglycerol observed in this work
is an indication that inhalation exposure to kerosene and
petrol fumes also affect lipid metabolism. On one hand, lipid
metabolism is affected once there is liver damage since the
disturbance of cell membrane integrity is likely to cause some
membrane lipids to be released into circulation, while on the
other hand, it causes the tissue to compromise its effective-
ness in regulating lipid metabolism. There is a likelihood that
exposure to kerosene and petrol fumes predisposes the subject
to atherosclerotic condition.
In conclusion, the results of this work suggest that re-
peated exposure to kerosene and petrol fumes may elicit
hepatotoxicity, thereby impairing the normal liver function.
Petroleum workers therefore should have regular medical
check-up to ascertain their health condition. Further work
is ongoing on the influence of kerosene and petrol fumes on
oxidative metabolism.
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Figure 1. Photomicrograph of a typical liver section. (A) Control animal
showing normal liver cell architecture. (B) Kerosene fumes-exposed
animals show massive tissue degeneration. (C) Petrol fumes-exposed
animals show liver necrosis. Magnification: 50x
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Petrol station attendants' exposure to vapours of PMS while refueling motor vehicles has led to ill health among these attendants. The implementation of safety policies and practices, enforcement of these policies and provision of PPE is important to safeguard the health of these workers. The objectives of this study were to assess the degree of awareness of safety training and retraining, safety policy enforcement and availability of PPE among petrol pump attendants in Sagamu metropolis and to determine the types of PPE used at work on regular basis. Using random sampling technique, 106 out of 142 petrol station attendants were included (50 males and 56 females) in this study. Data was collected with the use of investigator-administered questionnaires. The data was analyzed with SPSS version 20. Means and standard deviation were used to summarize numerical quantitative variables. Percentages were used to describe categorical variables and tables are used as a method of data presentation. The study showed that majority (63.2%) of filling stations strongly agreed or agreed they were trained and retrained on safety measures. Less than half (47.2%) agreed that petrol station employers actually institute safety measures and put mechanism in place to enforce them. Above a quarter (25.4%) agreed petrol station employers provided enough PPE for petrol pump attendants and less than half of petrol pump attendants use any form of PPE while dispensing petrol. This study has shown that enforcement of existing laws by supervising agencies of government is essential. Enforcement of the use of PPE by petrol station employers will reduce occupational exposure to harmful components of petroleum products and safeguard the health and wellbeing of workers in this important sector of Nigerian economy. This study recommends that 802. Int. J. Health, Safety and Environ. petrol pump employers should be mandated by safety authorities in Nigeria to strengthen training, enforce compliance with safety policies and provide adequate PPE for petrol pump attendants.
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The effect of cuprous oxide and petrol on albino rats was studied using selected parameters associated with rat haematology and semen. The haematological parameters evaluated were Pack cell volume (PCV), Haemoglobin (Hb), Red blood cell (RBC), Mean corpuscular Volume (McV), Mean Corpuscular Haemoglobin (McH) and Mean Corpuscular Haemoglobin Concentration(McHc), while the semen analysis carried out includes; Motility quantitative (M1), Debris quantitative (D1), sperm count (C), morphology primordial (Mp) and morphology structure (Ms). The results revealed the following; Group 1, 2, 3 and 4 had a mean value of 43.0, 31.0, 26.75 and 23.75 respectively for PCV with significant difference (P<0.05) in all the treated groups when compared to the control group. (Hb) had a mean value of 13.65, 9.475, 9.50 and 11.075 for group 1, 2, 3 and 4 respectively with a significant difference (P<0.05) recorded in group 2 and 3 when compared to the control. Group 1, 2, 3 and 4 had a mean value of 4.968, 2.965, 1.63 and 1.815 respectively for red blood cell (RBC) with significant difference (P<0.05) across the groups. A mean value of 8.713, 10.453, 3.45 and 13.655 for group 1, 2, 3 and 4 respectively was recorded for McV with a significant difference (P<0.05) in group all treated group compared to the control. Group 1, 2, 3 and 4 had a mean value of 2.765, 3.450, 5.93 and 5.565 respectively for McH. For McHc, group 1 had a mean value of 0.315 group 2 had 0.305, group 3 had 0.355 and group 4 had 0.483 with a significance difference (P<0.05) recorded for only group 4. In the semen analysis, M1 had mean values of 68.75, 38.75, 28.0 and 27.5 in group 1, 2, 3 and 4 respectively, D1 had 7.5, 11.25, 24.5 and 42.5 in group 1, 2, 3 and 4 respectively, C had 65.0, 52.5, 29.0 and 42.0 in group 1, 2, 3 and 4 respectively while Mp had 7.5, 11.25, 7.5 and 22.5 in group 1, 2, 3 and 4 respectively. The results indicate that cuprous oxide and petrol both have negative effect on the body and hence care should be taken in the storage and handling of petrol to avoid human exposure, also the concentration of cuprous oxide to be used in antifouling paints should be regulated to avoid harming to aquatic organisms.
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Gasoline exposure has been widely reported in the literature as being toxic to human health. However, the exact underlying molecular mechanisms triggered by its inhalation have not been thoroughly investigated. We herein present a model of sub-chronic, static gasoline vapor inhalation in adult female C57BL/6 mice. Animals were exposed daily to either gasoline vapors (0.86 g/animal/90 min) or ambient air for 5 days/week over 7 consecutive weeks. At the end of the study period, toxic and molecular mechanisms underlying the inflammatory, oxidative, and apoptotic effects triggered by gasoline vapors, were examined in the lungs and liver of gasoline-exposed (GE) mice. Static gasoline exposure induced a significant increase (+21%) in lungs/body weight (BW) ratio in GE versus control (CON) mice along with a pulmonary inflammation attested by histological staining. The latter was consistent with increases in the transcript levels of proinflammatory cytokines [Interleukins (ILs) 4 and 6], respectively by ~ 6- and 4-fold in the lungs of GE mice compared to CON. Interestingly, IL-10 expression was also increased by ~ 10-fold in the lungs of GE mice suggesting an attempt to counterbalance the established inflammation. Moreover, the pulmonary expression of IL-12 and TNF-α was downregulated by 2- and 4-fold, respectively, suggesting the skewing toward Th2 phenotype. Additionally, GE mice showed a significant upregulation in Bax/Bcl-2 ratio, caspases 3, 8, and 9 with no change in JNK expression in the lungs, suggesting the activation of both intrinsic and extrinsic apoptotic pathways. Static gasoline exposure over seven consecutive weeks had a minor hepatic portal inflammation attested by H&E staining along with an increase in the hepatic expression of the mitochondrial complexes in GE mice. Therefore, tissue damage biomarkers highlight the health risks associated with vapor exposure and may present potential therapeutic targets for recovery from gasoline intoxication.
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The present study aimed to evaluate the ameliorative effect of red onion extract on fertility in male rabbits that ingested paracetamol and inhaled gasoline. 36 adult male rabbits were used in this study, that divided into 6 groups (n=6): the first group was supplied with drinking water and food, the second was orally gavaged with onion extract (1 ml / 100 gm of body weight per day), the third was inhaled gasoline fumes for two hours daily, the fourth was received orally gavages with 400 mg of paracetamol/kg of body weight daily, the fifth was orally gavaged with paracetamol and then exposed after one hour to gasoline fumes for two hours daily, and the sixth was given the extract of red onion, in addition to given paracetamol, and then exposed after one hour to gasoline fumes for two hours daily for four consecutive weeks. At the end of the experiment and after 24 hours of dosing and exposure, the animals were anesthetized and blood was drawn from them through the heart puncture to measure hormones, and samples were taken from the testicles for histological examination. The results showed that ingestion of paracetamol and inhalation of gasoline fumes leads to serious negative changes in body weight gain, testis weight, sex hormones, semen quality, and testicular histological structure. These alterations increased when animals were exposed to paracetamol and gasoline together. Ingestion of red onion aqueous extract improved all parameters, fertility rate, and histological structure. So, humans who are treated with paracetamol or exposed to gasoline are advice to take red onion aqueous extract to improve their fertility rates
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The current study was conducted to identify the physyological and histological changes in the liver and kidneys of male rabbits induced by inhaling gasoline fumes or ingesting paracetamol or both together. 24 local adult male rabbits were used as experimental animals in this study, which divided into four groups (n = 6). (Control group) In this group, male rabbits were only given drinking water and food for 4 weeks, (Paracetamol group) animals orally received paracetamol (400 mg/kg body weight) daily for 4 weeks, (Gasoline group) in which the male rabbits were exposed to gasoline fumes by inhalation in the exposure chambers for two hours daily for 4 weeks, (Co-administrated paracetamol and gasoline group) animals orally received paracetamol (400 mg/kg body weight) and were subsequently exposed directly to gasoline vapors two hours daily for 4 consecutive weeks. At the end of the experiment, and after 24 hours of dosing and exposure, the animals were anaesthetized and blood was drawn from the heart for biochemical analyses. The animals were dissected after that, and the liver samples were taken for the histological examination. The results showed a significant increase (P <0.01) in the activity of enzymes (ALT, AST, ALP) in the blood serum of rabbits treated with gasoline, paracetamol, and both together compared to the control group, and it also increased significantly (P <0.01) in the gasoline and paracetamol group together. In comparison with the two groups of gasoline and paracetamol, the results showed that the levels of total protein, albumin, and globulin were significantly increased (P<0.01) in the blood serum of gasoline, and paracetamol together, and the total protein and albumin decreased significantly (P<0.05), (P<0.01) respectively In the serum of the paracetamol group and globulin were not significant. compared to the control group, it also increased significantly (P<0.01) in the gasoline and paracetamol group together compared with the gasoline and paracetamol groups. Also, results showed a severe changes in the liver tissue of males rabbits treated with gasoline and paracetamol, and both of them included dilated and congestion of the central veins and blood sinuses, activated Kupffer cells, leukocytic infiltration, increase in thickness of the wall of Blood vesseland bile duct, and congestion in the hepatic portal veins, and these changes were more pronounced in the gasoline and paracetamol group together compared to gasoline and paracetamol groups. The hepatic histological changes confirmed the results that occurred in the biochemical variables in serum, and these changes were more severe in the gasoline and paracetamol group together. Keywords: Gasoline, Paracetamol, Liver function, Hepatic tissues, Male Rabbits.
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Biological monitoring of exposure to bitumen fumes during road-paving operations was carried out. In order to evaluate the biological uptake of the workers, the nonselective urinary thioether assay and a selective method for the determination of urinary 1-hydroxypyrene were used. Urinary thioether data of exposed workers were higher than those of nonexposed subjects. The effect of smoking, however, was stronger than the effect of occupational exposure. Levels of 1-hydroxypyrene in road-paving workers were significantly higher than those in control subjects. The 1-hydroxypyrene level was also influenced by smoking habits, but the effect of occupational exposure was stronger. Our present data suggest that enhanced urine levels of both thioethers and 1-hydroxypyrene in bitumen workers may indicate an increased genotoxic risk. Furthermore, our results demonstrate the applicability of the 1-hydroxypyrene assay after occupational exposure to petroleum-based products.
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Concentrations of glutathione S-transferase (GST; glutathione transferase; EC B1 subunits, F protein, and the activity of alanine aminotransferase (ALT; EC were measured in sequential plasma samples taken from nine patients with self-administered paracetamol (acetaminophen) poisoning. GST exceeded the reference interval in all patients at the time of admission, and F protein was increased in seven. In contrast, abnormal activities of ALT in plasma were found in only one of the nine on admission, a patient admitted 12 h after poisoning. Subsequent to admission nine, eight, and five patients, respectively, had abnormal concentrations of GST, F protein, and ALT. When expressed as multiples of the upper reference limit, the highest values for GST measured in each patient always far exceeded the greatest abnormalities in ALT; this was true for F protein in only five patients. Patients in whom the concentration of GST exceeded 10 micrograms/L on admission subsequently went on to develop moderate or severe liver damage, despite treatment with N-acetylcysteine. F protein and ALT measurements on admission were not as efficient as GST at predicting the clinical outcome of the patients. We conclude that GST and F protein offer clear advantages over ALT for detecting minor degrees of acute liver dysfunction, particularly when only centrilobular damage may be involved.
Administration of carbon tetrachloride to normal rats caused significant decrease in haemoglobin percentage, R.B.C. and W.B.C. counts, however, considerable increase in the levels of transaminases (SGOT and SGPT), blood sugar and activity of alkaline phosphatase observed. Marked increase in the level of serum proteins was also observed. Significant decrease was observed in the glycogen content, activity of alkaline phosphatase and the level of glutathione. On the contrary, considerable increase was observed in the protein content, activity of acid phosphatase and the lipid peroxidation level. PHP-A provided significant protection against most of the biochemical alterations produced by carbon tetrachloride. The degree of protection was maximum at 12 days regimen at 250 mg/kg dose. Oral LD 50 was found to be greater than 2 gm/kg.
Recent studies demonstrated the role of antioxidants in preventing organ damage caused by free radicals. The present study was conducted to find out the modulatory effect of some antioxidants on lipid patterns in experimentally-induced liver damage. Rats chronically intoxicated with carbon tetrachloride (CC14) were used as a model of liver injury terminating with fibrosis or cirrhosis. One hundred and sixty six albino rats were classified into five groups: one served as a control group; the second was subjected to oral administration of CC14 (200 μL/100 g body weight) twice a week; the other three groups, in addition to CC14, received oral doses of silymarin (30mg/kg), vitamin E (200 IU/kg) and vitamin C (50mg/kg) respectively. At the end of the experiment, the animals were killed, blood was collected and liver was taken for histopathological examination. Liver function tests, disturbed by CC14 were significantly modulated by antioxidants, and histopathological examination showed that antioxidants ameliorated the necrotic and fibrotic changes caused by CC14. Treatment with antioxidants was also shown to modulate the toxic effect of CC14 on the lipid profile and malondialdehyde content. Administration of antioxidants could play an important role in prophylaxis against lipid peroxidation and consequently liver fibrosis caused by free radicals.
Many chemical carcinogens require metabolic activation to biologically reactive intermediates which if not detoxified will react with DNA (covalently) or will lesion DNA through the production of reactive oxygen species. The enzymes involved in bioactivation are often phase I enzymes (i.e., those involved in functionalization), while phase II enzymes are involved in conjugation of the functional groups leading to elimination of the carcinogen. Effective elimination can also depend on the presence/absence of transport systems. It is the balance of these events that often determines the carcinogenicity of a chemical in a target tissue and also explains why certain carcinogens give rise to tumors in different organs based on route of administration. In addition, the phase I and phase II enzymes are highly inducible and these genomic responses can determine whether bioactivation or detoxication predominates. Furthermore, many genes involved in these events are highly polymorphic leading to the concept of poor and rapid metabolizers of a particular carcinogen which in turn may govern individual susceptibility to carcinogen exposure.
Heinz body hemolytic anemia developed in Herring Gull (Larus argentatus) nestlings given oral doses of 10 ml of Prudhoe Bay crude oil per kilogram of body weight per day for 5 days. Associated disturbances in red blood cells were increased amounts of reduced glutathione (GSH), peroxidation of membrane lipids, an increase in membrane permeability, and a decrease in the oxygen-carrying capacity of cyanomethemoglobin-convertible hemoglobin. Among groups of gulls given different cumulative doses of oil over a 6-day period, significant covariance with dose and dependence on dose was demonstrated for packed cell volume, hemoglobin, and red cell GSH. Rapid defecation of oil by gulls indicated that the effective dose was substantially less than the administered dose. Pronounced damage to red cells occurred in some birds administered oil for only 2 days. These data imply that the toxic effects of ingested oil may contribute significantly to the morbidity and mortality of oil-contaminated birds.
Levels of glutathione and activity of glutamine synthetase were assayed in organs of rats following inhalation of a heterogeneous solvent mixture containing both aliphatic and aromatic hydrocarbons. This mixture was administered for 3 weeks (6 h daily) at two levels in the inhaled air (400 and 800 ppm) to young adult (5-month-old) and aged (14-month-old) rats. Depression of levels of glutamine synthetase in the P2 fraction of kidney was observed, which was more severe in aged than young adult rats. Glutamine synthetase is a cytosolic enzyme especially susceptible to oxidative damage. A parallel depression of this enzyme was also seen in the corresponding hepatic fractions. However, levels of glutamine synthetase in the hippocampus were elevated by this exposure. Glutathione levels were depressed in P2 fractions of livers of exposed rats, and also in the corresponding renal fraction. Glutathione concentration was unchanged in cerebral fractions. Overall results were interpreted to imply that pro-oxidant events were elevated in kidney and liver following prolonged inhalation of the solvent mixture. The changes found in brain tissue did not reveal evidence of oxidative stress but, however, suggested that glial activation was taking place.
Urine samples from 20 male workers in the polyester industry exposed by inhalation to styrene concentrations ranging from 29 to 41 ppm were investigated. Excretion products of styrene metabolism, mandelic acid and mercapturic acids, were purified from the urine over an extraction column packed with Porapak Q, with subsequent ether elution. The optical enantiomers R- and S-mandelic acid were then determined by thin layer chromatography (TLC) using chiral plate material and selective staining with vanadium pentoxide. Quantitative analysis of these compounds was performed using commercial reference substances. Styrene-specific mercapturic acids were analyzed by a modified TLC method, using synthesized reference substances. The concentration of racemic mandelic acid in the individual urine samples ranged from 80 to 1610 mg/l, and the ratio of the R- and S-enantiomers ranged from 0.7 to 2.2. These individual variations are not explained by differences in individual styrene exposure levels, or by differences in the concentration of the urine samples (in relation to creatinine excretion). Styrene-specific mercapturic acids were detected in the urine of only 1 of the 20 workers, at a concentration much lower than expected from previous investigations by others in humans and laboratory animals, in which less specific analytical methods had been used. The results point to marked interindividual differences in metabolism of styrene, probably related to enzyme polymorphisms.