Genome-wide miRNA-profiling of aflatoxin B1-induced hepatic injury using deep sequencing

Aflatoxin B1 is a potent carcinogen which can induce** hepatocellular carcinoma (HCC) in mammals. Though microRNAs are known to play important roles in tumorigenesis, the functional complexity of microRNAs in AFB1-induced hepatocellular tumorigenesis has not yet been elucidated. Here, we applied Illumina deep sequencing technology for high-throughput profiling of microRNA in rat liver tissue before and after treatment with aflatoxin B1. Analysis of mature miRNAs from different arms of pre-miRNAs allowed us to identify the predominant form of miRNA. We studied the differential expression profile of miRNAs in two libraries, identifying several cancer-related microRNAs which exhibit abnormal expression. KEGG analysis indicated that predicted target genes of differentially expressed miRNAs are involved in cancer-related pathways. Bioinformatic analysis predicted 16 potential novel miRNAs. Our work provides new insights at the miRNA level into AFB1-induced hepatic injury which may lead to HCC.     

A 13-week oral dose subchronic toxicity study of gardenia yellow containing geniposide in rats.

Gardenia yellow powders A, B and C, containing geniposide at 0.284%, 0.938% and 2.783%, respectively, were administered orally to male and female SD rats as 3% feed admixtures for 13-weeks to evaluate any potential toxicity. Mean geniposide intake values were 5.72, 18.9 and 56.3mg/kg/day in groups receiving these feed admixtures, respectively. All animals survived the duration of the study. The following findings were evident in the gardenia yellow C group: chromatouria, slightly increased plasma total bilirubin, blackish brown discoloration of the kidneys and liver, brown pigments in the proximal tubular epithelium of the kidneys. Slightly increased plasma total bilirubin was considered to be due to interference of metabolite of geniposide with the system of measurement and not to be a toxic effect since there were no related changes in histopathology of the liver or in any blood chemistry parameters. Other findings were limited to pigmentations or discolorations attributable to metabolites of geniposide. No treatment-related effects were evident on body weight, food consumption, ophthalmology, hematology or organ weights in any group. Therefore, it was concluded that 3-month ingestion of the gardenia yellow powder containing geniposide at 2.783% (approximately 60 mg/kg/day as geniposide intake) does not cause any severe toxic effects.     

Subchronic toxicity studies with ginsenoside compound K delivered to dogs via intravenous administration

Compound K, i.e., 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol, is the main metabolite of the protopanaxadiol type of ginseng saponin produced by intestinal bacteria after oral administration of ginseng extract. In the present study, the toxicity of compound K was evaluated in male and female dogs after 90 days continuous intravenous infusion. Beagle dogs were treated with compound K at doses of 6.7, 20 and 60 mg/kg/day, and observed for 90 days followed by recovery periods. Measurements included clinical observations, body weight, food consumption, temperature, electrocardiogram (ECG), hematology, blood chemistry, urinalysis, gross necropsy, organ weight and histopathology. Under the conditions, the clinical condition of the animals, body weights, body weight gains and food consumption were unaffected by compound K administration relative to the control group. Hematology, ECG data and urinalysis parameters were also unaffected. However, the hepatotoxicity was evident from the observation of multiple parameters, including histopathological evaluation of liver tissue upon necropsy as well as large increases in plasma levels of liver enzymes (alanine aminotransferase, ALT, Gamma-glutamyltranspeptidase, γ-GT, alkaline phosphatase,ALP) in groups receiving compound K (20 or 60 mg/kg/day), and this hepatoxicity might be reversible. In addition, the NOAEL of compound K is 6.7 mg/kg/day in this 90 days toxicity study.     

Safety assessment of astaxanthin-rich microalgae biomass: Acute and subchronic toxicity studies in rats

Astaxanthin, a natural nutritional component, is marketed as a dietary supplement around the world. The primary commercial source for astaxanthin is Haematococcus pluvialis (microalgae). The objective of the present study was to investigate the acute and subchronic toxicity of an astaxanthin-rich biomass of H. pluvialis (AstaCarox((R))). The oral LD(50) of the biomass in rats was greater than 12g/kg body weight. In the subchronic study, Wistar rats (10/sex/group) were fed diets containing 0%, 1%, 5% and 20% of the biomass (weight/weight) for 90 days. trans-Astaxanthin was quantifiable in the plasma of the high-dose treated group only. Compared to the control group, no treatment-related biologically significant effects of astaxanthin were noted on body weight or body weight gain. Biomass feeding did not affect hematological parameters. In the high-dose group, slightly elevated alkaline phosphatase and changes in some urine parameters and an increase in kidney weight in both sexes were noted. Histopathology examinations did not reveal adverse effects except for a marginal increase in pigment in the straight proximal tubule of the kidney in 5/10 female rats treated with the high-dose. These changes were not considered as toxicologically significant. Although the rats in high-dose group received about 9% more fat, it is unlikely that this confounding factor significantly altered the outcome. The no-observed adverse-effect-levels (NOAEL) of the astaxanthin-rich biomass for male and female rats were determined as 14,161 and 17,076mg/kg body weight/day, or 465 and 557mg astaxanthin/kg/day, respectively, the highest dose tested.     

Propetamphos-induced changes in haematological and biochemical parameters of female rats: Protective role of propolis

The present study was conducted to investigate the effectiveness of propolis in alleviating the toxicity of propetamphos on haematological and biochemical parameters in rats. Twenty-four female Wistar–Albino rats (200–250 g) were randomly divided into four equal groups of six rats each. As normal drinking water was given to the control group, propolis (100 mg/kg bw/day), propetamphos (15 mg/kg bw/day), and propolis (100 mg/kg bw/day) with propetamphos (15 mg/kg bw/day) combinations were given to the other three groups by adding to drinking water for 28 days, respectively.     

Lack of toxic effect of technical azadirachtin during postnatal development of rats.

Azadirachtin, a biopesticide has been evaluated for its possible toxic effects during postnatal development of rats over two generations. Rats were fed 100, 500 and 1000ppm technical azadirachtin through diet which is equivalent to 5, 25 and 50mg/kg body weight of rats. Technical azadirachtin has not produced any adverse effects on reproductive function and data were comparable to control animals over two generations. There were no toxicological effect in parent rats as evidenced by clinical signs of toxicity, enzymatic parameters like AST, ALT, ALP, S. bilirubin, S. cholesterol, total protein and histopathology of liver, brain, kidney and testes/ovary. The litters of F(1B) and F(2B) generations were devoid of any morphological, visceral and teratological changes. The percent cumulative loss and growth index of pups were also comparable to respective controls in successive growth period of 0, 4, 7, 14 and 21 days in two generations. There were no major malformations in fetuses while some insignificant minor skeletal variations like missing 5th sternebrae and bipartite thoracic centre found were not compound or dose related. No significant pathomorphological changes were observed in liver, kidney, brain and gonads of F(2B) pups. In conclusion rats fed technical azadirachtin showed no evidence of cumulative effects on postnatal development and reproductive performance over two generations. Absence of any major adverse reproductive effects in adults as well as in 21 days old pups of F(2B) generation suggest the safe use of technical azadirachtin as a biopesticide.     

Selective impairment of drug-metabolizing enzymes in pig liver during subchronic dietary exposure to aflatoxin B1.

Consequences of subchronic exposure to aflatoxin B1 (AFB1) on liver monooxygenase and transferase enzymes were compared in control pigs and pigs given 385, 867 or 1,807 microg AFB1/kg of feed for 4 weeks. Animals exposed to the highest dose of toxin developed clinical signs of aflatoxicosis, like liver fibrosis, hepatic dysfunction and decreased weight gain. This group had significantly lower levels of liver cytochrome P450, ethoxyresorufin O-deethylase (EROD) activity, testosterone metabolism, P450 1A and P450 3A protein expression. By comparison, mild degenerative hepatic changes, no hepatic dysfunction but a similar pattern of liver P450 enzymes activity without changes in P450 3A expression were observed in pigs exposed to 867 microg AFB1/kg of feed. Benzphetamine and aminopyrine N-demethylase activities were increased in pigs exposed to 867 or 1,807microg AFB1/kg of feed. Pigs exposed to 385 microg AFB1/kg of feed had low levels of EROD activity and all other biotransformation and clinical parameters remained at control levels. Aniline hydroxylase activity, P450 2C protein expression, UDP-glucuronosyl and glutathione S-transferase activities were unaffected at all doses of AFB1. In conclusion, P450 1A and P450 3A appear to be specific targets of AFB1 even if pig did not display clinical sign of liver toxicosis.     

Amelioration of anti-cancer agent adriamycin-induced nephrotic syndrome in rats by Wulingsan (Gorei-San), a blended traditional Chinese herbal medicine

Anti-cancer agent adriamycin (ADR) has demonstrated high anti-tumor efficacy. However, its use in chemotherapy has been limited largely due to its diverse toxicities, including renal toxicity, such as nephrotic syndrome with proteinuria. Podocyte injury leads to glomeruli proteinuria. Wulingsan (WLS) is a blended traditional Chinese herbal medicine specifically used for various kidney diseases. In the present study, we found that a water extract of WLS (480 mg/kg, p.o., x 28 days) reduced ADR-induced increase in urine protein excretion, plasma total cholesterol and triglyceride, and decrease in plasma total protein and albumin in rats. Furthermore, the results of electron microscopy demonstrated suppression by WLS of ADR-induced increase in width of foot process, increase in surface density and decrease in volume density. These results suggest that WLS ameliorates ADR-induced proteinuria and podocyte injury. Gene analysis results demonstrated a suppression of renal overexpression of nephrin mRNA and protein by WLS. Radioimmunoassay showed that WLS suppressed ADR-induced increased renal angiotensin II content in rats. Thus our results demonstrate that WLS ameliorates ADR-induced nephrotic syndrome in rats possibly by suppressing ADR-induced hyperactivity of renal renin-angiotensin system to modulate renal nephrin gene expression, thereby protecting podocyte from injury.     

Thioacetamide-induced cirrhosis in selenium-adequate mice displays rapid and persistent abnormity of hepatic selenoenzymes which are mute to selenium supplementation

Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes up and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels.     

Toxicological evaluation of the effect of water contaminated with lead,phenol and benzene on liver,kidney and colon of Albino rats

The effect of water contaminated with phenol, benzene and lead on rats cellular system was investigated. Selected enzyme activity of the kidney and colon of rats was carried out. Standard enzyme assays were also conducted for selected liver enzymes such as alkaline and acid phosphatases, alanine and aspartate transaminases, and gamma glutamyl transpeptidase. Serum indices of liver and kidney function were also determined. The direct bilirubin of test rats were observed to be 3.2 ± 0.2 U/mol/l while that of control rat was 1.2 ± 0.003 U/mol/l. The total bilirubin of test rats was found to be 8.4 ± 0.8 U/mol/l while that of the control was 5.6 ± 0.5 U/mol/l. Generally, enzymes activity in the tissues of test rats were found to be significantly (p < 0.05) lower relative to control, while the enzyme activity of the serum of test rats was significantly (p < 0.05) higher than control. It could be inferred that experimental data suggest possible damage to the tissues and that consumption of polluted water may account for increasing cases of renal and hepatic failure among people in developing countries.     

Safety assessment of a solid lipid curcumin particle preparation: Acute and subchronic toxicity studies

Curcumin, a polyphenol, is obtained from turmeric, the ground rhizomes of Curcuma longa L. Extensive research over the past half century has revealed several health benefits of curcumin. The objective of the present study was to investigate potential adverse effects, if any, of a novel solid lipid curcumin particle (SLCP) preparation in rats following acute and subchronic administration. The oral LD₅₀ of the preparation in rats as well as in mice was found to be greater than 2000 mg/kg body weight (bw). In the subchronic toxicity study, Wistar rats (10/sex/group) were administered via oral gavage 0 (control), 180, 360, and 720 mg/kg bw/day of SLCP preparation for 90 days. Administration of the curcumin preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No adverse effects of the curcumin preparation were noted on the hematology, serum chemistry parameters, and urinalysis. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for this standardized novel curcumin preparation was determined as 720 mg/kg bw/day, the highest dose tested.     

Assessment of candidate biomarkers of drug-induced hepatobiliary injury in preclinical toxicity studies

This study was designed to assess the value of a set of potential markers for improved detection of liver injury in preclinical toxicity studies. Male Wistar rats were treated with drug candidates (BAY16, EMD335823, BI-3) that previously failed during development, in part due to hepatotoxicity, at two dose levels for 1, 3 and 14 days. Concentrations of lipocalin-2/NGAL and clusterin, which are frequently overexpressed and released from damaged tissues, and thiostatin, recently identified within PredTox as being elevated in urine in response to liver injury, were determined in rat urine and serum by ELISA. This was supplemented by confirmatory qRT-PCR and immunohistochemical analyses in the target organ. Serum paraoxonase-1 activity (PON1), which has been suggested as a marker of hepatotoxicity, was determined using a fluorometric assay. Clusterin and PON1 were not consistently altered in response to liver injury. In contrast, thiostatin and NGAL were increased in serum and urine of treated animals in a time- and dose-dependent manner. These changes correlated well with mRNA expression in the target organ and generally reflected the onset and degree of drug-induced liver injury. Receiver–operating characteristics (ROC) analyses supported serum thiostatin, but not NGAL, as a better indicator of drug-induced hepatobiliary injury than conventional clinical chemistry parameters, i.e. ALP, ALT and AST. Although thiostatin, an acute phase protein expressed in a range of tissues, may not be specific for liver injury, our results indicate that thiostatin may serve as a sensitive, minimally-invasive diagnostic marker of inflammation and tissue damage in preclinical safety assessment.     

Levels of transaminases, alkaline phosphatase, and protein in tissues of Clarias gariepienus fingerlings exposed to sublethal concentrations of cadmium chloride

The freshwater fish, Clarias gariepienus fingerlings, were exposed to sublethal concentrations (1.7 and 3.4 mg/L) of cadmium chloride for 12 days. Aspartate aminotransferase (AAT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total protein levels were assayed in the gill, brain, and muscle of the fish at regular intervals of 6 and 12 days. The activities of AAT, ALT, and ALP of the treated fishes increased significantly in all the tissues compared with the control fish. Protein level in all the tissues showed a significant decrease in comparison to unexposed controls throughout the experimental periods. These results revealed that cadmium chloride effects the intermediary metabolism of C. gariepienus fingerlings and that the assayed enzymes can work as good biomarkers of contamination.     

Safety assessment of lutein and zeaxanthin (Lutemax™ 2020): Subchronic toxicity and mutagenicity studies

Lutein and zeaxanthin, naturally occurring carotenoids, have shown to reduce the risk of cataracts and age-related macular degeneration. Lutemax™ 2020 is a lutein and zeaxanthin (including meso-isomer) enriched product obtained from Marigold flowers (Tagetes erecta L). The objective of the present study was to investigate adverse effects, if any, of Lutemax 2020™ in acute and subchronic toxicity, and mutagenicity studies. In acute toxicity study in rats no lethality was noted at 2000 mg Lutemax 2020™/kg body weight (bw). In the subchronic study, Wistar rats (10/sex/group) were administered (gavage) lutein/zeaxanthin concentrate at dose levels of 0, 4, 40 and 400 mg/kg bw/day for 90-days. Compared with the control group, administration of lutein/zeaxanthin concentrate did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No toxicologically relevant findings were noted in urinalysis, hematology or clinical biochemistry parameters at the end of the treatment or recovery period. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. The results of mutagenicity testing in Salmonella typhimurium did not reveal any genotoxicity. The no observed-adverse-effect level (NOAEL) for lutein/zeaxanthin concentrate was determined as 400 mg/kg bw/day, the highest dose tested.     

A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters.

Assessing liver damage in basic toxicology research and in preclinical toxicity testing is usually evaluated by serum biochemical parameters prior to confirmation by histopathology. With the advent of newer methods such as genomics and proteomics, there is increased enthusiasm to generate "novel" predictive markers to detect liver pathology even before the alterations in clinical and histopathology parameters occur. However, serum biochemical parameters (clinical pathology) when employed accurately, can provide important and useful information in assessing not only the extent and severity of liver damage, but also the type of liver damage (membrane injury versus cholestasis and hepatic function). In order to accurately detect hepatobiliary pathologies, it is important to have a basic understanding of liver associated clinical pathology parameters with reference to their exact location, serum half-lives, tissue concentration gradient and species differences. Such understanding as discussed in this article will enable a toxicologist to identify commonly encountered toxic hepatic lesions such as necrosis, cholestasis and compromised liver function by hepatic-associated clinical pathology parameters. In addition, toxicologists will have a better grasp to effectively communicate their clinical pathology findings and interpretations to the target audiences.     

Effect of aflatoxin B1 on hepatic drug-metabolizing enzymes in female rats. Interaction with a contraceptive agent

1. The effect of a contraceptive on aflatoxin B1 toxicity has been studied in female rats treated for 15 consecutive days with repeated doses of aflatoxin (0.40 mg/kg/day), norethindrone (0.60 mg/kg/day) and ethynylestradiol (0.012 mg/kg/day). 2. Increases occurred in hepatic microsomal cytochrome P-450 content (31%), and in the activities of epoxide hydrase (77%), UDP-glucuronyltransferase (67%) and gamma-glutamyltransferase (78%). 3. Aflatoxin alone caused a 22% increase in GSH S-epoxide transferase activity, whereas the contraceptive given alone or combined with aflatoxin increased the hepatic reduced glutathione. 4. The effect of aflatoxin plus contraceptive was not additive. 5. The effects caused by aflatoxin and the contraceptive were similar, and the contraceptive (depending on its progestogen/estrogen ratio), may modify aflatoxin toxicity by increasing the drug-metabolizing enzyme activities and the concentration of hepatic glutathione.     

Safety studies of pseudo-ceramide SLE66: Acute and short-term toxicity

Topical application of ceramides is reported to improve the structure and texture of the skin. Synthetic pseudo-cermaide, SLE66 has been shown to reduce dryness/scaling/itching of human skin. Although efficacy of topically applied ceramides and their analogs has been investigated to some extent, safety information is scarce. The objective of the present investigation was to evaluate potential adverse effects of SLE66. The oral LD₅₀ of SLE66 in rats and mice was >5000 mg/kg, while dermal LD₅₀ in rats was >2000 mg/kg. In animal and human studies, SLE66 did not cause skin irritation or sensitization. SLE66 does not possess phototoxicity or photosensitization potentials. Instillation of SLE66 into rabbit eye elicited transient conjunctival irritation. In 28 day repeat-dose studies, administration of SLE66 via gavage (daily) or by dermal application (five days/week) to Sprague Dawley rats at levels up to 1000 mg/kg/day did not cause mortality or morbidity. Compared to the controls, the clinical condition of the animals, body weights, feed consumption, hematology, clinical chemistry, organ weights, and gross necropsy findings were unaffected by oral or dermal administration of SLE66. The no-observed-adverse-effect level (NOAEL) for systemic toxicity following oral or dermal administration of SLE66 was 1000 mg/kg/day (the highest level tested).     

Toxicological evaluation of chronic exposure to the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one in male rats

The aim of this study was to evaluate the effect of chronic treatment with the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some behavioral and biochemical parameters in the brain, liver, kidney and serum of 90-day-old male Wistar rats. The animals received the organoselenium at doses of 125, 250 or 500 μg/kg body weight intraperitoneally once daily for 30 days. Results showed that chronic treatment with this compound induced behavioral changes in animals, such as increasing of rearing at dose of 250 μg/kg and increasing of ambulation in all concentrations tested. On the other hand, we did not observe any alterations in the body weight gain of the animals. Moreover, the activity of the enzyme creatine kinase (CK) decreased in the cerebral cortex, cerebellum and kidney and increased in the liver after the chronic treatment with the organoselenium compound at dose of 500 μg/kg. The compound also increased aspartate aminotransferase (AST) and urea levels in serum of rats at 500 μg/kg. Glucose, cholesterol, triglycerides, creatinine, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were not changed by the treatment. Our results thus show that chronic administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one is able to significantly change the activity of CK in Wistar rats, resulting in a change in cellular energy homeostasis in these tissues, liver damage and behavioral changes in the animals studied.     

Circulating microRNA profiles altered in mice after 28 d exposure to perfluorooctanoic acid

Perfluorooctanoic acid (PFOA) is a stable man-made compound with many industrial and commercial uses. Recently, however, concern has been raised that it may induce various toxicological effects such as hepatotoxicity, immunotoxicity, and developmental toxicity. Because levels of circulating microRNAs (miRNAs) can be altered in several clinical diseases, they may serve as potential novel biomarkers. Here, we explored differences in the profiles of circulating miRNAs in mice after PFOA exposure. Using TaqMan miRNA arrays, we determined that the levels of 24 circulating miRNAs were altered in mice dosed with PFOA at 1.25 mg/kg/d and 73 were altered in mice dosed with 5 mg/kg/d. Eight miRNAs were further validated using TaqMan Real-Time PCR assays. Results were consistent with those obtained from the TaqMan miRNA arrays, except for miR-199a-3p. The most remarkable of the circulating miRNAs (miR-26b-5p and miR-199a-3p) were also up-regulated in the serum of occupational workers in our previous epidemiological study. We also found similar patterns in mice exposed to PFOS. These results demonstrated that circulating miRNA profiles were altered after exposure to high concentrations of PFOA and miR-28-5p, miR-32-5p, miR-122-5p, miR-192-5p, and miR-26b-5p in serum may be linked to effects of PFOA, especially in occupationally exposed people.     

Hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats

The present study was carried to evaluate the hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot and its kernel against ethanol-induced oxidative stress. The hepatopreventive and antioxidant potential of the plant’s supplementations were evaluated by measuring level of serum liver damage marker enzymes (AST, ALT, GGT and LDH), antioxidant defense systems (GSH, GR, SOD, GST and GPX) and MDA content in various tissues of rats. Eight experimental groups: I (control), II (20% ethanol), III (ethanol + 15% sun-dried apricot), IV (ethanol + 30% sun dried). V (ethanol + 15% sulphited-dried), VI (ethanol + 30% sulphited-dried), VII (ethanol + 15% kernel) and VIII (ethanol + 30% kernel). According to the results, the levels of serum enzymes increased significantly in the II group as compared to those of I group, but they decreased in the III, IV, V and VI groups as compared to those of II group. Also, administration of sun and sulphited-dried apricot supplementation restored the ethanol-induced imbalance between MDA and antioxidant system towards near normal particularly in tissues but not its kernel. It is concluded that apricot has a hepatoprotective effect in rats with ethanol, probably acting by promoting the antioxidative defense systems.