Protective Effect of Withaferin-A on Micronucleus Frequency and Detoxication Agents During Experimental Oral Carcinogenesis

Our aim was to investigate the effect of Withaferin-A on bone marrow micronucleus frequency and buccal mucosa detoxication agents during 7, 12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in hamsters'' buccal pouches by painting 0.5% DMBA in liquid paraffin, three times per week for 14 weeks. We observed 100% tumor formation in DMBA painted hamsters. Elevated frequency of bone marrow micronucleated polychromatic erythrocytes (MnPCEs) and decrease in buccal mucosa phase II detoxication agents were noticed in tumor bearing hamsters. Oral administration of Withaferin-A significantly reduced the micronucleus frequency and brought back the status of phase II detoxication agents in DMBA painted hamsters. Our study thus demonstrated the protective effect of Withaferin-A on DMBA-induced micronucleus frequency in the bone marrow of golden Syrian hamsters. Also, Withaferin-A maintained the status of buccal mucosa detoxication agents during DMBA-induced hamster buccal pouch carcinogenesis.     

Antitumor initiating potential of rosmarinic acid in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis

Oral cancer accounts for 40%-50% of all cancers in India. Tobacco and alcohol are the major etiological factors contributing to its pathogenesis. The aim of the present study was to explore the key mechanism behind the inhibitory effects of rosmarinic acid against 7,12-dimethylbenz(a)anthracene (DMBA)-induced oral carcinogenesis by evaluating the status of biochemical markers (lipid peroxidation, antioxidants, and detoxification enzymes) and immunoexpression patterns of p53 and bcl-2 proteins. Oral tumors were developed by painting the buccal pouches of golden Syrian hamsters with 0.5% DMBA in liquid paraffin 3 times a week for 14 weeks. We noticed 100% tumor formation in hamsters treated with DMBA alone, and the tumors were histopathologically confirmed as well-differentiated squamous cell carcinoma. Oral administration of rosmarinic acid (100 mg/kg body wt) to DMBA-treated hamsters completely prevented the tumor formation. In addition, rosmarinic acid significantly returned the status of biochemical and molecular markers to near normal range in DMBA-treated hamsters. The results of the present study suggest that rosmarinic acid suppresses oral carcinogenesis by stimulating the activities of detoxification enzymes, improves the status of lipid peroxidation and antioxidants, and downregulates the expression of p53 and bcl-2 during DMBA-induced oral carcinogenesis.     

The potential role of combined antioxidant treatment on pancreas of STZ-diabetic mice

In diabetes, cells and tissues are damaged due to the imbalance between production of free radicals and removal of them. The effective biologic antioxidants for oxidative stress such as α-lipoic acid, vitamin E and selenium are effective in diminishing oxidative damage such as membrane lipid peroxidation. The experiment aimed to investigate the oxidative stress occurring in mitochondrial and cytoplasmic fraction of pancreatic tissues in streptozotocin-diabetic mice and the possible effects of α-lipoic acid + vitamin E + selenium combination on oxidative damage and antioxidative system by using microscopic and biochemical methods.The mice were divided into five groups. These groups were treated by citrate buffer, the solvents of the antioxidants, combined the antioxidants [α-lipoic acid (50 mg/kg), vitamin E (100 mg/kg), selenium (0.25 mg/kg)], streptozotocin (40 mg/kg × 5), combined the antioxidants and streptozotocin. The mice were sacrificed by cervical dislocation.In the experimental group given combined antioxidants following results were observed compared to diabetic group: increased percent insulin-positive cell area; decreased blood glucose levels; increased manganase superoxide dismutase activities and unsignificantly increased superoxide dismutase activities; unsignificantly decreased lipid peroxidase levels in both of fraction; unsignificantly decreased in mitochondrial fraction and unsignificantly increased in cytosolic fraction for catalase levels; not any alteration glutathione levels; not any activity in both of fraction for glutathione peroxidase.We can say that by taking the blood glucose levels and immunohistochemical results into account, the combination of triple antioxidants has a partly positive effect on diabetes. This positive effect could increase when trying different doses of combined antioxidant treatment.     

The effect of rosmarinic acid on 1,2-dimethylhydrazine induced colon carcinogenesis

This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kg b.w.). Groups 3–6 were induced colon cancer by injecting DMH (20 mg/kg b.w.) subcutaneously once a week for the first four weeks (groups 3–6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kg b.w. to groups 4–6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mg kg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kg b.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer.     

Quercetin attenuates the development of 7,12-dimethyl benz(a)anthracene(DMBA) and croton oil-induced skin cancer in mice

To evaluate the chemopreventive potential of quercetin in an experimental skin carcinogenesis mouse model.Skin tumor was induced by topical application of 7,12-dimethyl Benz(a) anthracene(DMBA) and Croton oil in Swiss albino mouse.Quercetin was orally administered at a concentration of 200 mg/kg and 400 mg/kg body weight daily for 16 weeks in mouse to evaluate chemopreventive potential.Skin cancer was assessed by histopathological analysis.We found that quercetin reduced the tumor size and the cumulative number of papillomas.The mean latent period was significantly increased as compared to carcinogen treated controls.Quercetin significantly decreased the serum levels of glutamate oxalate transaminase,glutamate pyruvate transaminase,alkaline phosphatase and bilirubin.It significantly increased the levels of glutathione,superoxide dismutase and catalase.The elevated level of lipid peroxides in the control group was significantly inhibited by quercetin.Futhermore,DNA damage was significantly decreased in quercetin treated mice as compared to DMBA and croton oil treated mice.The results suggest that quercetin exerts chemopreventive effect on DMBA and croton oil induced skin cancer in mice by increasing antioxidant activities.     

Kenaf seed supercritical fluid extract reduces aberrant crypt foci formation in azoxymethane-induced rats

Kenaf (Hibiscus cannabinus) a plant of the family Malvaceae, is a valuable fiber plant native to India and Africa. Kenaf seeds contain alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E and other antioxidants with chemopreventive properties. In the present study we examined the hypothesis that kenaf seed ‘supercritical fluid extract’ (SFE) extract could suppress the early colon carcinogenesis in vivo by virtue of its bioactive compounds. To accomplish this goal, 60 male rats were randomly assigned to 5 groups which were (1) negative control group [not induced with azoxymethane (AOM)]; (2) positive control group (induced with AOM but received no treatment); (3) group treated with 500 mg/kg kenaf seed SFE extract; (4) group treated with 1000 mg/kg kenaf seed SFE extract; (5) group treated with 1500 mg/kg kenaf seed SFE extract. At 7 weeks of age, all rats except the negative control group received 15 mg/kg of AOM injection subcutaneously once a week for 2 weeks. Rats were euthanized at 13 weeks of the experiment. Number of ACF (mean ± SD) ranged from 84.4 ± 4.43 to 179.5 ± 12.78 in group 2, 3, 4, 5. ACF reductions compared with the untreated group were 45.3, 51.4 and 53.1% in rats fed with 500, 1000 and 1500 mg/kg body weight, respectively. There were no significant differences in weight gain among groups. Our finding indicates that kenaf seed SFE extract reduced AOM-induced ACF in Sprague–Dawley male rats.     

Therapeutic potential of Dendrophthoe falcata (L.f) Ettingsh on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in female rats: effect on antioxidant system, lipid peroxidation, and hepatic marker enzymes

In this study, the therapeutic potential of the hydroalcoholic extract of Dendrophthoe falcata (L.f) Ettingsh (Loranthaceae; HEDF) on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma was investigated in Wistar female rats at 55 days of age. Thirty female rats were divided into five groups with six animals in each group: control, DMBA (25 mg in 0.5 ml olive oil by air pouch technique), and DMBA + HEDF (250, 475, and 950 mg/kg). After 90 days of induction, HEDF were administered for 28 days, by gastric intubations. The levels of lipid peroxides and activities of enzymic and nonenzymic antioxidants were measured in serum, liver, kidney, and breast of both control and experimental groups. In addition to this, liver marker enzymes were also assessed. Rats treated with DMBA showed an increase in lipid peroxidation accompanied by high malondialdehyde levels along with lowered activities of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase) and nonenzymic antioxidants (glutathione, ascorbic acid, and α-tocopherol). A significant decrease in alanine aminotransferase, aspartate aminotransferase with a sharp increase in alkaline phosphatase, acid phosphatase, and 5′-nucleotidase was observed in the liver of mammary cancer-bearing animals. HEDF treatment caused the activity of these liver marker enzymes’ return to almost normal control levels. Furthermore, the breast tumor weight decreased significantly in the DMBA + HEDF-treated groups. This result suggests that HEDF shows antioxidant activity and play a protective role against DMBA-induced breast carcinogenesis.     

Influence of rutin on biochemical alterations in hyperammonemia in rats

Flavonoids are non-nutritive dietary components that are widely distributed in plants. The present study was undertaken to examine the protective influence of rutin, a polyphenolic flavonoid, on oxidative stress during ammonium chloride (AC)-induced hyperammonemia by measuring the levels of oxidative damage as well as antioxidant status. The levels of tissue (liver, brain and kidney) lipid peroxides and the antioxidants (total thiols, catalase, reduced glutathione and glutathione peroxidase) were analyzed. Hyperammonemia was induced by daily intraperitoneal injections of AC at a dose of 100 mg/kg body weight for 8 weeks. Decreased levels of tissue lipid peroxidation accompanied with increased antioxidant levels in hyperammonemic rats were observed during oral administration of rutin (50 mg/kg body weight), which clearly shows the antioxidant property of rutin. The study of induction of the antioxidant status is considered to be a reliable marker for evaluating the antiperoxidative effect of the polyphenolic compound. Our present findings show the protective role of rutin against lipid peroxidation and suggest that rutin possesses antioxidant potential that may be used for therapeutic purposes.     

Antihyperglycemic and antioxidant activity of water extract from Anoectochilus roxburghii in experimental diabetes

The hypoglycemic and antioxidant effects of the water extract from Anoectochilus roxburghii in alloxan-induced diabetic mice were examined. Compared with untreated diabetic mice, the daily oral administration of the water extract from A. roxburghii at 0.5 or 2 g/kg for 14 days caused a significant decrease (p < .05) in blood glucose levels with similar effect but no evidence of dose-related effect. Simultaneously, the alteration in lipid metabolism was partially attenuated as evidenced by decreased serum total cholesterol and triglyceride levels and by increased high-density lipoprotein cholesterol concentration in diabetic mice (p < .05) but no dose-related effect was observed. In addition, the water extract from A. roxburghii caused a significant increase (p < .05) in the activities of enzymic antioxidants and the levels of vitamin E in liver and kidney of diabetic mice.Our results suggest that water extract from A. roxburghii possesses hypoglycemic and antioxidant properties after oral administration to mice showing alloxan-induced diabetes.     

A role for prostaglandins in the suppression of cutaneous cellular immunity and tumour development in benzo(a)pyrene- but not dimethylbenz(a)anthracene-treated mice.

Prostaglandins have been implicated in the immune suppression associated with the development of some tumours. Application of the prostaglandin synthetase inhibitor indomethacin, to murine skin prior to treatment with the chemical carcinogens benzo(a)pyrene (BP) or 7,12 dimethylbenz(a)anthracene (DMBA), restored contact sensitivity responses to 2,4-dinitrofluorobenzene in BP- but not DMBA-treated mice. However, indomethacin failed to restore antibody responses in either group of mice. Prolonged treatment with BP or DMBA led to cutaneous tumour formation. Indomethacin was found to delay the onset and reduce the size of tumours in BP- but not DMBA-treated mice. It is proposed that prostaglandin-induced suppression of cellular cutaneous immunity may play a role in BP- but not DMBA-induced cutaneous carcinogenesis.     

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Animal models, namely mice, have been used to study chemically induced carcinogenesis due to their similarity to the histological and genetic features of human patients. Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome. The high incidence of HCC might be related to exposure to known risk factors, including carcinogenic compounds, such as N-nitrosamines, which cause DNA damage. N-nitrosamines affect cell mitochondrial metabolism, disturbing the balance between reactive oxygen species (ROS) and antioxidants, causing oxidative stress and DNA damage, potentially leading to carcinogenesis. This work addresses the progressive histological changes in the liver of N-diethylnitrosamine (DEN)-exposed mice and its correlation with oxidative stress.Male ICR mice were randomly divided into five DEN-exposed and five matched control groups. DEN was IP administered, once a week, for eight consecutive weeks. Samples were taken 18 h after the last DEN injection (8 weeks post-exposure). The following sampling occurred at weeks 15th, 22nd, 29th and 36th after the first DEN injection.DEN resulted in early toxic lesions and, from week 29 onwards, in progressive proliferative lesions. Between 15 and 29 weeks, DEN-exposed animals showed significant changes in hepatic antioxidant (glutathione, glutathione reductase, and catalase) status (p < 0.05) compared with controls. These results point to an association between increased DEN-induced oxidative stress and the early histopathological alterations, suggesting that DEN disrupted the antioxidant defense mechanism, thereby triggering liver carcinogenesis.     

Chemically induced skin carcinogenesis in mice and its prevention by Aegle marmelos (an Indian medicinal plant) fruit extract

This study assessed the chemopreventive potential of the Aegle marmelos plant on mouse skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by croton oil. A significant reduction in tumor incidence, tumor burden, tumor multiplicity, and the cumulative number of papillomas, along with a significant increase in the average latent period, was recorded in mice treated orally with A. marmelos extract (AME) at peri - and post-initiation phases (i.e., 7 days before DMBA application and continued until the end of the experiment) of papillomagenesis as compared with the carcinogen-treated controls. Furthermore, a significant increase in catalase activity, reduced glutathione and total proteins, and a depleted level of lipid peroxidation were observed in liver and skin of AME-treated animals as compared with the carcinogen-treated controls. Thus, the oral administration of AME, at a dose of 50 mg/kg body wt per day per animal, was found to be significantly effective in reducing skin tumors against chemical carcinogenesis in mice.     

Oral phenytoin protects against experimental cyclophosphamide-chemotherapy induced hair loss

In the current study, effects of oral phenytoin on hair growth in cyclophosphamide-treated rats were assessed with the goal of evaluating the ability of phenytoin to suppress chemotherapy-induced hair loss. Thirty-six rats were randomly assigned to six groups (1k6) of six each (n = 6). In all groups, anagen was induced in flank skin of rats by depilation. On day 9 (anagen VI), rats were injected once with either distilled water (groups 1–3) or cyclophoshamide (groups 4–6). From day 10, rats in group 1 and 4 received oral vehicle (distilled water), groups 2 and 5 received oral phenytoin (50 mg/kg), while groups 3 and 6 also received oral phenytoin (100 mg/kg). Drug or vehicle was administered daily for a period of 28 days. The flank area was serially photographed. At the end of the experimental period, rats were sacrificed to correlate visible hair growth with a histological profile of follicle response and recovery. Glutathione (GSH), glutathione peroxidase (GPX) and lipid peroxidation status were assessed. Cyclophosphamide (CYP) treatment was associated with gross morphologic and histological evidence of hair loss in the flanks, microscopic evidence of hair-shaft thinning, increased skin lipid peroxidation, decreased GSH level, and reduction in GPX activities. Phenytoin co-administration was associated with evidence of improved hair growth, increased hair-shaft thickness, reduced skin lipid peroxidation, increased GSH level, and increased GPX activities. This study showed that oral phenytoin can suppress hair loss due to CYP therapy in rats; however, further studies are needed to evaluate its potential application in chemotherapy-induced alopecia.     

Argininic acid alters markers of cellular oxidative damage in vitro: Protective role of antioxidants

We, herein, investigated the in vitro effects of argininic acid on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of 60-day-old rats. We also verified the influence of the antioxidants (each at 1.0 mM) trolox and ascorbic acid, as well as of N^G-nitro-l-arginine methyl ester (L-NAME) at 1.0 mM, a nitric oxide synthase inhibitor, on the effects elicited by argininic acid on the parameters tested. The liver, renal cortex and renal medulla were homogenized in 10 vol (1:10w/v) of 20 mM sodium phosphate buffer, pH 7.4, containing 140 mM KCl; and erythrocytes and plasma were prepared from whole blood samples obtained from rats. For in vitro experiments, the samples were pre-incubated for 1 h at 37 °C in the presence of argininic acid at final concentrations of 0.1, 1.0 and 5.0 μM. Control experiments were performed without the addition of argininic acid. Results showed that argininic acid (5.0 μM) enhanced CAT and SOD activities and decreased GSH-Px activity in the erythrocytes, increased CAT and decreased GSH-Px activities in the renal cortex and decreased CAT and SOD activities in the renal medulla of 60-day-old rats, as compared to the control group. Antioxidants and/or L-NAME prevented most of the alterations caused by argininic acid on the oxidative stress parameters evaluated. Data suggest that argininic acid alters antioxidant defenses in the blood and kidney of rats; however, in the presence of antioxidants and L-NAME, most of these alterations in oxidative stress were prevented. These findings suggest that oxidative stress may be make an important contribution to the damage caused by argininic acid in hyperargininemic patients and that treatment with antioxidants may be beneficial in this pathology.     

Chemopreventive potential of an Indian medicinal plant (Tinospora cordifolia) on skin carcinogenesis in mice.

Tinospora cordifolia (Guduchi), an Indian medicinal plant, was used to explore antitumor promoting activity in a two-stage skin carcinogenesis model. For this purpose, mice were treated by single application of DMBA (100 microg/100 microl of acetone) and two weeks later promoted by croton oil (1% in acetone three times a week) until the end of the experiment (i.e., 16 weeks). Oral administration of the above extract at the preinitiational stage (i.e., seven days before and seven days after DMBA application; group IV), promotional stage (i.e., from the time of croton oil application; group V), and both pre- and postintiational stage (i.e., from the time of DMBA application and continued until the end of the experiment; group VI; on the shaven backs of the mice at the dose of 100 mg/kg body weight/day for 16 weeks) recorded significant reduction in tumor weight, tumor incidence in comparison to control (i.e., mice treated with DMBA and croton oil; group III). Furthermore, cumulative number of papillomas, tumor yield, tumor burden, and tumor weight showed significant reduction along with significant elevation of phase II detoxifying enzymes, and inhibition of lipid peroxidation in liver and skin in the animals administered with such plant extract concomitant to carcinogen exposure. Thus, the present data strongly suggests that the Tinospora cordifolia extract has anti-tumor potential in a two-stage skin carcinogenesis mouse model.     

Absence of chemopreventive influence of propolis on the rat liver altered foci development

Propolis (bee glue) is a complex mixture of natural substances that exhibits a broad spectrum of biological activities. As the possibility exists that it may exert a chemopreventive role against cancer development, the present study aimed to evaluate the chemopreventive influence of a Brazilian aqueous propolis extract (APE) in a rat two-stage (initiation-promotion) medium-term bioassay for chemical liver carcinogenesis. Male Wistar rats were sequentially initiated with diethylnitrosamine (DEN, 200 mg/kg b.w.) and, 2 weeks later, exposed to a diet containing hexachlorobenzene (HCB, 100 ppm) and to APE 0.1% through drinking water for 6 weeks. Appropriate control groups were also established. The animals were sacrificed at the weeks 8th and 30th when liver samples were processed to evaluate the development of altered hepatocyte foci (AHF) identified under hematoxylin and eosin (H&E) staining and by the immunohistochemical expression of the enzyme glutathione S-transferase placental form (GST-P). The results indicate that APE 0.1% did not protect against the development of any of the differentially identified putative preneoplastic foci in DEN-initiated animals, exposed or not to the promoting agent HCB. Also, APE 0.1% by itself did not significantly induce any AHF, what is in line with its already known absence of genotoxic potential. Our results indicate that an aqueous extract of Brazilian propolis did not exert chemoprevention on the hepatocarcinogenesis process chemically induced in the rat.     

Genistein and daidzein, in combination, protect cellular integrity during 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis in Sprague-Dawley rats

The status of glycoconjugates (protein bound hexose, hexosamine, sialic acid and fucose) in plasma or serum serve as potential biomarkers for assessing tumor progression and therapeutic interventions. Aim of the present study was to investigate the protective effect of two major soy isoflavones, genistein and daidzein, in combination on the status of glycoconjugates in plasma, erythrocyte membrane and mammary tissues during 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis in female Sprague-Dawley rats. A single subcutaneous injection of DMBA (25 mg rat(-1)) in the mammary gland developed mammary carcinoma in female Sprague-Dawley rats. Elevated levels of plasma and mammary tissue glycoconjugates accompanied by reduction in erythrocyte membrane glycoconjugates were observed in rats bearing mammary tumors. Oral administration of genistein + daidzein (20 mg + 20 mg kg(-1) bw/day) to DMBA treated rats significantly (p< 0.05) brought back the status of glycoconjugates to near normal range. The present study thus demonstrated that genistein and daidzein in combination protected the structural integrity of the cell surface and membranes during DMBA-induced mammary carcinogenesis.     

Response of liver to lipopolysaccharide treatment in male and female rats

Gender is considered to be an important factor in endotoxin-induced tissue damage. Our aim was to examine the role of sex on the prooxidant–antioxidant status, necrotic and apoptotic events in the liver of lipopolysaccharide (LPS)-treated rats. We determined levels of lipid peroxides, non-enzymatic and enzymatic antioxidants, and expressions of apoptosis-related proteins, antiapoptotic B cell lymphoma-2 (Bcl-2) and proapoptotic Bax, caspase-3 activity and apoptotic cell numbers in the liver. Hepatic histopathology and serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were also investigated. Male and female Wistar rats (180–200 g) were injected with LPS (10 mg/kg, i.p.) and examinations were performed 6 h after the injection. Significant increases in hepatic thiobarbituric acid reactive substances and diene conjugate levels were observed in male and female rats following LPS treatment. However, there were no changes in hepatic glutathione, vitamin E and vitamin C levels together with superoxide dismutase, glutathione peroxidase and glutathione transferase activities. LPS treatment caused significant increases in serum ALT and AST activities and lymphocyte infiltration and necrotic changes in the livers. Bcl-2 and Bax expressions, caspase-3 activity and apoptotic cell numbers were also found to be increased in both groups. In conclusion, no sex-dependent difference was observed in the changed hepatic prooxidant–antioxidant status of rats following LPS treatment. Besides, the process leading to apoptosis and necrosis in the liver showed a similar pattern in both gender of rats.     

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5 mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50 mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50 mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.