Toxicity of methimazole on femoral bone in suckling rats: Alleviation by selenium

AimsSelenium has a pharmacological properties and it is well considered as an antioxidant. The present study investigated the potential ability of selenium, used as a nutritional supplement, to alleviate bone impairments in suckling rats whose mothers were treated with methimazole, an antithyroid drug.Main methodsFemale Wistar rats were randomly divided into four groups of six each: group I served as control which received standard diet; group II were rendered hypothyroid by administration of methimazole (250 mg L^?1 in their drinking water); group III received both methimazole (250 mg L^?1 in their drinking water) and selenium (0.5 mg kg^?1 of diet); group IV received 0.5 Na₂SeO₃ mg kg^?1 of diet. Treatments were started from the 14th day of pregnancy until day 14 after delivery.Key findingsMethimazole treatment decreased femur length and weight in 14-day-old rats, when compared to controls. Femur antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high femur malondialdehyde levels. Methimazole also caused a significant decrease in calcium and phosphorus levels in bone. Yet, in plasma and urine, they increased and decreased inversely. Besides, plasma total tartrate-resistant acid phosphatase was enhanced, while total alkaline phosphatase was reduced. Co-administration of selenium through diet improved the biochemical parameters cited above. Nevertheless, distorted histoarchitecture revealed in hypothyroid rat femur was alleviated by Se treatment.SignificanceThe present study suggests that selenium is an important protective element that may be used as a dietary supplement protecting against bone impairments.     

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.     

Preventive effect of a galactoglucomannan (GGM) from Dendrobium huoshanense on selenium-induced liver injury and fibrosis in rats

This study was carried out to investigate the preventive effects of galactoglucomannan (GGM), a homogeneous polysaccharide from Dendrobium huoshanense, on liver injury and fibrosis induced by sodium selenite. Sprague–Dawley rats injected subcutaneously with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. were set as the model groups. Rats treated with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. and GGM at 50–200 mg kg^?1 b. wt. were set as the prevention groups. Biochemical and histological analysis showed that GGM significantly ameliorated selenite-induced liver injury and fibrosis in rats. Oral administration of GGM effectively attenuated the toxicity of selenite to liver tissue, which was judged both by the decreased activities of serum hepatic enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and by liver histopathological examination. Meanwhile, GGM also reduced the levels of H₂O₂ and malondialdehyde (MDA), elevated the levels of GSH, restored the fluidity of hepatic plasma membrane, and retained the activities of endogenous enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). The prevention of selenite-induced liver injury and fibrosis by GGM was further supported by the reduced expression of transforming growth factor-β1 (TGF-β1) and type I collagen. These results suggested that GGM may be developed into a novel antifibrotic agent for the prevention of liver injury and fibrosis.     

Toxico-pathological changes induced by cypermethrin in broiler chicks: Their attenuation with Vitamin E and selenium

Ninety 1-day old broiler chicks of mixed gender (as hatched) procured from a local hatchery were randomly divided into five equal groups. All the treatments were given through crop tubing. Groups 1–4 received cypermethrin (CY) (600 mg kg^?1 b. wt.) daily for 30 days. In addition to CY (group 1), groups 2–4 received Vit E (150 mg kg^?1 b. wt.), Se (0.25 mg kg^?1 b. wt.), and Vit E (150 mg kg^?1 b. wt.)+Se (0.25 mg kg^?1 b. wt.), respectively. Group 5 served as control andreceived normal saline (2 ml kg^?1 b. wt.) for 30 days. Randomly selected six broiler chicks from each group were slaughtered at experimental days 10, 20 and 30 for the collection of serum/plasma and morbid tissues. Absolute organ weights were recorded. Total plasma proteins, fibrinogen and creatinine were significantly (P<0.05) increased while alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and urea decreased significantly (P<0.05) in CY-treated group when compared with the control group. Kidneys were swollen grossly in treated broiler chicks. In liver, necrosis of hepatocytes, cytoplasmic vacuolation, bile duct hyperplasia and mononuclear cellular infiltration were observed. In kidneys, necrosis of tubular epithelial cells, cytoplasmic vacuolation, cellular infiltration and atrophy of glomeruli were observed. Sub-arachnoid space was much dilated in CY-treated broiler chicks. It can be concluded that CY induces biochemical and histopathological alterations in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective in ameliorating toxic effects of cypermethrin in broilers chicks.     

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats

The present study was to evaluate the hepatoprotective effect of hesperetin (HTN) on cadmium (Cd) induced hepatotoxicity in male Wistar rats. Administration of Cd (3 mg/kg body weight/day) subcutaneously for 21 days, the levels of hepatic markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and bilirubin were significantly increased in serum. The levels oxidative stress markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and protein carbonyl content (PCC) were also significantly increased while the levels of vitamin C, vitamin E, reduced glutathione (GSH), total sulphydryl group (TSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) were significantly decreased in the liver of Cd intoxicated rats. HTN, a flavanone in citrus fruits, administrated orally along with Cd injection for 21 days, significantly revert back the status of serum hepatic markers, oxidative stress markers and antioxidant markers in the liver tissue to near normal level in a dose dependent manner. HTN at a dose of 40 mg/kg body weight/day exhibits significant (p < 0.05) hepatoprotection compared with other two doses (10 and 20 mg/kg body weight/day). The histopathological studies in the liver of rats also supported that HTN (40 mg/kg) markedly reduced the toxicity of Cd and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that HTN acts as a potent hepatoprotective agent against Cd induced hepatotoxicity in rats.     

Puerarin protects the rat liver against oxidative stress-mediated DNA damage and apoptosis induced by lead

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. In this study, we valuated the protective effect of puerarin against lead-induced oxidative DNA damage and apoptosis in rat liver. A total of forty male Wistar rats (8-week-old) was divided into 4 groups: control group; lead-treated group (500 mg Pb/l as the only drinking fluid); lead + puerarin treated group (500 mg Pb/l as the only drinking fluid plus 400 mg PU/kg bwt intra-gastrically once daily); and puerarin-treated group (400 mg PU/kg bwt intra-gastrically once daily). The experimental period was lasted for 75 successive days. Our data showed that puerarin significantly effectively improved the lead-induced histology changes in rat liver and decreased the serum ALT and AST activities in lead-treated rats. Puerarin markedly restored Cu/Zn-SOD, CAT and GPx activities and the GSH/GSSG ratio in the liver of lead-treated rat. Furthermore, the increase of 8-hydroxydeoxyguanosine induced by lead was effectively suppressed by puerarin. The enhanced caspase-3 activity in the rat liver induced by lead was also inhibited by puerarin. TUNEL assay showed that lead-induced apoptosis in rat liver was significantly inhibited by puerarin, which might be attributed to its antioxidant property. In conclusion, these results suggested that puerarin could protect the rat liver against lead-induced injury by reducing ROS production, renewing the activities of antioxidant enzymes and decreasing DNA oxidative damage.     

Folic acid induces acute renal failure (ARF) by enhancing renal prooxidant state

Systemic administration of folic acid (FA) in mice was used for studying the pathogenesis associated with acute renal failure (ARF). However, the mechanism by which FA induces ARF remains poorly understood. The present study therefore, was planned to investigate the effect of folic acid administration on prooxidant state and associated ultrastructural changes in renal tissue. Balb/c male mice of 4–6 weeks old were divided into control and two folic acid treatment groups (Groups A and B). The animals in group A were administered intraperitoneal injection of folic acid (100 mg kg^?1 body weight) for a period of 7 consecutive days while the animal in group B were administered a single intraperitoneal dose of folic acid (250 mg kg^?1 body weight). The renal tissues were collected and used for the analyses of lipid peroxidative indices and activities of antioxidant enzymes in renal tissues. To corroborate biochemical findings scanning electron microscopy (SEM) in renal tissue was studied. Folic acid treated animals demonstrated marked renal hypertrophy accompanied by severe impairment of renal function. Glutathione levels (GSH) and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) levels were significantly decreased and LPO levels increased following FA treatment. SEM results further substantiated the observed biochemical changes as evident by severe inflammation in glomeruli, swelling in primary and secondary pedicels, blebbing in villi, and tremendous deprivation of erythrocytes (RBCs) in FA treated kidneys. The present study therefore suggests that acute administration of folic acid leads to the generation of oxidative stress and altered membrane architecture responsible for folic acid induced ARF.     

Differential expression of androgen and estrogen receptors in PCB (Aroclor 1254)-exposed rat ventral prostate: Impact of alpha-tocopherol

Polychlorinated biphenyls (PCBs) are environmental toxicants, which affect male fertility by altering the androgen and estrogen levels. PCB-induced toxic manifestations are associated with the production of reactive oxygen species. Vitamin E (α-tocopherol) is a major lipophilic chain breaking antioxidant, which protects polyunsaturated fatty acids in tissues against peroxidation, a property that could be beneficial in the male reproductive biology. The purpose of this study was to determine the impact of α-tocopherol on PCB (Aroclor 1254)-induced changes in androgen receptor (AR) and estrogen receptors (ERs) expression in Wistar rat ventral prostate. Rats were divided into 3 groups of 6 animals each. Group I rats were administered corn oil (vehicle) intraperitoneally (i.p.); Group II rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.); Group III rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.) along with simultaneous oral supplementation of 50 mg kg^?1 day^?1 of α-tocopherol. Serum testosterone and estradiol titers were assayed. Prostatic acid phosphatase activity (PAcP), citric acid concentration, generation of hydrogen peroxide (H₂O₂) and lipid peroxides (LPO) were estimated. mRNA and protein expression of AR, ER-α and ER-β in ventral prostate were quantified. Serum testosterone, estradiol, PAcP, citric acid levels, AR and ER-α expressions were significantly decreased while H₂O₂ generation, LPO, ER-β were increased in PCB-exposed animals. Simultaneous supplementation of α-tocopherol in PCB-exposed rats resulted in significant restoration of all the parameters to the control. The results suggest that α-tocopherol has definite protective effect against PCB-induced toxicity in ventral prostatic dysfunction.     

Clinico-hematological and micronuclear changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium

This study was carried out on 90 one-day-old broiler chicks to know clinico-hematological alterations, DNA damage caused by cypermethrin (CY), and attenuation of toxic effects by vitamin E (Vit E) and selenium (Se). Birds were randomly divided into five equal groups. Groups 1–4 received CY (600 ml kg^?1 b.wt) daily for 30 days by crop tubing. In addition to CY, groups 2, 3 and 4 received Vit E (150 mg kg^?1 b.wt), Se (0.25 mg kg^?1 b.wt), and Vit E (150 mg kg^?1 b.wt)+Se (0.25 mg kg^?1 b.wt), respectively. Group 5 served as control. Birds were monitored twice daily for clinical signs. They were weighed and blood samples were collected at experimental days 10, 20 and 30 for hematological studies. CY-treated birds showed more prominent signs of toxicity compared to CY+Vit E, CY+Se and CY+Vit E+Se birds. Body weight in groups 1–3 was significantly (P<0.05) smaller at days 20 and 30 when compared with the control group. Significantly (P<0.001) higher numbers of micronuclei appeared in chicks treated with CY compared to CY+Vit E- and CY+Se-treated birds. Significantly decreased total erythrocyte counts (TEC), hemoglobin (Hb) concentration and packed cell volume (PCV) in all treated groups were recorded. Treated birds suffered from macrocytic hypochromic anemia. Leukocytosis in early stage and later leucopenia was seen in treated birds. It can be concluded that CY induces toxic effects in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective to ameliorate toxic effects of cypermethrin.     

The effect of prolonged oral exposure of cockerels to disinfectant (Iodosteryl®) on induction of oxidative stress and liver damage

This study was designed to investigate the effect of prolonged oral exposure of cockerels to disinfectant (Iodosteryl^®) present in drinking water and its ability to induce liver damage and oxidative stress. Thirty-two healthy birds were used for this study. They were grouped into four groups of eight per group. Group I received 10 ml/kg body weight of physiological saline. Groups II, III and IV received 1 part per million, 2 part per million and 4 part per million of Iodosteryl^® in their drinking water for six weeks. The results revealed significant (P < 0.05) increase in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities in a dose-dependent manner in birds administered with Iodosteryl^® when compared with control. Significant (P < 0.05) increase in sodium and potassium ions was obtained from birds that received Iodosteryl^® (4 part per million) compared with control. Also, there was significant (P < 0.05) increase in total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein levels in all treatment groups (1, 2 and 4 part per million) compared with control. Serum blood urea nitrogen levels increased significantly (P < 0.05) in a dose-dependent manner. Biologic markers of oxidative stress (malondialdehyde and hydrogen peroxide generation) increased significantly with concomitant significant (P < 0.05) decrease in serum glutathione level in a dose-dependent manner when compared with control. Histological sections revealed hepatic congestion, vacuolation and fibrosis at varying concentration of Iodosteryl^®. Overall, Iodosteryl^® induced hepatic damage, increased oxidative stress and decreased antioxidant defense system; hence exposure of both animals and humans to prolonged iodine disinfectant is potentially harmful.     

Protective role of curcumin in nephrotoxic oxidative damage induced by vancomycin in rats

Vancomycin (VAN) is a glycopeptide antibiotic which is active against gram positive bacteria including methicillin resistant Staphylococci. Free radicals are involved in the pathogenesis of vancomycin-induced nephrotoxicity. Therefore, the present study was conducted to investigate the antioxidant potential of curcumin (CUR) against the nephrotoxicity of vancomycin in male rats. Animals used in this study were divided into four groups; the first group was used as control, the second, third and fourth groups were treated orally with curcumin (200 mg/kg BW/day), vancomycin (200 mg/kg BW/day, i.p.), vancomycin plus curcumin, respectively. Curcumin was administered 2 weeks before and 1 week simultaneously with vancomycin. Results showed that thiobarbituric acid reactive substances (TBARS) in plasma and kidney tissue were significantly increased after vancomycin administration. While, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in plasma and kidney tissue and the content of glutathione (GSH) in kidney tissue were decreased compared to control. Vancomycin significantly increased the levels of urea and creatinine. The presence of curcumin with vancomycin caused reduction in induction levels of TBARS in plasma and kidney, urea and creatinine. It ameliorated vancomycin-induced decrease in the activities of antioxidant enzymes and GSH. The presence of curcumin with vancomycin alleviated its nephrotoxic effects. It can be concluded that curcumin has beneficial influences and could be able to antagonize vancomycin nephrotoxicity.     

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4 ± 1.9 mg GAE/g), condensed tannins (58.4 ± 2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe²⁺-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE + Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.     

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 effects of royal jelly on liver damage induced by paracetamol in mice

The present study was undertaken to investigate the protective effect of royal jelly against paracetamol-induced liver damage. The study was conducted in 90 female Swiss Albino mice, and six groups were established. While the first group was maintained as control, Groups 2–6 were administered 200 mg/kg RJ for 1 day, 200 mg/kg RJ for 7 days, 400 mg/kg PAR for 1 day, 200 mg/kg RJ plus 400 mg/kg PAR for 1 day and 200 mg/kg RJ for 7 days and then second 400 mg/kg PAR on the 7th day, orally, respectively. It was shown that PAR significantly increased serum ALT, AST, ALP, liver MDA levels and significantly decreased liver GSH-Px activity, when compared to the control group (Group 1). On the other hand, meaningful changes were observed in the biochemical parameters of the group which was administered long-term RJ (Group 6). The aforementioned parameters which were statistically significant were determined to have drawn closer to values of the control group, and among these, the existing statistical differences for MDA level and GSH-Px activity between the trial group (Group 6) and the control group disappeared (Group 1). Compared to the pathological changes observed in the liver parenchyma, remark cords, sinusoids and hepatocytes in the group which was administered paracetamol alone (Group 4), lesions were determined to be less severe particularly in the group (Group 6) which received royal jelly for 7 days prior to paracetamol. In conclusion, the administration of royal jelly as a hepatoprotective agent for 7 days against paracetamol-induced liver damage was determined to exhibit marked protective effect on liver tissue.     

Possible ameliorative effects of kolaviron against reproductive toxicity in sub-lethally whole body gamma-irradiated rats

Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body γ-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of γ-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to γ-radiation. Gamma-irradiation resulted in a significant (p < 0.05) decrease in body weight and relative testes weight. Also, γ-irradiation significantly (p < 0.05) decreased the activities of superoxide dismutase, catalase and glutathione S-transferase as well as glutathione level, but markedly elevated malondialdehyde levels in the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (p < 0.05) decreased the body weight loss and increased relative testes weights of the rats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together, γ-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity.     

Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver,kidney, pancreas and eye lens in rats

The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg⁻¹ bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug.     

Effect of vitamin C in reducing the toxicity of endosulfan in liver in rabbits

In this study, the effect of endosulfan, an organochlorine pesticide, and the ameliorating effect of vitamin C on the livers of New Zealand white rabbits were studied. Livers of the rabbits were examined grossly and histopathologically, and caspase-3 activity was detected by immunohistochemical methods. A total of twenty-four rabbits were divided into four groups (n=6). Rabbits in Group I (END) were daily given a sublethal dose of endosulfan (1 mg/kg bw) in corn oil by oral gavage for 6 weeks. Group II (END+C) received the same dose of endosulfan and additionally Vit C (20 mg/kg bw) every other day during this period. Group III (OIL+C) received corn oil daily by oral gavage and vitamin C every other day for 6 weeks. Group IV (OIL), the control group, received only corn oil daily, by oral gavage throughout the experiment. The concentration of α-endosulfan in the END group was higher in livers (0.102±0.012 ppb) than the β-endosulfan (0.072±0.001 ppb). Decreased accumulation of α and β endosulfan was observed in the END+C group (0.025±0.003 and 0.016±0.002 ppb, respectively) (p<0.0001). The most prominent gross findings at the necropsy were seen in the END group, in which swollen and pale livers were commonly observed. Hemorrhages, degenerations, necrosis, and in some rabbits bile duct hyperplasia were the marked histopathological findings of the END group. Caspase-3 positive reaction was more severe in this group than in the others. An ameliorating effect of Vit C on gross, histopathological and immunohistochemical findings was observed in the END+C group. The results revealed that endosulfan is highly toxic for rabbit livers. However, toxicity was decreased by Vit C treatment, which reduced the accumulation of endosulfan in livers four-fold.     

Cobalt chloride induces hepatotoxicity in adult rats and their suckling pups

To assess liver damages in pregnant and lactating rats and in their suckling pups, wistar female rats were given through drinking water 350 ppm of CoCl₂ (157 ppm Co²⁺) from the 14th day of pregnancy until day 14 after delivery. The effects of cobalt chloride on lipid peroxidation levels, antioxidant enzyme activities, lipid profile and histopathology aspects of liver were evaluated. Biochemical results showed that lipid peroxidation increased significantly in Co-treated rats, as evidenced by high liver thiobarbituric acid-reactive substance (TBARS) levels. Alteration of the antioxidant system in treated group was confirmed by the significant decline of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content in liver of suckling pups and their mothers. Moreover, CoCl₂ exposure induced an increase in the activities of the aspartate transaminase (AST), alanine transaminase (ALT), lactate deshydrogenase (LDH) and bilirubin levels in pups and their mothers while liver LDH activity and plasma albumin level were significantly decreased. On the other hand, cobalt chloride induced a marked hypoglycemia, a significant decline in triglycerides and total cholesterol levels. Histological studies showed an infiltration of mononuclear cells and vascular congestion in liver of pups and their mothers.Based on the present findings, exposure of rats to CoCl₂ during late pregnancy and early postnatal period affects antioxidant enzyme activities and lipid peroxidation indicating liver damage in mothers and their offspring.     

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.     

The protective effects of vitamin C on the DNA damage,antioxidant defenses and aorta histopathology in chronic hyperhomocysteinemia induced rats

The aim of this study was to investigate the protective effect of vitamin C towards hyperhomocysteinemia (hHcy) induced oxidative DNA damage using the comet assay. The increase in plasma homocysteine levels is an important risk factor for vascular and cardiovascular diseases through free radical production. This study was also conducted to investigate the histopathological changes in the thoracic aorta and the oxidant/antioxidant status in heart, liver and kidney tissues.Twenty-four adult male Wistar rats were divided as control, hHcy and hHcy + vitamin C group. Chronic hHcy was induced by oral administration of l-methionine (1 g/kg/day) for 28 days. Vitamin C was given 150 mg/kg/day within the specified days. DNA damage was measured by use of the comet assay in lymphocytes. Levels of malondialdehyde (MDA) and glutathione (GSH) as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in heart, liver and renal tissues.Results show that l-methionine administration significantly increased % Tail DNA and Mean Tail Moment in hHcy group as compared with other groups. Vitamin C treatment significantly decreased the high MDA levels and increased activity of antioxidant enzymes in tissues. Aortic diameter and thickness of aortic elastic laminae were significantly lower in hHcy + vitamin C group.Comet assay can be used for the assessment of primary DNA damage caused by hHcy. Histopathological findings showed that vitamin C may have a preventive effect in alleviating the negative effects of hHcy. Vitamin C might be useful in the prevention of endothelial dysfunction caused by hHcy.