Methanol induced retinal and hepatic toxicity in the rat model and role of antioxidants

Human methanol poisoning is characterized by serious visual impairment, hepatic toxicity and formic acidemia. Non-primate species are resistant to the accumulation of formate and the associated methanol toxicity. A non-primate model of methanol induced toxicity was developed using adult albino rats treated with subanaesthetic concentrations of nitrous oxide to inhibit the oxidation of methanol's toxic metabolites. Methanol intoxicated rats developed retinal and hcpatic toxicity as well as metabolic acidosis analogous to methanol toxicity in humans. This work was conducted on 140 adult albino rats divided into 5 groups. The first group [control group] was further subdivided into 6 subgroups each consisted of 10 rats. The other 4 groups consisted of 20 rats each. Group Ia was the negative control group, group lb received 2 mL normal saline orally, group Ic was exposed to a mixture of N20: 02 [1:1 flow rate 3 liters/min] for 4 hours, group Id was given methyl alcohol orally in a dose of 4 g/kg followed by further 2 doses [2 g/kg] at 12 and 24 hours after the initial dose, group Ie was given N-acetyl cysteine orally in a dose of 100 mg/kg 30 mill and repeated every 8 hours for further 3 doses, and group If was given melatonin orally in a dose of 30 mg/kg 30 min and repeated every 8 hours for further 3 doses. Group II was exposed to N20: 02 mixture for 4 hours followed by methanol administration orally in a dose of 4 g/kg followed by further 2 doses [2 g/kg] at 12 and 24 hours after the initial dose. Group III was exposed to the mixture of N20: 02 for 4 hours then was given methyl alcohol as in group II then N-acetyl cysteine as mentioned before. Group IV was exposed to the mixture of N20: 02 for 4 hours then was given methyl alcohol as in group 11 then melatonin as mentioned before. Group V was exposed to the mixture of N20: O2 for 4 hours then was given methyl alcohol as in group 11 then N-acetyl cysteine and melatonin together in the same doses and timing as groups III and IV. At the end of the experimental period, the animals were anaesthetized for fundus examination. Then the animals were sacrificed, blood samples were withdrawn for measuring arterial blood gases and malondialdehyde [MDA], the eyeballs and livers were taken for histopathological study. The biochemical results revealed highly significant changes in pH, bicarbonate and malondialdehye concentrations in methanol intoxicated rats [group II]. On administration of N-acetyl cysteine or melatonin after methanol intoxication, there was significant decrease in lipid peroxidation products [MDA] especially with melatonin but the pH changes were not improved. As regard to ocular examination there was a significant improvement in optic disc and retinal edema especially when melatonin and N-acetyl cysteine were given together. Histopathological results of the liver and retina revealed an improvement with either N-acetyl cysteine or melatonin, however, melatonin was more protective. The combination of both antioxidants gave the best results. From the results of this study, It can be concluded that melatonin and/or N-acetyl cysteine have protective effects against methanol-induced ocular and hepatic toxicity

Role of fish oil and vitamin c in protection against nephrotoxicity induced by vancomycin in albino rat

This study aimed to investigate the role of fish oil and vitamin C alone and in combination in renal protection from vancomycin induced nephrotoxicity. Forty adult male albino rats were used in this study and were divided into eight groups of five animals each. The duration of the experiment was ten days, then all the animals were sacrificed and blood samples were collected to investigate the renal functions [blood urea nitrogen and serum creatinine]. Lipid peroxidase activity in both plasma and renal tissue was also estimated. Both kidneys were removed and prepared for histological examination. The results showed that vitamin C induced significant improvement of vancomycin nephrotoxicity. On the other hand, fish oil induced less significant improvement. The maximum protection was observed following combination of both vitamin C and fish oil with vancomycin. This protective effect was obtained both biochemically and histologically

Effect of some vitamins administration on methotrexate-induced damage of rat jejunal mucosa

This work aimed to evaluate the prospective effect of some antioxidants against MTX toxicity. 90 adult albino rats, kept on a standard diet and water, were divided into 5 groups. Group I served as a control group, group II received methotrexate [MTX] in a dose of 2.5 mg/kg b.wt. for 3 consecutive days, group III received MTX concomitantly with vitamin E 600 mg/kg, group IV received MTX concomitantly with vitamin A 5000 IU/kg, and group V received MTX concomitantly with both vitamin E and vitamin A. The results were statistically analyzed and revealed that jejunum of rats with MTX [group I] showed significantly short, wide villi and deep crypts, marked lymphocytic infiltration in epithelium and lamina propria of the villi. Union of the villi either at the bases or their tips was a protective mechanism to decrease the oozing of plasma from the tissue to the lumen. Goblet cells showed decreased intensity of alcian blue stain. Alkaline phosphatase reaction was reduced at the brush border of the villi despite of its increased serum level. The electron microscopic results revealed markedly swollen mitochondria, reduction in the number and size of microvilli at the brush border, the nuclei showed signs of degeneration. Laboratory investigation revealed a significant reduction of TLC, PC, a significant elevation of serum AST, ALT, ALP, urea and creatinine in group II when compared with control group. In the same time, there was significant improvement of the previous parameters in groups III, IV and V when compared with MTX group. Concomitant administration of vitamins E and A with MTX gave the best protection against MTX-induced damage of both intestinal mucosa and laboratory parameters