Cyanide is ubiquitously present in the environment. It is considered as a potent suicidal, homicidal, genocidal and chemical warfare agent. Cyanide toxicity is mediated through inhibition of cellular respiration, but its other complex toxic manifestations are also well documented. There are a number of antidotes available for cyanide poisoning ( e.g. sodium nitrite, 4-dimethyl aminophenol, sodium thiosulphate, etc.), however, there is still uncertainty about their safety, efficacy and correct indication for use. This review provides a comprehensive account of toxicology of cyanide and the present status of various antidotes employed clinically or pursued experimentally.

Objectives: To examine the effects of amiloride on ouabain induced arrhythmias in anaesthetised adult, healthy, guinea-pigs. Methods: In acute studies, amiloride (10 mg/kg) was given intravenously before the onset of constant ouabain (8 (g/100(l/min) infusion, to induce ventricular premature beats (VPB), ventricular tachycardia and /or fibrillation with sudden fall in blood pressure (VT/F) and cardiac arrest (CA). Propranolol (2mg/kg, i.v.) was also studied against ouabain induced arrhythmia as a positive control. Changes in blood pressure (BP) and heart rate (HR) were monitored simultaneously in anaesthetised animals. In chronic studies, amiloride (10 mg/kg) was given intraperitoneally for three days followed by intravenously on fourth day, before ouabain infusion, as described above. Results: In acute as well as in chronic studies, no changes were observed in the quantity of ouabain required to produce arrhythmias after amiloride pretreatment. On the contrary, propranolol increased ouabain requirement very significantly. There were significant changes in BP and HR after amiloride administration in acute studies. In chronic studies also, similar changes were observed in BP and HR after intravenous administration of amiloride. Conclusion: Amiloride in the dosage studied in vivo did not protect the animal from ouabain induced arrhythmias.

Objective: To investigate the effect of probucol on gentamicin-induced nephrotoxicity in rats. Methods: Male Wistar rats were divided into 4 groups; normal saline, gentamicin 80 mg/kg, i.p., intraperitoneally for 8 days, probucol 10 mg/kg, p.o., for 11 days, probucol 3 days and concurrently with gentamicin for 8 days. Blood urea, serum creatinine, plasma malondialdehyde (MDA), creatinine clearance, urinary sodium, potassium and microscopic examination of kidney were performed after the treatment. Results: Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Blood urea and serum creatinine were increased by 963% and 462% respectively with gentamicin compared to saline-treated animals. Co-administration of probucol with gentamicin decreased the rise in blood urea and serum creatinine. Creatinine clearance (Ccr) was significantly decreased by 89% with gentamicin compared to control. Treatment with probucol improved Ccr by 24% compared to gentamicin treated group. There was a 177% rise in lipid peroxidation products (MDA) with gentamicin than control, which was significantly reduced by 44% with probucol. Study of renal morphology by light microscope showed epithelial loss with intense granular degeneration involving >50% renal cortex in gentamicin treated rats, whereas in probucol plus gentamicin treated rat revealed insignificant changes in tubular epithelium. Conclusion: Our data suggest that supplementation of probucol may be useful in reducing gentamicin nephrotoxicity in rats.

Objective: To evaluate the effect of fish oil, on experimental animals exposed to cigarette smoke. Methods: Fish oil was administered orally to male albino rats at a dosage of 0.5 ml/kg b.wt/day to study the effect of fish oil in cigarette smoke exposed animals. During the experimental period ( i.e. 30 or 90 days) the animals were exposed to cigarette smoke for a period of 2 hr/day. At the end of 30 or 90 days the animals were sacrificed, serum was separated and tissues (heart and lungs) were used for the lipid extraction to analyse the biochemical parameters such as total cholesterol, triglycerides, free fatty acids, phospholipids and MDA levels. Results: Animals exposed to cigarette smoke for 30 or 90 days, resulted in the elevated levels of cholesterol and triglycerides in serum and tissues. No significant change was observed in the levels of free fatty acids in both 30 or 90 days of all four groups. The levels of phospholipid was found to be significantly decreased in serum and tissues of the experimental rats after smoke exposure. The above changes were prevented with simultaneous supplementation of fish oil in 30 or 90 days co-treatment. Conclusion: Administration of fish oil may prevent the cigarette smoke induced dyslipidemia in rats.

Objectives: To study the perturbations of calcium homeostasis by methyl isocyanate (MIC), if any. Methods: Hepatic microsomal Ca2+ -ATPase activity, Ca2+ and 45Ca distribution in serum and hepatic subcellular fractions were determined. Results: Addition of MIC in vitro resulted in dose-dependent inhibition of Ca2+ -ATPase. Subcutaneous administration of MIC at lethal dose caused a significant inhibition of Ca2+ -ATPase activity in vivo and significant changes in subcellular Ca 2+ distribution in rat liver as a result of an enhanced extracellular Ca2+ influx. The serum Ca2+ level was decreased. There was an enhanced cytosolic Ca2+ which was accumulated primarily in the mitochondria. In these rats, there was a significant increase in the mitochondrial pool of reduced glutathione (GSH) with a concomitant decrease in the cytosolic GSH. The isolated hepatic mitochondria of these rats showed significantly lower rates of calcium-stimulated respiration. Conclusion: This study suggests that the perturbations in the intracellular calcium homeostasis due to inhibition of Ca2+ -ATPase by MIC in rat liver could be one of the several factors associated with its cytotoxicity.

Objective: The contribution of N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO) to the effect of morphine on hypoxia-induced lethality was investigated in the present experiments. Methods: Mice were subjected to hypoxia by putting them in a tightly closed glass container. The latencies for death were recorded. Results: MK-801 (0.25 mg/kg, i.p.) and N(-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, i.p.), at doses which themselves produced no effect on hypoxia-induced lethality, attenuated the hypoxic effect of morphine (10 mg/kg, i.p.) significantly, but not completely. Concomitant administrations of NMDA (10 mg/ kg) or L-arginine (500 mg/kg, i.p.), completely reversed the protective effects of MK-801 and L-NAME, indicating the possible involvement of NO-linked NMDA receptors in the hypoxic effect of morphine. Conclusion: Hypoxia induced lethality may be, at least partly, mediated through the NMDA-NO pathway.

Objective: To evaluate whether pre-treatment with alpha tocopherol (Vitamin - E) can minimise gastric ulceration induced by pyloric ligation in rats and to delineate the probable mechanism of action. Methods: Alpha tocopherol was administered orally in two different doses for 2 weeks to two groups of 10 rats each, followed by pyloric ligation. After 18 hours, the pH, volume and mucopolysaccharide content of gastric juice and ulcer index were estimated. The results were compared with the control group which did not receive the vitamin, but was subjected to pyloric ligation. Results: Alpha tocopherol administration, in a dose dependent manner, decreased the ulcer index and volume of gastric secretion and increased the mucopolysaccharide content and pH of the juice. Conclusion: Vitamin E protects the gastric mucosa by decreasing gastric acid secretion and increasing the mucus secretion. Its effects may be mediated through its anti-oxidant effect.