Paracetamol and conventional antimalarial drugs induced hepatotoxicity and its protection by methionine in rats.

Hepatotoxicity, induced in rats, by treatment with high doses of paracetamol and chloroquine was confirmed by estimating blood transaminase levels. Hepatoprotective effect was determined by administering combination of methionine (10% of paracetamol/chloroquine, p.o.) and hepatotoxic drugs quinine. The results were confirmed by histopathological examination of liver. Paracetamol (7 g/kg) and chloroquine (970 mg/kg) administration increased significantly the transaminase levels. Methionine alone did not produced any change. Hepatonecrosis induced by paracetamol, chloroquine alone and their combinations and its protection with methionine was revealed by histopathological study whereas the combination of paracetamol and methionine showed no significant histopathological difference when compared to the normal liver section. The results reveal that, methionine significantly prevented the rise in transaminases levels produced by hepatotoxic doses of paracetamol and chloroquine. But, to prevent occasional cases of paracetamol overdosage, it is not advisable to give methionine concurrently with paracetamol to patients who are taking paracetamol therapeutically.

Investigation of some effects of levamisole on dog blood pressure.

The effects of levamisole were investigated on the blood pressure of anaesthetized dog. Levamisole (0.5 to 4.0 mg/kg) elicited a biphasic effect, an initial brief depressor response followed by a pressor response. The pressor response was dose-related and was blocked by phenoxybenzamine. The residual depressor response was blocked by propranolol. Repeated administration of a high dose of levamisole produced tachyphylaxis. The pressor response to levamisole was not modified by either reserpinization, acute bilateral adrenalectomy or pretreatment with cocaine, whereas pretreatment with dexamethasone, nialamide or pyroaallol shifted the dose-response curve to the right. Levamisole potentiated the pressor responses to noradrenaline, angiotensin and acetylcholine. The effects of levamisole are ascribed to inhibition of monoamine oxidase, catechol-O-methyl transferase, catecholamine uptake2 mechanism and cholinesterase.