Effect of repeated intraperitoneal exposure to picrotoxin on rat liver lysosomal function.

Effect of repeated (20 days) exposure to picrotoxin (PTX) on rat liver lysosomal function was evaluated by measuring the free and total activities of acid phosphatase, cathepsin D, ribonuclease II (RNAse II) and deoxyribonuclease II (DNAse II). The free activities of the nucleases (both RNAse II and DNAse II) were increased following PTX exposure. The total DNAse II activity was increased by 2.2-fold whereas the total acid phosphatase activity was decreased by 28%. Consequently, the ratios of total activity / free activity were low in the PTX exposed groups, implying loss of membrane integrity. Cathepsin D activity was completely abolished. The results show that repeated exposure to PTX can lead to lysosomal dysfunction in liver.

Dose-related proconvulsant and anticonvulsant activity of isatin, a putative biological factor, in rats.

Isatin (indole-2, 3-dione) is an endogenous compound with anxiogenic properties, which occur within a narrow dose range (15-20 mg/kg, i.p.). Dose increment beyond 50 mg/kg, i.p. leads to the loss of anxiogenesis. Since a link has been postulated between anxiogenic and convulsant activity, the effect of a range of doses of isatin (20-80 mg/kg, i.p.) was investigated on subconvulsant and convulsant doses of two seizure-inducing agents, namely, pentylenetetrazole (PTZ) and 3-mercapto-propionic acid (3MPA) in rats. Isatin was found to induce a dose-related effect on PTZ and 3MPA convulsions. The lower dose (20 mg/kg, i.p.) potentiated PTZ and 3MPA convulsions, a median dose (40 mg/kg, i.p.) had insignificant effect, whereas higher doses (60 and 80 mg/kg, i.p.) of isatin exhibited significant anticonvulsant effect against both PTZ and 3MPA induced clonic convulsions. The investigation, thus, supports the contention that anxiogenic agents increase the susceptibility to chemical seizures. The proconvulsant effect of isatin, may be due to its inhibitory effect on central atrial natriuretic peptide receptors and stimulation of 5-hydroxytryptamine3 (5-HT3) rather than its monoamine oxidase (MAO) B inhibitory action. The anticonvulsant effect on higher doses of isatin, on the contrary, may be induced by its metabolites, including 5-hydroxyisatin.