Species difference in intestinal drug metabolising enzymes in mouse, rat and hamster and their inducibility by masheri, a pyrolysed tobacco product.

Activities of several drug metabolising enzymes in the small intestine were investigated in Swiss mice, Sprague Dawley rats and Syrian Golden Hamsters fed 10% masheri, a pyrolysed tobacco product, in diet, for 20 months. The basal levels of enzymes in proximal (PI), medium (MI) and distal (DI) parts of the intestine in the three species were similar. However, the levels of cytochrome P-450, benzo(a) pyrene hydroxylase (B(a)OH) and glutathione S-transferase (GST) were highest in hamsters followed by rat and mice. Upon treatment with masheri, significant induction of cytochrome P-450 and B(a)PH was observed in PI and DI of all the three species. However, GSH and GST was depleted upon masheri treatment in all the three species again only in proximal and distal parts of the intestine. Thus increase in activating enzymes together with depletion in GSH-GST system upon exposure could be an important factor in the susceptibility of the small intestine to hazardous xenobiotic exposure.

Effect of nutritional status on mutagenicity of urine excreted by rats treated with standard/experimental carcinogens.

Urine samples, collected from Sprague Dawley rats treated with extracts of tobacco/masheri, benzo (a) pyrene, N'-nitrosonornicotine, N'-nitrosodiethylamine and maintained on semi-synthetic diets sufficient or deficient in Vitamin A, B and protein were tested for mutagenicity using Salmonella/microsome assay. The mutagenic activity of urine or various treated groups was in the order deficient diet greater than standard laboratory diet greater than nutritionally sufficient diet. Present results confirmed the earlier observations that nutritionally deficient animals are likely to have more exposure to mutagenic metabolites that are generated by increased phase I enzymes and decreased detoxification system.

Effect of masheri, a pyrolysed tobacco product on carcinogen metabolizing enzymes.

Studies on the modulation of the carcinogen metabolizing enzymes on treatment with masheri extract (ME) and benzo (a) pyrene (B (a)P), were carried out in male Sprague Dawley rats (12 weeks old) fed a nutritionally adequate standard diet. Injection (ip) of ME and B (a) P at 3/4 LD50 dose given in 3 doses at 24 hr interval increased the phase I activating enzymes, viz. cytochrome P-450, benzo (a) pyrene hydroxylase and benzphetamine demethylase while both ME and B (a) P significantly depleted glutathione content and decreased glutathione-S transferase activity. Furthermore, the same treatment of ME and B (a) P significantly depleted the hepatic vitamin A pool while a concommittant increase in vitamin C content was observed.