Suppressive effect of molybdenum on hepatotoxicity of N-nitrosodiethylamine in rats

Abstract

In order to elucidate the preventive mechanism of molybdenum (Mo) against carcinogenesis of N-nitroso compounds, the effects of in vivo Mo-pretreatment on N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in rats were examined. Effects of in vitro Mo-pretreatment on NDEA-induced DNA strand breaks and fluctuation of the cytosolic free Ca levels in rat hepatocytes were also investigated. Male Wistar rats weighing 170-190 g were pretreated with 10 ppm Mo as Na2MoO4 in deionized drinking water for 21 days, and on day 22, they were exposed to NDEA (50 mg/kg body weight, once, i.p.). 3 and 5 days after NDEA exposure, serum lactic dehydrogenase (LDH) activity, and hepatic calcium (Ca) content and lipid peroxidation levels were evaluated. In vivo Mo-pretreatment prevented NDEA-induced elevations in serum LDH activity and liver Ca content but increased hepatic lipid peroxidation levels. Hepatocytes isolated from rats pretreated with sodium phenobarbital (80 mg/kg body weight, i.p., once a day for 3 days) were exposed to NDEA (0, 100, 250 and 500 μM) in vitro for 30 min at 37°C. NDEA treatment caused DNA strand breaks and a perturbation of cytosolic free Ca level. However, in vitro Mo-pretreatment (20 μM, 20 min at 37°C) suppressed the NDEA-induced DNA damage and disruption of intracellular Ca homeostasis. These results suggest Mo protected against NDEA-induced hepatotoxicity by stimulating the metabolism of the nitroso compound via a nontoxic pathway (denitration) while preventing DNA damage connected with alteration in cytosolic free Ca levels. Thus, the general protective action of Mo against N-nitroso compound-induced carcinogenesis may be explained by a common mechanism.

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats

“…Hepatic injury elicits intracellular stress that leads to peroxidation of membrane lipids accompanied by alteration of structural and functional characteristics of the membrane, resulting in the altered functions of these enzymes. A similar observation showing disruption in calcium and potassium metabolism possibly due to the damage to transport pumps in the livers of DEN treated rats was reported by Koizumi et al (1995). The reversal in the levels of membrane bound ATPases during treatment with ELE indicates that it is highly effective in maintaining membrane integrity, thereby preventing hepatocellular membrane damage.…”