title: 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.
authors.affiliation: a Faculty of Pharmaceutical Sciences , Chiba University , Chiba , Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koizumi
authors.affiliation: a Faculty of Pharmaceutical Sciences , Chiba University , Chiba , Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tajima
authors.affiliation: a Faculty of Pharmaceutical Sciences , Chiba University , Chiba , Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hara
authors.affiliation: a Faculty of Pharmaceutical Sciences , Chiba University , Chiba , Japan.
authors.forename: N
authors.initials: N
authors.lastname: Emi
authors.affiliation: b Hospital Pharmacy, Chiba University , Chiba , Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohmori
authors.affiliation: c Radioisotope Research Center , Chiba University , Chiba , Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kumagai
authors.affiliation: d Faculty of Engineering , Chiba University , Chiba , Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tatsumoto
authors.affiliation: a Faculty of Pharmaceutical Sciences , Chiba University , Chiba , Japan.
authors.forename: K T
authors.initials: KT
authors.lastname: Suzuki