Some outcomes and a hypothetical mechanism of combined lead and benzo(a)pyrene intoxication, and its alleviation with a complex of bioprotectors

Abstract

Rats were exposed 3 times a week during 6 weeks to repeated intraperitoneal injections of lead acetate solution in water (Pb) and/or benzo(а)pyrene solution in petrolatum oil (B(а)P) in various dose ratios. Towards the end of the period, the animals developed a moderate subchronic intoxication having some features characteristic of lead effects. The type of combined toxicity estimated with the help of isoboles constructed by the Response Surface Methodology was found to be varied depending on a particular effect, its level, and dose ratio. However, Pb and B(a)P in combination often displayed an additive or even superadditive action. In the group exposed to this combination compared with the group of rats exposed to B(a)P alone, its concentration in the organism was increased while the concentration of some B(a)P oxidative metabolism products was reduced. Such inhibition of B(a)P biotransformation, assumingly associated with impaired heme and, thus, cytochrome P450 synthesis induced by lead intoxication, can serve as an explanation for certain enhancement of the genotoxic effect of B(a)P. This effect was not present in the same combined intoxication if a complex of antitoxic bioprotectors was being administered in the background.