Experimental verification of the possibility of in vivo formation of nitrosocompounds upon combined action of dodecylguanidineacetate and sodium nitrite.
The pollution of the environment with pesticides of different chemical classes (amines, carbamates, guanidines, etc.) and nitrogen fertilizers creates the danger of the in vivo formation of carcinogenic nitrosocompounds. The fungicide Dodin represents dodecylguanidineacetate (DGA), whose chemical structure presupposes a possibility for nitrosofication in the presence of nitrites. The experiments were carried out on albino rats in which 1/10 LD50 sodium nitrite and DGA were introduced orally and in combination. On the 1st, 2nd, 4th, 8th, 15th and 30th days after the onset of the effect we determined the activity of the oxidases with mixed function (OMF) at two levels of biological organization: at the level of intact organism after loading with aminopyrine (AP) and subsequent determination of its basic metabolites in the urine; at subcellular level (microsomal liver fraction) - by the velocity of N-demethylation of AP, hydroxylation of aniline and by the cytochrome P-450 content. The independent action of sodium nitrite leads to a slight inhibition of OMF at subcellular level (28--34%) only after a single treatment. DGA does not change the activity of OMF. The combined action of the two agents causes considerable OMF inhibition (63--67 per cent) on the 1st, 2nd, 4th and 15th days at both levels. The concentration of microsomal protein decreases parallel to OMF inhibition. The data obtained suggest that a new compound is formed under the conditions of the experiment, probably through in vivo nitrosification of the pesticide. This is also testified by the established qualitatively different effect of the preliminary induction of OMF with phenobarbital on the acute toxicity of the noxae studied: lack of effect for DGA, increase for sodium nitrite and decrease for their combination.
D000818:Animals; D001711:Biotransformation; D004790:Enzyme Induction / Q000187:drug effects; D006146:Guanidines / Q000378:metabolism* / Q000494:pharmacology; D007928:Lethal Dose 50; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012977:Sodium Nitrite / Q000378:metabolism* / Q000494:pharmacology
D006146:Guanidines; D009573:Nitrites; D009603:Nitroso Compounds; C006921:dodine; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D012977:Sodium Nitrite; D010634:Phenobarbital