Lipid peroxidation in rat liver microsomes: influence of carcinogenic N-nitrosocarbaryl.
The reactivities of carbaryl, N-methyl 1-naphthylcarbamate insecticide and its N-nitrosated derivative carcinogenic, N-nitrosocarbaryl, were investigated on the microsomal hepatic lipid peroxidation and NADPH-dependent reductase activities. The in vivo treatment by N-nitrosocarbaryl produced a reduction in lipoperoxidative degradation induced in vitro by NADPH with regard to the formation of malonaldehyde and conjugated dienes. Carbaryl, its precursor did not affect lipid peroxidation under the same in vivo conditions. Moreover, following administration of the 2 compounds, the activities of NADPH-cytochrome c reductase as well as NADPH-neotetrazolium reductase were significantly decreased by N-nitrosocarbaryl but not influenced by carbaryl. Correspondingly, in vitro studies were performed; different action patterns of the 2 tested xenobiotics were also noted after treatment of rat liver microsomes in vitro by carbaryl and N-nitrosocarbaryl especially in their ability to cope with microsomal oxygen activation. N-Nitrosocarbaryl proved to have a potent inhibitor concentration effect on NADPH-dependent chemiluminescence response in vitro; carbaryl was virtually ineffective on this parameter. No significant difference appeared in the affinity of N-nitrosocarbaryl and carbaryl for the microsomal phospholipids. From the in vitro explorations, it was suggested that carcinogenic N-nitrosocarbaryl may be involved in the inhibition mechanism of microsomal lipid peroxidation through decreases in both NADPH-dependent reductase activities and superoxide generation.
Beraud
M
M
Institut National de la Santé et de la Recherche Médicale, Unité 87, Groupe de Recherches sur la Toxicologie des Aliments et des Boissons, Toulouse, France.
Forgue
M F
MF
Pipy
B
B
Didier
A
A
Carre
P
P
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D012721:Carbaryl / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects*; D008163:Luminescent Measurements; D008862:Microsomes, Liver / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000477:Alkylating Agents; D002273:Carcinogens; D009602:Nitrosamines; D010743:Phospholipids; C008649:nitrosocarbaryl; C021848:NADPH-tetrazolium reductase; D009251:NADPH-Ferrihemoprotein Reductase; D012721:Carbaryl