In vivo depletion of S-adenosyl-L-homocysteine and S-adenosyl-L-methionine in guinea pig lung after chronic S-(-)-nicotine administration.
Guinea pig lung tissue is dramatically depleted of S-adenosyl-L-homocysteine (SAH) after chronic exposure (600 micrograms/h s.c. for 21 days) of animals to either R-(+)- or S-(-)-nicotine enantiomers; S-(-)-nicotine decreased lung SAH levels by 60-fold, while R-(+)-nicotine caused an 11-fold reduction of SAH, relative to control values. Lung S-adenosyl-L-methionine (SAM) levels were also reduced (15-fold and 9-fold reductions with R-(+)- and S-(-)-isomers, respectively) in nicotine-treated animals, compared to controls. These depletions are more pronounced with the S-(-)-enantiomer. Liver tissue levels of SAH and SAM are less affected, in fact, a 4-fold increase in liver SAH levels was observed after exposure of animals to R-(+)-nicotine. These results indicate that chronic exposure to nicotine may perturb important endogenous methyltransferase reactions, which could be a contributory factor in the toxicological effects produced by cigarette smoking.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006710:Homocysteine / Q000031:analogs & derivatives*; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013237:Stereoisomerism
D006710:Homocysteine; D009538:Nicotine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine