Pharmacokinetics Of Methylamine And Its Metabolite Formaldehyde In Animals

Semicarbazide-sensitive amine oxidase ( EC 1.4.3.6; SSAO ) are an group of enzymes containing copper and 6-hydroxydopa quinone, sensitive to inhibition by semicarbazide and other hydrazine compounds. The enzyme can convert primary amines into the corresponding aldehydes, while generating hydrogen peroxide and ammonium at the same time RCH3NH2 + O₂ + H₂O → RCHO + H₂O₂ + NH₃. Methylamine ( MA ) is a endogenous substrate for SSAO and can be deaminated to formaldehyde ( FA), hydrogen peroxide and ammonium. It is abundantly present in urine and also detected in blood and tissues. MA can be derived from several metabolic pathways and ingested from food, drinks and cigarette smoke. FA is extremely reactive and capable of inducing intra- and inter-moleculer cross-linkage between proteins and DNAs. It has been reported that FA produced endogenously via deamination of MA by SSAO. FA can enhance glycosylation of protein and cross-link with protein in vivo, cause endothelial injury and may be a potential risk factor for initiation of atherosclerosis and diabetic complication such as retinopathy. Recently, SSAO has been found to play an important role in glucose uptake and inhibition of lipolysis. And surprisingly, Vascular adhesion protein-1 ( VAP-1 ), an endothelial molecular supporting the adhesence and transmigration of blood-borne lymphocytes to the vascular lining under shear and relating to inflammation, is identified same to SSAO. The enzymatic function of SSAO play a critical role in the physiological function described above and can be completely blocked by specific SSAO inhibitor. Therefore, in the first part of research, we investigated plasma SSAO activity, baseline MA and FA concentration and compared the pharmacokinetics of MA, and its metabolite FA in mice, rats and rabbits, So as to lay a fundation for long-lasting toxicity experiment test and further understand the physiological and pathological significance of plasma SSAO and endogenous FA. In the second part, nitric oxide ( NO ) and glucose concentrations in LPS-induced acute inflammatory rats were monitored in the presense of N'- ( 2-Phenylallyl ) hydrazine hydrochloride...