Hanzlik R P, Cashman J R
Drug Metab Dispos. 1983 May-Jun;11(3):201-5.
The oxidation of [3H]thiobenzamide (TB) and its S-oxide (TBSO) has been investigated using rat liver microsomes. In the presence of O2 and NADPH, TB is rapidly converted to TBSO plus small amounts of benzamide (BA) by rat liver microsomes; neither benzonitrile nor other metabolites were detected. Under similar conditions, TBSO is converted solely to BA. Studies with metabolic inhibitors and inducing agents indicated that both the S-oxidation of TB and its further conversion to BA, probably via enzymatic oxidation to TBSO2 (a chemically reactive sulfene), are catalyzed mainly by the microsomal FAD-containing monooxygenase. No clear evidence for the involvement of cytochromes P-450 was obtained, but neither could this possibility be excluded. The overall pathway for biotransformation of TB in vitro can be represented as: TB leads to TBSO leads to [TBSO2] leads to BA. The possible role of TBSO and TBSO2 in the in vivo hepatotoxicity of TB and TBSO are discussed in light of their chemical reactivities.
利用大鼠肝微粒体对[3H]硫代苯甲酰胺（TB）及其S-氧化物（TBSO）的氧化作用进行了研究。在氧气和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）存在的情况下，大鼠肝微粒体可迅速将TB转化为TBSO以及少量的苯甲酰胺（BA）；未检测到苯甲腈或其他代谢产物。在类似条件下，TBSO仅转化为BA。使用代谢抑制剂和诱导剂进行的研究表明，TB的S-氧化作用及其进一步转化为BA（可能是通过酶促氧化生成TBSO2（一种化学反应性亚磺烯））主要由微粒体含黄素腺嘌呤二核苷酸（FAD）的单加氧酶催化。未获得细胞色素P-450参与其中的明确证据，但也不能排除这种可能性。TB在体外的生物转化总体途径可表示为：TB生成TBSO生成[TBSO2]生成BA。鉴于TBSO和TBSO2的化学反应性，讨论了它们在TB和TBSO体内肝毒性中的可能作用。
