Traiger G J, Gammal L M, Cox D N, Haschek W M
Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence 66045-2500.
Toxicology. 1989 Sep;58(1):43-56. doi: 10.1016/0300-483x(89)90103-0.
Histological examination, plasma urea nitrogen levels (BUN), and renal cortical slice uptake of paminohippurate (PAH) or tetraethylammonium (TEA) were used to assess the nephrotoxicity of thiobenzamide and its para-substituted derivatives in Sprague-Dawley rats. Intraperitoneal injection of p-methylthiobenzamide (PMTB) to rats resulted in dose-dependent nephrotoxicity as judged by increased BUN levels, decreased TEA uptake and histologic examination of the kidney. Para-methoxythiobenzamide and PMTB were more potent nephrotoxins than thiobenzamide, which was itself minimally nephrotoxic. Para-methylthiobenzamide-S-oxide (PMTBSO) was more nephrotoxic than PMTB. Rats were pretreated with 1-methyl-1-phenylbenzoylthiourea (MPBTU), a non-toxic arylthiourea which inhibits the metabolism and toxicity of thiocarbonyl compounds. The nephrotoxicity and hepatotoxicity of PMTB was reduced by treatment with MPBTU 30 min prior to PMTB. Pretreatment with MPBTU protected against the renal toxicity of PMTBSO. The results indicate that electron donating para-substituted thiobenzamides produce dose-dependent renal injury, dependent upon oxidative biotransformation.
采用组织学检查、血浆尿素氮水平（BUN）以及对氨基马尿酸（PAH）或四乙铵（TEA）在肾皮质切片中的摄取情况，来评估硫代苯甲酰胺及其对取代衍生物对Sprague-Dawley大鼠的肾毒性。给大鼠腹腔注射对甲基硫代苯甲酰胺（PMTB），根据BUN水平升高、TEA摄取减少以及肾脏组织学检查判断，可导致剂量依赖性肾毒性。对甲氧基硫代苯甲酰胺和PMTB的肾毒性比硫代苯甲酰胺更强，而硫代苯甲酰胺本身的肾毒性极小。对甲基硫代苯甲酰胺-S-氧化物（PMTBSO）的肾毒性比PMTB更强。用1-甲基-1-苯基苯甲酰基硫脲（MPBTU）对大鼠进行预处理，MPBTU是一种无毒的芳基硫脲，可抑制硫羰基化合物的代谢和毒性。在注射PMTB前30分钟用MPBTU治疗，可降低PMTB的肾毒性和肝毒性。用MPBTU预处理可预防PMTBSO的肾毒性。结果表明，供电子的对取代硫代苯甲酰胺会产生剂量依赖性肾损伤，这取决于氧化生物转化。
