Miranda C L, Henderson M C, Reed R L, Schmitz J A, Buhler D R
J Toxicol Environ Health. 1982 Mar;9(3):359-66. doi: 10.1080/15287398209530169.
The influence of Zn on the acute hepatotoxicity of pyrrolizidine alkaloids (PAs) was determined in male rats. Zinc, 72 mumol/kg as ZnCl2, was administered ip for 3 consecutive days, followed 16 h after the last dose by a single ip injection of purified mixed PAs (80, 120, or 160 mg/kg) obtained from tansy ragwort (Senecio jacobaea). Hepatotoxicity of the PAs was assessed by measuring the activities of plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) and by histological examination of the liver. There was a dose-dependent increase in plasma GOT and GTP 24 h after PA administration, whereas no significant increase of these enzymes was seen after administering Zn alone. The 7-fold increase in plasma GOT and 12-fold increase in GPT after PA (120 mg/kg) were reduced to 2.4- and 2.1-fold, respectively, by Zn pretreatment. The PA-induced liver necrosis was either reduced in severity or abolished by Zn when the PA dose was 80 or 120 mg/kg. These results suggest a protective effect of Zn against PA hepatotoxicity. The protective effect was associated with a marked increase in liver metallothionein and a significant decrease in hepatic cytochrome P-450 content, aminopyrine N-demethylase activity, and in vitro microsomal conversion of the PAs to pyrroles. Liver nonprotein sulfhydryls were unchanged. The possible role of metallothionein in the sequestration of pyrrole metabolites merits further investigation.
在雄性大鼠中测定了锌对吡咯里西啶生物碱（PAs）急性肝毒性的影响。以氯化锌形式给予72 μmol/kg的锌，腹腔注射，连续3天，在最后一剂后16小时，腹腔注射一次从千里光（Senecio jacobaea）中获得的纯化混合PAs（80、120或160 mg/kg）。通过测量血浆谷氨酸草酰乙酸转氨酶（GOT）和谷氨酸丙酮酸转氨酶（GPT）的活性以及肝脏组织学检查来评估PAs的肝毒性。给予PAs后24小时，血浆GOT和GTP呈剂量依赖性增加，而单独给予锌后未见这些酶显著增加。锌预处理后，PA（120 mg/kg）给药后血浆GOT的7倍增加和GPT的12倍增加分别降至2.4倍和2.1倍。当PA剂量为80或120 mg/kg时，PA诱导的肝坏死严重程度降低或消失。这些结果表明锌对PA肝毒性有保护作用。这种保护作用与肝脏金属硫蛋白显著增加以及肝细胞色素P-450含量、氨基比林N-脱甲基酶活性和PAs在体外微粒体中向吡咯的转化显著降低有关。肝脏非蛋白巯基未改变。金属硫蛋白在螯合吡咯代谢产物中的可能作用值得进一步研究。
