de Ferreyra E C, Bernacchi A S, Villarruel M C, de Fenos O M, Castro J A
Centro de Investigaciones Toxicológicas (CEITOX) CITEFA/CONICET, Provincia de Buenos Aires, Argentina.
Exp Mol Pathol. 1993 Jun;58(3):194-204. doi: 10.1006/exmp.1993.1017.
Arsenazo III (AIII) (100 mg/kg ip in saline) administration to Sprague-Dawley male rats 30 min before or 6 or 10 hr after CCl4 [1 ml/kg ip as a 20% (v/v) solution in olive oil] significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as demonstrated either by histology or by determination of isocitric acid dehydrogenase in plasma. AIII did not modify the CCl4 concentrations reaching the liver, the intensity of the covalent binding of CCl4-reactive metabolites to hepatic microsomal lipids, or the CCl4-promoted lipid peroxidation process at either 1 or 3 hr of poisoning. AIII administration enhanced glutathione (GSH) levels in liver and significantly prevented the CCl4-induced minor decreases in GSH content and the CCl4-induced increases in calcium content at 24 hr of intoxication. AIII treatment further enhanced the CCl4-induced decreases in body temperature of the poisoned rats. Results suggest that AIII's preventive effects might be related to its very well-known calcium-chelating properties, but that additional factors related to AIII's ability to increase GSH content in liver or to decrease body temperature of CCl4-intoxicated animals may also play a role.
在给雄性Sprague-Dawley大鼠腹腔注射四氯化碳（CCl4）[以20%（v/v）橄榄油溶液的形式，1 ml/kg腹腔注射]前30分钟，或在注射后6或10小时，腹腔注射（ip）毒胡萝卜素III（AIII）（100 mg/kg，溶于生理盐水中），通过组织学或血浆中异柠檬酸脱氢酶的测定表明，在24小时时，可显著预防肝毒素引起的肝坏死，但不能预防脂肪肝。在中毒1或3小时时，AIII并未改变到达肝脏的CCl4浓度、CCl4反应性代谢产物与肝微粒体脂质的共价结合强度，或CCl4促进的脂质过氧化过程。腹腔注射AIII可提高肝脏中谷胱甘肽（GSH）水平，并在中毒24小时时显著预防CCl4诱导的GSH含量轻微下降以及CCl4诱导的钙含量增加。AIII处理进一步加剧了CCl4诱导的中毒大鼠体温下降。结果表明，AIII的预防作用可能与其广为人知的钙螯合特性有关，但与AIII增加肝脏中GSH含量或降低CCl4中毒动物体温的能力相关的其他因素也可能起作用。
