Hazarika A, Sarkar S N
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243 122, U.P., India.
Toxicology. 2001 Aug 28;165(2-3):87-95. doi: 10.1016/s0300-483x(01)00411-5.
Anilofos and isoproturon are important herbicides of organophosphorus and substituted phenylurea groups, respectively. Isoproturon is an inducer of hepatic drug-metabolizing enzymes. Animals and humans have the potential to be exposed to the mixture of these intentionally introduced environmental xenobiotics, but toxicological interactions between these herbicides are not known. Effects of isoproturon pretreatment (675 mg/kg/day for 3 consecutive days) on the toxic actions of anilofos administered orally as a single dose (850 mg/kg) were evaluated by determining some biochemical attributes in blood (erythrocyte/plasma), brain and liver of rats. Anilofos or isoproturon alone or in combination failed to produce any noticeable signs of cholinergic hyperactivity and behavioural alterations. Isoproturon did not potentiate the anticholinesterase action of anilofos in blood and liver. Inhibition of brain acetylcholinesterase was significantly protected. No significant alteration in anilofos-mediated production of lipid peroxidation was observed in erythrocyte and brain of isoproturon-pretreated rats, but it was significantly increased in liver. Anilofos did not affect GSH and GST. The isoproturon-mediated increase in GSH levels of brain (threefold) and liver (3.6-fold) was also not affected following combined administration. GST activity was increased in liver of rats given isoproturon alone (fourfold) or in combination with anilofos (2.8-fold). Activities of total ATPase, Mg2+-ATPase and Na+-K+-ATPase were not affected in rats given either anilofos alone or herbicides in sequence. With these treatments, there were no alterations in the protein content of plasma, brain and liver. Overall findings of the study indicate that isoproturon pretreatment does not alter the toxicity of anilofos, the GSH-GST metabolic pathway may not have a significant implication in the detoxification of anilofos and the production of a reactive oxygen species may be a factor in mediating anilofos toxicity.
莎稗磷和异丙隆分别是有机磷类和取代苯基脲类的重要除草剂。异丙隆是肝脏药物代谢酶的诱导剂。动物和人类有可能接触到这些有意引入的环境异生物质的混合物，但这些除草剂之间的毒理学相互作用尚不清楚。通过测定大鼠血液（红细胞/血浆）、脑和肝脏中的一些生化指标，评估了异丙隆预处理（连续3天，675毫克/千克/天）对单次口服给予莎稗磷（850毫克/千克）毒性作用的影响。单独或联合使用莎稗磷或异丙隆均未产生任何明显的胆碱能亢进和行为改变迹象。异丙隆并未增强莎稗磷在血液和肝脏中的抗胆碱酯酶作用。脑乙酰胆碱酯酶的抑制得到了显著保护。在经异丙隆预处理的大鼠的红细胞和脑中，未观察到莎稗磷介导的脂质过氧化产生有显著变化，但在肝脏中显著增加。莎稗磷不影响谷胱甘肽（GSH）和谷胱甘肽S-转移酶（GST）。联合给药后，异丙隆介导的脑（三倍）和肝脏（3.6倍）中GSH水平的升高也未受影响。单独给予异丙隆（四倍）或与莎稗磷联合给予（2.8倍）的大鼠肝脏中GST活性增加。单独给予莎稗磷或依次给予除草剂的大鼠中，总ATP酶、Mg2+-ATP酶和Na+-K+-ATP酶的活性均未受影响。经过这些处理，血浆、脑和肝脏的蛋白质含量没有改变。该研究的总体结果表明，异丙隆预处理不会改变莎稗磷的毒性，GSH-GST代谢途径可能对莎稗磷的解毒没有显著影响，活性氧的产生可能是介导莎稗磷毒性的一个因素。
