Effect ofIn Vivo andIn Vitro treatment with arsenite on rat hepatic mitochondrial and microsomal enzymes

Abstract

The effects of arsenite on activities of several enzymes including mitochondrial pyruvate dehydrogenase (PDH) and succinate dehydrogenase (SDH), microsomal cytochrome P450 and b5, NAD(P)H cytochrome C reductase and glutathione S-transferase were studied. The effects of arsenite on the mitochondrial membrane lipid peroxidation (LPO), the content of hepatic cytosol reduced glutathione and the activity of glutathione peroxidase was also investigated in rats. The results indicated that the activities of mitochondrial PDH and SDH were inhibited to 59 % and 57 % of the control activities respectively after arsenite was administered by intraperitoneal injection (i. p.) for 7 consecutive days at a dose of 20 mg/kg. Administration of arsenite led to a potential decrease of GSH content. The increase in lipid peroxidation of liver mitochondrial membrane prepared from rats treated with arsenite was also observed (P<0. 05). Arsenite did not appear to affect the liver cytosolic glutathione peroxidase and microsomal enzyme activitiesin vivo. Inin vitro test, liver mitochondria and cytosol were treated with arsenite, which led to a decreased SDH activity and GSH content and increase of mitochondrial LPO in a dose-dependent pattern that was similar to the results obtained inin vitro experiments. Selenite played a significant antagonistic role in effects of arsenite eitherin vivo orin vitro on the activities of mitochondrial PDH and SDH, and the content of mitochondrial LPO and cytosolic GSH. This results suggested that the toxic effects of arsenite on rat were associated with increased levels of LPO and the injured SH group in body caused by arsenite.

Keywords

arsenite / mitochondria / microsome / glutathione / lipid peroxidation / glutathione peroxidase