Selenite-induced protection of bromobenzene hepatotoxicity in male rats

Acute treatment with sodium selenite effectively reduces bromobenzene hepatotoxicity in male, Sprague-Dawley rats. Hepatocellular damage was ameliorated as shown by marked decreases in plasma alanine and aspartate aminotransferase (ALT and AST) activities. A single dose of selenite (12.5 or 30 mumol Se/kg, ip) was administered to rats at 4, 24, 48, or 72 hr before injection of bromobenzene (7.5 mmol/kg, ip). Plasma ALT and AST activities and hepatic glutathione (GSH) content were measured 24 hr after bromobenzene treatment. As the length of time of selenite pretreatment increased, the extent of reduction of bromobenzene-induced elevation in plasma enzyme activities by selenite was enhanced, and generally, in a dose-related manner with optimal protection occurring in rats pretreated 72 hr prior with selenite. However, depletion of liver GSH by bromobenzene was not affected by selenite treatment. Hepatic GSH levels and GSH detoxication enzyme activities were measured at various intervals in rats treated with selenite alone. Selenite increased hepatic GSH content 20 to 25% at both 24 and 48 hr after injection, with a return to GSH control levels at 72 hr. Selenite treatment produced slight decreases in GSH peroxidase activity but did not alter GSH S-transferase activity. These studies suggest that the reduction of bromobenzene hepatotoxicity by selenite does not involve alterations in the activity of hepatic GSH detoxication enzymes; however, the data suggest that factors in addition to selenite-induced changes in hepatic glutathione levels are also involved.