Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00–18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00–06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

No abstract

Simultaneous administration of trichloroethylene (TCE), at an oral dose of 0.5 mVkg, resulted in a marked potentiation of liver injury caused by an oral dose of carbon tetrachloride (CCl,, 0.05 mVkg). Hepatic glutathione levels were depressed at 24 hr only in the rats given TCE and CCl,. Using serum enzyme (ALT and SDH) as indicators of hepatotoxicity, potentiation of CCl,-injury was most apparent at 24 hr. Upon histological examination of H&E stained liver sections, the differences between livers obtained from TCE and CC1,-treated rats versus CC1,-treated rats were most apparent at later time points (48 and 72 hr). At 48 hr after CCl,, livers showed a distinctive and uniform pattern of injury with regeneration features predominating over necrosis. At this time, livers from TCE and CC1,-treated rats were characterized by extensive zone 3 coagulative necrosis. Inflammatory infiltrations were less prominent. At 72 hr, morphological features of livers from TCE and CCl, rats were similar to those from ralSgven CCl, alone at 48 hr. From the results obtained, it appears that the regenerative activity of the liver may be delayed in rats simultaneously administered TCE and CCI, as compared to rats administered only CCI,.

No abstract

No abstract