Circadian variations in hepatotoxicity of carbon tetrachloride in mice

Male mice of Balb/C strain were administered i.p. carbon tetrachloride, in single doses of 35 and 145 mg/kg, given at variable time of the day. The activity of alanine aminotransferase (ALAT) in serum, and the hepatic level of malondialdehyde (MDA) as well as reduced glutathione (GSH) were adopted as indicators of toxicity. In selected groups, liver histopathology was carried out. The experiment was performed in two series differing in the dynamics of observations. A differentiation of the intensity of toxic effects was found dependent on the time of the day at which animals were administered the xenobiotic. This was especially evident for a lower dose: given in the morning it produced no effects, whereas given in the evening it resulted in distinct elevation of toxicity indicators. Additionally, the correlation was checked between the histopathological evaluation (semiquantitative expression) and serum ALAT activity. A high correlation (r = 0.98) allows for basing the evaluation of liver necrosis on the ALAT activity alone.