Studies on hydrazine hepatotoxicity. 1. Pathological findings.

The pathogenesis and factors affecting hydrazine-induced fatty liver have been investigated in rats using histological and ultrastructural examination. A dose of 20 mg hydrazine/kg caused the accumulation of lipid, swelling of mitochondria, and the appearance of microbodies in both periportal and midzonal hepatocytes and in the proximal tubular cells of the kidney. These changes were detectable by light or electron microscopy 24 h after dosing with hydrazine. A dose of 60 mg/kg was the highest dose tolerated for 24 h, but the severity of the fatty liver was similar to that after a dose of 40 mg/kg. The accumulation of lipid droplets and the swelling of mitochondria were detectable by electron microscopy 30 min after dosing, but the accumulation of fat could not be detected by light microscopy until 4 h after dosing. Pretreatment of animals with phenobarbital or piperonyl butoxide respectively reduced and increased the severity of the fatty liver. Pyruvate azine was much less toxic than the parent hydrazine on a molar basis, although some fatty vacuolation was detectable in midzonal hepatocytes.