Early hepatic changes induced by nuarimol in rats

It is commonly believed that in short-term tests hepatic cytochrome P-450b inducers stimulate liver enlargement and mitogenesis in the absence of overt hepatotoxic effects. In this investigation male Wistar rats received naurimol (an organochlorine pesticide) in one, three and five oral doses of 31.5, 62.5 and 125 mg kg-body wt. day-, whereupon the effects on liver were determined. The early effects were dose-dependent increases in p-nitroanisole metabolism, hepatocyte proliferation (DNA synthesis and mitotic activity) and liver weight. Five administrations of the lowest does (31.5 mg kg-1 body wt. day-1) did not change liver weight, despite increased p-nitroanisole metabolism and hepatocyte proliferation. In contrast to p-nitroanisole metabolism and hepatomegaly, proliferation was only transient and disappeared even when treatment continued. The increase in binuclear hepatocytes and signs of necrosis suggested that the hepatomitogenic effect of nuarimol reflected a regenerative response, which may simulate the proliferation caused by partial hepatectomy.