Cytotoxic Effect of Fusarium Equiseti Fungus Metabolites Against N-Nitrosodiethylamine- and CCL4-Induced Hepatocarcinogenesis in Rats

Resumo

Fusarium equiseti, an endophytic fungus isolated from the marine alga Padina pavonica, displayed in vitro potent cytotoxicity and selectivity against liver cancer (HEP-G2) cells. This endophyte was therefore submitted to large-scale liquid fermentation to isolate 11 bioactive constituents. The cytotoxic effect of the extract against in vivo hepatocellular carcinoma (HCC) was evaluated in rats with HCC induced by single intraperitoneal injection of N-nitrosodiethylamine (NDEA) followed by subcutaneous injections of CCl₄. After the injection of carcinogen, the fungal extract was orally administered in 25, 50 and 100 mg/kg doses once a day for 10 weeks. The high levels of liver injury and liver cancer markers after NDEA administration were significantly decreased by this treatment with the total fungal metabolites. Histological observations of the liver tissues of rats treated with NDEA and fungal extract co-administered at 100 mg/kg are correlated with the biochemical observations. These findings confirm that F. equiseti total metabolites could restore the activity of hepatic marker enzymes of NDEA-induced hepatocarcinogenesis in rats.