Kupffer cell activation with BCG. Corynebacterium parvum or zymosan protects against acute liver injury induced by carbon tetrachloride in rats.

Kupffer cells have been implicated in the pathogenesis of liver injury, but there is controversy about the effects of activation of these cells on the hepatotoxicity of chemicals and endotoxin. It has been shown that injection of Corynebacterium parvum in rats induces macrophage activation that protects against toxic effects of carbon tetrachloride and acetaminophen, five days after injection, and this protection is due to inhibition of microsomal oxidizing enzymes and increased production of glutathion. To verify if the protective effect occurs soon after Kupffer cell activation, with different activators, male albino rats were treated with intravenous injection of BCG (0.5 ml with 7.5.10(8) bacilli), Corynebacterium parvum (30 mg/kg) or zymosan (7.5.10(6) yeast cells). Fourty-eight hours after the injection of one of the macrophage activators, the animals and rats treated with intravenous injection of saline (controls) received carbon tetrachloride by subcutaneous route (1 ml/kg of CCl4, 3:1 in soybean oil). Fourty-eight hours after the animals were killed after ether anesthesia and fragments of the liver were fixed, paraffin embedded and the sections stained with hematoxylin and eosin. A Weibel grid with 168 points was used to estimate the percent volume of necrosis and severe hydropic degeneration. The results showed that the volume density of necrosis and severe hydropic degeneration were significatively lesser in rats treated with the three Kupffer cells activators. The protection was greater with BCG and Corynebacterium parvum than with zymosan. These results confirm that activation of Kupffer cell with three different activators can induce protection against liver cell injury produced by carbon tetrachloride in rats soon as 48 h after injection of activators.