Mechanistic study on formaldehyde‐induced hepatotoxicity

In isolated, hemoglobin‐free perfused livers of fasted rats, formaldehyde at an initial concentration of 10 mmol/l produced toxicity as evidenced by a release of enzymes (GPT, SDH) and of glutathione (mainly GSSG) into the perfusate, an accumulation of calcium in the liver, and a depletion of hepatic glutathione. Formaldehyde also led to an enhanced release of malondialdehyde into the perfusate, indicating peroxidative processes and decreased hepatic oxygen consumption by about 50–70%. The electron microscopic investigation of formaldehyde‐exposed livers showed a destruction of the mitochondria (ruptured membranes, loss of the cristae) and some damage of the rough endoplasmic reticulum. Feeding the rats prior to surgery attenuated the hepatotoxic effects of 10 mmol/l formaldehyde. At an initial concentration of 3 mmol/l, formaldehyde did not release enzymes from livers of fed or fasted rats but only from those whose glutathione content had been depleted by treatment with phorone (250 mg/kg ip 2 h earlier)...