Protective effect of CO2-induced hyperventilation on the hepatotoxicity elicited by carbon tetrachloride

Abstract

Following oral intake or inhalation, halogenated hydrocarbons are metabolized to hepatotoxic intermediates in the liver to only a small extent, the major part being eliminated via the lungs without biochemical transformation. Following intoxication, increased pulmonary elimination of hydrocarbons can be achieved in patients by treatment with CO2-induced hyperventilation. To investigate the efficacy of this new therapy under exact experimental conditions, female Wistar rats received 2.5 ml CCl4/kg body wt by gastric intubation and were then treated with CO2-induced hyperventilation. In comparison to untreated animals, hyperventilated rats showed only a few signs of hepatic injury by histological evaluation, whereas massive centrilobular necroses and fatty infiltrations were observed in nonhyperventilated animals. By biochemical assessment, significant decreases of GOT [glutamic oxaloacetic transaminase], GPT [glutamic pyruvic transaminase] and GDH [glutamate dehydrogenase] activity were observed in the serum, when hyperventilated rats were compared to untreated animals. The LD50 for CCl4 was almost tripled after hyperventilation compared to nonhyperventilation. The increased LD50 and the biochemical and histological results substantiate the usefulness of CO2-induced hyperventilation therapy in the treatment of intoxications by hydrocarbons under standardized experimental conditions.