tetraphenylporphine and Chemical-and-Drug-Induced-Liver-Injury

Three structurally similar tetraphenylporphyrins bearing polyhedral borane anions have been synthesized and their toxicological profiles obtained in rats. These conjugates were found to have quite different acute toxicities as manifested at the maximum tolerated dose (MTD). When given at the MTD and observed over 28 days, the most acutely toxic porphyrin was found to be devoid of toxicity, as measured by blood chemistry panels. The remaining two less acutely toxic compounds both elicited significant changes, characterized by moderate to severe thrombocytopenia, failure to gain weight normally and changes in liver enzymes indicative of mild hepatotoxicity. All toxic effects were transient, with platelets rebounding to above normal levels at day 28. We conclude that thrombocytopenia is the dose limiting toxicity for boronated porphyrins in mammals and suggest that these effects may be due to the porphyrin, not the borane or carborane.

Topics: Animals; Anions; Boranes; Chemical and Drug Induced Liver Injury; Heart Diseases; Hemorrhage; Kidney Diseases; Liver; Lung Diseases; Male; Maximum Tolerated Dose; Necrosis; Porphyrins; Rats; Rats, Inbred F344; Thrombocytopenia; Weight Gain