Effect of Antihistamines on Mitochondrial Swelling and Liver Injury

Abstract

Gallagher, Gupta, Judah and Rees¹ showed that thioacetamide, a liver carcinogen, would cause liver necrosis in rats and that a variety of antihistamines would afford protection. It was concluded that thioacetamide acted at the cell surface, but its mode of action was obscure, especially as no in vitro effect could be obtained. It has now proved possible to show an in vitro action of this compound. Liver slices, cut in the conventional manner from the livers of normal rats of the Wistar strain, show a gradual loss of certain dehydrogenases when suspended in saline solutions. Thioacetamide greatly increases this loss. Malic dehydrogenase was chosen as a suitable test system. The loss of this enzyme is shown in Table 1, which illustrates a typical experiment in the untreated slice. The effect of thioacetamide at a concentration of 0.02 M is shown and it can also be shown at concentrations of 5×10⁻³ M. These concentrations are in reasonable accord with the doses employed by Gallagher et al. ¹, that is, 200 mgm./kgm., when it is remembered that extracellular water is of the order of 16 per cent and assuming uniform distribution of the drug.