[Evaluation of the hepatotoxic activity of several chlor-nitro derivatives of benzoic acid]

Hepatotoxic effects of 4-chloro-3-nitrobenzoic acid (x-NBA), 3-nitrobenzoic acid (NBA) and 4-chlorobenzoic acid (CBA) were studied at the doses corresponding to LD50, 1/10 LD50 and 1/50 LD50. The toxic effects were estimated by monitoring alterations in activity of protein-synthesizing system in liver tissue and by the analyses for the presence in blood serum of two tissue-specific cytoplasmic enzymes of liver cells--urokaninase (EC 4.2.1.49) and histidase (EC 4.3.1.3). Single peroral administration of the toxic substances at a dose equal to LD50 led to dissimilar alterations in synthesis of liver proteins: activation within 0.5-5 hrs, distinct increase up to the maximal value within 60 hrs, with a gradual decrease approaching the control values within 8 days. Urokaninase and histidase activities were found in blood serum within 8 hrs after the intoxication, reaching the maximum within 15 hrs and exhibited the constant level during 25 hrs. Then the enzymatic activity was gradually decreased but it did not reach the control values within 70 hrs. After daily peroral administration of these toxic substances at the doses corresponding to 1/10 LD50 and 1/50 LD50, only the first dose inhibited the protein synthesis within 2 weeks. Within this period the enzymes studied were not found in blood serum. Distinct inhibition of the protein synthesis was observed within 4 weeks after administration of both these doses. In this case enzymatic activity was present in blood serum (up to 3 mumole/I L blood serum). Within 2 months after administration of these preparations the alterations studied were the most distinct.