Action of drugs and chemical agents on rat liver regeneration.

Chemical agents and drugs of widely differing pharmacological activity have been administered to partially hepatectomized male rats and the extent of liver regeneration ascertained over a period of 10 days. Of the large number investigated, the following fed ad lib in diets supplemented in a basal ration at the weight percentages indicated, proved to be hepatotrophic: anticonvulsants - mephenytoin (0.15), methsuximide (0.15), phensuximide (0.15) and primidone (0.10); benzodiazepines - clobazam (0.10), flurazepam hydrochloride (0.12), halazepam (0.070), oxazepam (0.030) and temazepam (0.10); anti-inflammatory agents - benoxaprofen (0.040), ibuprofen (0.10 and 0.20), naproxen (0.040) and sulindac (0.075); sedatives and hypnotics - ethinamate (0.75), glutethimide (0.075), methaqualone (0.030 and 0.10) and methprylon (0.30) and the analgesic and antipyretic, aminopyrine (0.15); antifungal - griseofulvin (0.50); anti-androgen - cyproterone acetate (0.020 and 0.050); uricosuric - sulfinpyrazone (0.050 and 0.20); skeletal muscle relaxant - chlorzoxazone (0.20); hydrocholeretic - florantyrone (0.30); anti-hypertensive - prazosin hydrochloride (0.010) and the thyroid inhibitor, methimazole (0.025). The feeding of several of the stimulants at the given levels to intact males elicited wet and dry liver enlargement. Most of the current test agents as screened in operated rats, had little effect on the regeneration and in fact, tended to depress the process when higher levels were fed or injected.