Effect of phenoxy acids on rat liver regeneration.

Phenoxy-acids incorporated in a basal region on a weight basis, were fed to male rats from which two-thirds of the liver had been removed and the extent of regeneration or the liver increment was ascertained over a period of 10 days p.o. Stimulatory responses occurred with the hypolipidemic drugs, ethyl clofibrate, at levels of 0.25% higher or by gavage over the 1st 8 days p.o. at an overall dosage of 1275 mg/kg, 2-(p-chlorophenoxy)propionic acid (0.50, 1.0%), the corresponding o-chloro-acids (0.20 and 0.50%, respectively) and several other with branching of the acid side-chain. The latter included phenoxyisobutyric acid (0.50%), 2-phenoxypropionic acid (1.0%), 2-phenoxybutyric acid (1.0%), the phenoxydimethyl-pentanoic acid, gemfibrozil (0.40%), the herbicide, 2-(2,4,5-trichlorophenoxy)propionic acid (0.10%) and as screened on a few males, possibly, halofenate (0.20%). The liver increments were in the control range for compounds containing straight chain acid substituents as 4-(p-chlorophenoxy)-butyric acid (0.35%), 3-phenoxypropionic acid (0.75%), 3-(p-chlorophenoxy)-1,2-propanediol (0.50%) and phenoxyacetic acid derivatives, including p-chloroacetic acid and the herbicides 2,4-dichlorophenoxy-, 2-methyl-4-chlorophenoxy- and 2,4,5-trichlorophenoxyacetic acids at levels of up to about 0.50%. Where effects resulted with the phenoxyacetic acids, these were in the direction of inhibition of the regenerative process. The response of the female rat to clofibrate either by diet or gavage was rather poor or equivocal but was more definite with 2-(2,4,5-trichlorophenoxy)propionic acid (0.10%). However, intact females were more consistent in eliciting wet and dry liver enlargement with clofibrate (0.25%) as noted earlier by others and with gemfibrizol (0.040%) and the trichlorophenoxypropionic acid (0.10%) but not with 2,4,5-trichlorophenoxyacetic acid at 0.10%.