Effects of 2-chloro-4-acetotoluidine (CAT) toxicity on biochemical and morphological alterations in quail.

Morphological changes in response to 2-chloro-4-acetotoluidine (CAT) toxicity in the quail appeared in the form of progressive necrosis of the kidney, particularly the proximal tubular epithelial cells. Changes at 32 hr after the CAT administration included vacuolar degeneration, dilatation of distal tubules containing hyaline and granular casts, overt necrosis, and deposition of urate casts in collecting tubules. There were no striking histopathological changes in the liver at 24 hr. However, small focal necrotic lesions were seen 32 hr after the CAT administration. A 40% protection against the toxicity of CAT at the lower dose was seen in quail pretreated with phenobarbital. The protection offered by phenobarbital pretreatment was attributed to a quantitative shunting of CAT and/or its reactive metabolite along the microsomal-mediated metabolic pathway of the kidney responsible for their inactivation. Administration of reduced glutathione (GSH) to quail treated with CAT offered little protection against the toxicity. The quail treated with a toxic dose of CAT had an increased level of thiobarbituric acid (TBA) reacting products in the liver, with a concomitant decrease in GSH content. This suggests that lipid peroxidation may be involved in CAT-induced hepatic damage of quail. It was hypothesized that the depletion of protective GSH stores coincident with gradual shutdown of the protective peroxidase system of the kidney may occur in a more advanced stage of CAT toxicity in quail. This would then result in a severe disturbance in renal excretion of uric acid and in frank necrosis of renal tubules.