1,3,5-Trinitrobenzene-induced alpha-2u-globulin nephropathy

Male and female Fischer-344 (F-344) and male NCI-Black-Reiter (NBR) rats were dosed with 0, 35.5, or 71 mg 1,3,5-trinitrobenzene (TNB)/kg/day for 10 days. Male F-344 rats were dosed with TNB (0 and 35.5 mg/kg) for 20 and 30 days. Hematoxylin and eosin and Mallory-Heidenhain stains and alpha-2u-globulin and proliferating cell nuclear antigen immunohistochemical stains were performed on kidney sections. All treated male F-344 rats exhibited dose-related accumulation of hyaline droplets containing alpha-2u-globulin in proximal tubules. The kidney weights were significantly increased in male and female rats treated with TNB. Significant increases in cell proliferation in proximal tubules were observed in male F-344 rats. Renal changes observed in TNB-treated rats appeared identical to those from other chemicals that induce alpha-2u-globulin nephropathy in male rats. No hyaline droplet accumulation was found in female F-344 and male NBR rats at any doses. We can conclude that TNB induces dose-related exacerbation of hyaline droplets containing alpha-2u-globulin in male rat kidney and subsequent cell proliferation.