AF Stein; S Gerrling; HH Mollenhauer; ND Heidelbaugh; TD Phillips
Type of Document:
Journal of Toxicology and Environmental Health
Date of Publication:
Place of Publication:
Abstract: The effects of ochratoxin A (OA), a nephrotoxic mycotoxin, were investigated in partially nephrectomized (PN) rats (approximately 70% reduction in renal mass) following compensatory hypertrophy of the renal remnant. Renal function stabilized 27 d after surgery. PN rats compensated for the initial loss of renal function except for glomerular filtration rate (GFR, inulin clearance); this remained significantly impaired. Sham-operated (SO) rats cleared inulin and p-aminohippurate (PAH) at rates of 3.84 and 7.49 ml/min, respectively, while compensated PN rats cleared inulin at 2.51 and PAH at 8.84 ml/min. Daily administration of low levels of OA produced decreased urine osmolality and body weight with a modest increase in urinary protein of PN versus SO rats. OA-treated rats cleared inulin, creatinine, and PAH at rates significantly lower than nontreated controls: 0.89 and 1.96 ml/min for inulin, 0.35 and 0.56 ml/min for creatinine, and 2.29 and 6.23 ml/min for PAH. Histopathological findings indicated a considerable increase in renal tubular necrosis and subcellular damage (i.e., loss of cytoplasmic ground substance, vacuolization, degeneration of mitochondria, and reorganization of endoplasmic reticulum) in PN animals versus controls, concurrent with alteration in renal function. These results verify that the nephrotoxic action of OA is elicited mainly in renal proximal tubules and is enhanced in the PN rat.