Renal tubular secretion and reabsorption as factors in ochratoxicosis: effects of probenecid on nephrotoxicity.
Ochratoxin A (OA) is a food-borne fungal metabolite capable of producing nephrotoxicity. Renal clearance of [3H]OA and the effects of probenecid on clearance were compared in sham-operated and partially nephrectomized (surgical removal of 70% of the total renal mass), impaired renal function rats. Sham-operated and partially nephrectomized rats cleared OA at 0.109 and 0.078 ml/min, respectively. These values were significantly lower than glomerular filtration rate (GFR) determined by inulin clearance, indicating net tubular reabsorption. Clearance of a single dose of OA in both sham-operated and partially nephrectomized rats pretreated with probenecid was significantly diminished and provided evidence for the involvement of secretory processes in the elimination of OA. Probenecid (administered before OA or simultaneously with OA) failed to prevent nephrotoxicity in rats exposed to five daily doses of mycotoxin. On the contrary, enhanced nephrotoxicity was exhibited. Decreases in urine osmolality, Na+ and K+ concentrations, and body weight were prominent and, interestingly, renal levels of parent OA were increased (over OA treatment alone) in the presence of probenecid. These data suggest that renal tubular secretion and reabsorption are important factors in modulating the nephrotoxicity of OA and may facilitate the residual persistence of this mycotoxin in the kidneys (via renal recycling). Renal metabolism may contribute to the detoxification of OA.
D000042:Absorption; D000818:Animals; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009793:Ochratoxins / Q000378:metabolism / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D009793:Ochratoxins; C025589:ochratoxin A; D012964:Sodium; D011339:Probenecid; D011188:Potassium