CITRININ MYCOTOXICOSIS IN THE RABBIT (NEPHROTOXICITY)
Abstract
Studies were done to characterize the clinical, pathological and clinicopathological features of citrinin mycotoxicosis in the rabbit. For administration citrinin was dissolved in 0.5 N NaOH and adjuted to neutral pH with HCl. The single-dose 72-hour LD(,50) was 50 mg/kg after intraperitoneal and 134 mg/kg after oral administration. Alterations were confined to the kidneys, consisting of degeneration and necrosis of proximal convoluted tubules and straight segments. After a single oral dose of 130 mg/kg, the earliest lesion was cytoplasmic vacuolation of tubular cells. Seven days after a single oral dose of 120 mg/kg, renal alterations were regeneration of tubular epithelium and slight tubular cell necrosis. Rabbits given 7 daily oral doses of 33.5 or 77 mg/kg had mild tubular degeneration and necrosis and tubular regeneration. The clinicopathologic alterations during 24 hours after a single oral dose of 120 mg/kg were studied. Azotemia and metabolic acidosis with hemoconcentration and hypokalemia developed within 4-12 hours. Clinicopathologic parameters and urinalysis were evaluated for 7 days after a single oral dose of 80 or 100 mg/kg. Increased BUN and creatinine values and decreased creatinine clearance indicated renal failure and urinalysis findings of glucosuria, isosthenuria and cylindruria indicated tubular dysfunction and necrosis. Alterations were most severe on days 2-4, returning to near normal by day 7. Ultrastructural alterations within 12 hours after a single oral dose of 120 or 67 mg/kg citrinin were studied. In S(,2) and S(,3) segments of the proximal tubules, alterations included brush border disruption, cytoplasmic rarefaction and swelling of interdigitating processes. At the higher dose, mitochondria appeared condensed and distorted. Medullary and cortical straight distal tubules had marked distention of the intercellular spaces and disorganization of interdigitating processes. In the cortical and outer medullary collecting ducts the changes were milder. Alterations were suggestive of damage to membrane structure and/or function and interference with cellular bioenergetics. Leukocytic infiltration indicated a contribution of inflammation to development of the lesions.
Degree
Ph.D.
Subject Area
Veterinary services
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