Ochratoxin A was given by gavage to male rats. Moribund and dead animals were necropsied, and the surviving rats, including the controls, were killed 48 hours after dosing. Many of the principal rats were moribund, or began dying, within 12 to 24 hours after dosing. Lesions suggestive of disseminated intravascular coagulation were seen by light microscopy as early as 12 hours after dosing; fibrin deposits were in the spleen, brain choroid plexus, glomerular capillaries, liver, and heart. Renal tubular nephrosis, hepatic and lymphoid necrosis, and necrotic enteritis with villous atrophy were also seen. Electron microscopy demonstrated fibrin strands mixed with degranulated platelets, necrotic leukocytes, and swollen endothelial cells in glomerular capillaries. Myocardial changes included focal supercontracted sarcomeres adjacent to intercalated disks. Swollen sarcolemma, lysed myofibrils and fragmented Z-bands with interstitial edema, vascular thrombosis, and endothelial damage were also seen. The acute pathologic changes induced by ochratoxin A in the intestine, liver, and lymphoid tissues were more obvious than the tubular nephrosis, and the development of a disseminated intravascular coagulation-like syndrome with myocardial changes was a complicating factor.
The protective effect of sodium bicarbonate (NaHCO3), a urine modifier, to alleviate murine ochratoxicosis was investigated. The study included two trials. Urinary pH was altered before oral administration of ochratoxin A (OA) in Trial 1, and animals were given combined doses of OA and ethyl biscoumacetate (Eb) in Trial 2. Acute toxicity of OA as measured by LD50 values was reduced by 23% and 20% in rats treated with NaHCO3 for Trials 1 and 2 respectively. Bicarbonate-treated rats dosed with 20 mg/kg OA or with a combination dose of OA at 17 mg/kg and Eb at 50 mg/kg, had a lower frequency of histological lesions in kidneys, liver, lung, spleen and heart. Two types of heart lesions found in the present study are described.
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