Histopathologic and Electron Microscopic Studies on the Acute Toxicity of Ochratoxin A in Rats

Abstract

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.

Ochratoxin A: Comparative pharmacokinetics and toxicological implications (experimental and domestic animals and humans)

“…Similar observations have been made by other authors in rats and mice (Fuchs and Hult 1992, Fuchs et al 1988, Roth et al 1988. The reabsorption of OTA by the kidney has also been proposed to facilitate the residual persistence of the toxin and hence the observed renal toxicity in rodents (Albassam et al 1987, Stein et al 1985. In vivo metabolism of OTA in a number of species including rodents (Størmer et al 1981) and ruminants (Pitout 1969) has been shown to yield predominantly the non-toxic congener ochratoxin-a (OT-a), i.e.…”

Ochratoxin A: The Continuing Enigma

“…58,74,75 The reabsorption of OTA by the kidney has also been proposed to facilitate the residual persistence of the toxin and hence the renal toxicity in rodents. 76,77 In vivo metabolism of OTA in a number of species including rodents 78 and ruminants 79 has been shown to predominantly yield the nontoxic congener ochratoxin-α, that is, the isocumarin moiety lacking the phenylalanine group (Figure 1). This metabolic peptide bond cleavage appears to be a function of the intestinal tract, as little conversion of the parent compound has been observed in either kidney or liver.…”

Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins

“…However, other toxic eOE ects observed include cardiac and hepatic histological abnormalities, aberration of coagulation factors in the rat, accompanied by haemorrhage and thrombosis in the spleen, brain, liver, kidney and heart (Albassam et al 1987), lesions of the gastrointestinal tract and lymphoid tissues in the hamster (Hagelberg et al 1989), myelotoxicity in mice (Boorman et al 1984, MuÈ ller et al 1995, and intestinal fragility and kidney lesions in chickens (Elling et al 1975). Prior et al (1980) noted decreased feed intake in chickens exposed to feed contaminated with 0.5 ppm OTA.…”