Histopathological studies on the toxicity of ochratoxin A in rats. I. Acute oral toxicity

Masayoshi, Kanisawa; Suzuki, Satoshi; Kozuka, Yoshimichi; Yamazaki, Mikio

doi:10.1016/0041-008x(77)90196-x

Cited by 34 publications

(16 citation statements)

References 20 publications

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“…These observations are in general agreement with those published by other researchers (Kanisawa et al 1977;Galtier etal. 1978Galtier etal.…”

Section: Discussionsupporting

confidence: 95%

“…Studies with rat tissue homogenates have indicated that the duodenum, ileum and pancreas are able to carry out this reaction, whereas the activity in the liver and kidney is low or non-existent in rat hepatocytes (Hansen et al'. 1982) and rabbit and rat liver (Kanisawa et al 1977;Stormer et al 1983). The above authors did not indicate if these tissue preparations were free of microorganisms; if so, they could have significantly contributed the hydrolysis of OA.…”

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confidence: 94%

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Hydrolysis of ochratoxin A by the microbial activity of digesta in the gastrointestinal tract of rats

Madhyastha

Marquardt

Frohlich

1992

Arch. Environ. Contam. Toxicol.

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This study established the influence of dietary neomycin sulphate on the rate of hydrolysis of ochratoxin A (OA) by digesta from the intestine, and its effect on the excretion of OA and its hydrolyzed metabolite, alpha ochratoxin (O alpha), in the urine and feces of the rat. The first in vitro study demonstrated that digesta from the cecum and the large intestine were able to hydrolyze OA whereas digesta from the small intestine and stomach had very low hydrolytic activity against this substrate. Homogenates of the liver had no hydrolytic activity. The second in vivo study demonstrated that digesta from the large intestine and cecum of the neomycin treated rats was much less effective (P < 0.001) in promoting the hydrolysis of OA than digesta from the control rats. Neomycin when added directly to the in vitro system, however, did not affect the rate at which OA was hydrolyzed. In a third study, OA was administered in vivo to control and neomycin-treated rats. Rats fed the neomycin containing diet compared to those fed the control diet had a higher concentration (P < 0.005) of blood OA, and a greater cumulative excretion of OA plus O alpha over the entire 5 day collection period in the feces (P < 0.0001) and a corresponding decrease in the cumulative excretion of OA plus O alpha in the urine (P < 0.0001). Individually, there was a marked increase in cumulative fecal excretion of OA (P < 0.05) and a corresponding decrease in excretion of O alpha (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…These observations are in general agreement with those published by other researchers (Kanisawa et al 1977;Galtier etal. 1978Galtier etal.…”

Section: Discussionsupporting

confidence: 95%

mentioning

confidence: 94%

Hydrolysis of ochratoxin A by the microbial activity of digesta in the gastrointestinal tract of rats

Madhyastha

Marquardt

Frohlich

1992

Arch. Environ. Contam. Toxicol.

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“…On the other hand, it is well known that treatment with 10 mg OTA/kg body mass for 4 days causes glomerular changes and necrosis of epithelial cells of the kidney proximal tubule in rats (Kanisawa et al 1977). For rats, the LD 50 is 22-44 mg OTA/kg body mass.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic effects of OTA in kidneys are usually related to primary lesions of proximal tubules, followed by spontaneous damage of glomeruli and involution of the interstitia (Krogh 1980). In 1977, Kanisawa and colleagues studied acute OTA intoxication, and after several consecutive daily doses produced massive acidophilic degeneration with necrosis and desquamation of epithelium in proximal tubules (Kanisawa et al 1977).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis and oxidative stress induced by ochratoxin A in rat kidney

et al. 2003

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Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of fungi. OTA induces a tubular-interstitial nephropathy in humans and in animals. It has been implicated as one of the aetiological agents involved in the development of endemic nephropathy. OTA-induced oxidative stress and apoptosis may play key roles in the development of chronic tubulointerstitial nephritis connected to the long-term exposure to this food contaminant. We studied the effects of low doses of OTA on kidney cells. Wistar rats were treated with 120 microg OTA/kg bodyweight daily, for 10, 30 or 60 days. Toxin concentration in kidney was proportional to the time of exposure, and amounted to 547.2, 752.5 and 930.3 ng OTA/g kidney tissue after 10, 30 and 60 days, respectively. OTA treatment caused an increased number of cells undergoing apoptosis in both proximal and distal epithelial kidney cells. The apoptotic cells were visualised using the TUNEL assay and staining with haematoxylin and eosin in situ. The number of apoptotic cells in rats treated for 10, 30 and 60 days increased by 5-, 6.4- and 12.7-fold, respectively, compared with the control cells. However, DNA electrophoresis did not show characteristic fragmentation (DNA laddering). The oxidative stress was evident via increased malondialdehyde formation. The concentration of lipid peroxides showed an increase (36%), but the activity of superoxide dismutase decreased (26%) in 60-day treated rats. In spite of the observed biochemical and morphological changes in the kidney cells, renal functional status was preserved to the end of experiment. This study demonstrates that a combination of morphologic and biochemical markers can be used to monitor early cell death in OTA-induced renal injury. We have shown that the exposure to the relatively low OTA concentrations has activated apoptotic processes and oxidative damage in kidney cells.

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“…Acute OTA intoxication after several consecutive daily doses produces massive acidophilic degeneration with necrosis and desquamation of epithelium in proximal tubules (13). In acute toxicity studies, OTA-induced cell death was reported in vivo in rat renal tubules (2).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Effects of Melatonin and Coenzyme Q10 on Oxidative Damage Caused by Single-Dose Ochratoxin A in Rat Kidney

Yenilmez

Işikli²,

Aral³

et al. 2010

Chin. J. Physiol.

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In the study, the effects of relatively high single-dose of Ochratoxin A (OTA) and the antioxidant effects of Melatonin (Mel) and Coenzyme Q 10 (CoQ 10 ) on OTA-induced oxidative damages in rats were investigated. A total of 28 male Sprague-Dawley rats were divided into four groups of 7 rats each: Control, OTA, Mel+OTA and CoQ 10 +OTA groups. Malondialdehyde (MDA) levels in the plasma and glutathione (GSH) levels in whole blood were measured; kidneys (for histological inspection and for apoptosis detection by TUNEL method) and bone marrow samples (for chromosome aberration and mitotic index) were taken. The rats in the OTA group showed limited degeneration of tubular cells. In some tubules karyomegaly, desquamated cells and vacuolization were observed by light microscopy. Mel and CoQ 10 treatment significantly reduced the severity of the lesions. MDA levels of the OTA group were significantly higher than the control, OTA+Mel and OTA+CoQ 10 groups, while GSH levels were significantly lower than the control, OTA+Mel and OTA+CoQ 10 groups. Higher incidences of apoptotic bodies were observed in the kidneys of the OTA group although OTA administration did not significantly change the incidence of apoptotic bodies when compared to the control and antioxidant administrated groups. Although the percentage of the mitotic index was lowest in the OTA group, no statistical difference was found among the groups. Additionally, OTA had no numerical and structural significant effects on chromosomes. It was observed that single-dose OTA administration caused oxidative damages in rat kidney and Mel or CoQ 10 treatment appeared to ameliorate the OTA-induced tissue injuries.

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Histopathological studies on the toxicity of ochratoxin A in rats. I. Acute oral toxicity

Cited by 34 publications

References 20 publications

Hydrolysis of ochratoxin A by the microbial activity of digesta in the gastrointestinal tract of rats

Hydrolysis of ochratoxin A by the microbial activity of digesta in the gastrointestinal tract of rats

Apoptosis and oxidative stress induced by ochratoxin A in rat kidney

Antioxidant Effects of Melatonin and Coenzyme Q10 on Oxidative Damage Caused by Single-Dose Ochratoxin A in Rat Kidney

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