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[赭曲霉毒素诱导的实验性和人类肾毒性]

[Experimental and human nephrotoxicity induced by ochratoxins].

作者信息

Fillastre J P

机构信息

CHU de Rouen.

出版信息

Bull Acad Natl Med. 1997 Oct;181(7):1447-60; discussion 1460-3.

PMID:9528187
Abstract

Ochratoxin A is a mycotoxin: a dihydroisocoumarin derivative linked to L. beta phenylalanine. Ochratoxin A is produced by a number of Aspergillus and Penicillium species. This mycotoxin is a carcinogenic, teratogenic, mutagenic and immunosuppressive substance. Ochratoxin A is a common contaminant found in a variety of foods for human nutrition as well as animal feeds. The aim of this study is to discuss nephrotoxic properties of this mycotoxin in humans. Nephrotoxicity has been reported in many animals after exposure to ochratoxin A. Porcine nephropathy due to this mycotoxin is a well known disease characterized by impairment of proximal renal function. Renal damage is also confined to the proximal tubule in other animal species. A good correlation is found between renal function abnormalities and the location of the lesions along the nephron. Of particular interest is the presence of nuclear abnormalities of the epithelial cells with pyknosis, karyorrhexis and karyomegaly. The question is to know if ochratoxin is nephrotoxic in humans. Acute nephrotoxicity seems to be very rare and we found only one case report suggesting such a possibility. We observed the occurrence of chronic renal failure in two patients with a possible responsibility of a chronic ochratoxin A intoxication. Clinical and histologic findings in these two patients were quite similar to those described in several cases of karyomegalic interstitial nephritis. Striking similarities between the changes in renal structure and function seen in ochratoxin A-induced experimental nephropathies and in Balkan endemic nephropathy suggest a common etiologic agent. This mycotoxin could be also responsible for interstitial nephropathies in North Africa.

摘要

赭曲霉毒素A是一种霉菌毒素:一种与L-β-苯丙氨酸相连的二氢异香豆素衍生物。赭曲霉毒素A由多种曲霉属和青霉属菌种产生。这种霉菌毒素是一种致癌、致畸、致突变和免疫抑制物质。赭曲霉毒素A是在各种人类营养食品以及动物饲料中常见的污染物。本研究的目的是探讨这种霉菌毒素对人类的肾毒性特性。许多动物在接触赭曲霉毒素A后都有肾毒性的报道。由这种霉菌毒素引起的猪肾病是一种众所周知的疾病,其特征是近端肾功能受损。在其他动物物种中,肾脏损伤也局限于近端小管。肾功能异常与沿肾单位病变的位置之间存在良好的相关性。特别值得关注的是上皮细胞核异常的存在,表现为核固缩、核碎裂和核肿大。问题是要了解赭曲霉毒素对人类是否具有肾毒性。急性肾毒性似乎非常罕见,我们仅发现一例病例报告提示有这种可能性。我们观察到两名患者发生慢性肾衰竭,可能与慢性赭曲霉毒素A中毒有关。这两名患者的临床和组织学表现与几例核肿大性间质性肾炎所描述的表现非常相似。在赭曲霉毒素A诱导的实验性肾病和巴尔干地方性肾病中,肾脏结构和功能变化之间的显著相似性表明存在共同的病因。这种霉菌毒素也可能是北非间质性肾病的病因。

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