Kumar Manoj, Dwivedi Prabhaker, Sharma Anil Kumar, Sankar Muthu, Patil Rajendra Damu, Singh Nittin Dev
1Division of Pathology, Indian Veterinary Research Institute, Izatnagar, India.
Toxicol Ind Health. 2014 Feb;30(1):90-8. doi: 10.1177/0748233712452598. Epub 2012 Jul 6.
Ochratoxin A (OTA) and citrinin (CIT) are nephrotoxic mycotoxins produced mainly by fungal species Aspergillus ochraceus and Penicillium citrinum, respectively, which have been found to occur together in various food and feed commodities. In the present study, both OTA and CIT were evaluated for their potential to induce oxidative damage by determining lipid peroxidation (LPO) through malondialdehyde (MDA) assay and apoptosis by flow cytometry, gel electrophoresis and renal ultrastructural morphology in rabbits fed with diets containing OTA (0.75 mg/kg feed), CIT (15 mg/kg feed) and OTA + CIT (0.75 and 15 mg/kg feed, respectively) up to 60 days. The concentration of MDA was found significantly higher in OTA and combination-treated groups. OTA and combination-treated groups revealed more apoptotic cells in flow cytometry when compared with the CIT-treated group. Characteristic DNA fragmentation, as evidenced by ladder pattern in electrophoresis appeared in the toxin-treated groups. Ultrastructurally, interstitial cells showed nuclear fragmentation and cytoplasmic blebbing in OTA- and CIT-treated groups; whereas, proximal convoluted tubular epithelial cells, besides interstitial cells, showed nuclear fragmentation in the combined treatment group. The results suggested that low concentrations of OTA and CIT either alone or in combination induced apoptosis in a time-dependent manner and LPO in the rabbit kidney, which appeared to play a major role in the pathogenesis of nephrotoxicity. Furthermore, the interaction of these two nephrotoxic mycotoxins was found to be additive.
赭曲霉毒素A（OTA）和桔霉素（CIT）是具有肾毒性的霉菌毒素，分别主要由曲霉属真菌和桔青霉产生，已发现它们共同存在于各种食品和饲料中。在本研究中，通过丙二醛（MDA）测定法测定脂质过氧化（LPO）以及采用流式细胞术、凝胶电泳和肾脏超微结构形态学方法，对喂食含OTA（0.75毫克/千克饲料）、CIT（15毫克/千克饲料）和OTA + CIT（分别为0.75和15毫克/千克饲料）的日粮长达60天的兔子，评估了OTA和CIT诱导氧化损伤的潜力。发现OTA组和联合处理组的MDA浓度显著更高。与CIT处理组相比，OTA组和联合处理组在流式细胞术中显示出更多的凋亡细胞。电泳中呈现的梯状条带证明，毒素处理组出现了特征性的DNA片段化。超微结构上，OTA和CIT处理组的间质细胞出现核碎片化和细胞质起泡；而在联合处理组中，除间质细胞外，近端曲管上皮细胞也出现核碎片化。结果表明，低浓度的OTA和CIT单独或联合使用均以时间依赖性方式诱导兔肾细胞凋亡和脂质过氧化，这似乎在肾毒性发病机制中起主要作用。此外，发现这两种肾毒性霉菌毒素的相互作用具有相加性。
