Mantle Peter, Upadhyay Rohit, Herman Diana, Batuman Vecihi
Centre for Environmental Policy, Imperial College London, London SW7 2AY, UK.
Section of Nephrology and Hypertension, John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Int J Mol Sci. 2025 May 9;26(10):4553. doi: 10.3390/ijms26104553.
During the 70 years since the Balkan endemic nephropathy was recognised, failure to make a universal diagnostic cause continues for some critical researchers. Claims for cause by toxic molecules from microorganisms and/or plants are difficult to verify experimentally in retrospect, partly because no lifetime human experimentation is possible and partly since no experimental source is a convincing model. Apoptosis as a primary step in human nuclear decline has been a source of experiments for many years. Now, one has been used, which employs the detection of abnormal nuclear hydroxyls by using an Abcam histology protocol. Recent access to a few human tissues diagnosed for the Balkan nephropathy has enabled preliminary exploration to publish some positive human manifestations of apoptosis. Parallel use and positive findings have also now illustrated applications to experimental rats' kidneys after daily dietary exposure to ochratoxin A in lifetime experiments. Focus on renal cortical nephrons and their nuclei reveals a TUNEL-stained pattern with intensity linked to many months of the sub-clinical ochratoxin dietary exposure. The pattern survives long after exposure, but where experimental rats have internally developed cancer did not arise outside the kidney. Our experimental rat findings could not attribute the mechanism for the very different human urothelial tumours to traces of dietary ochratoxin A, but the present study encourages the exploration of more archived Balkan nephropathy renal cases to predict the focal urothelial origin of early tumours.
自巴尔干地方性肾病被发现的70年来，一些关键研究人员仍未能找到通用的诊断病因。微生物和/或植物产生的有毒分子导致该病的说法难以通过回顾性实验来验证，部分原因是不可能进行人体终身实验，部分原因是没有实验来源能成为令人信服的模型。细胞凋亡作为人类细胞核衰退的首要步骤，多年来一直是实验的来源。现在，有一种方法被采用，即使用艾博抗公司的组织学检测方案来检测异常的核羟基。最近获得了一些被诊断为巴尔干肾病的人体组织，这使得初步探索得以进行，并发表了一些关于细胞凋亡的人体阳性表现。同时使用该方法并得到的阳性结果也表明，在终身实验中，每天给实验大鼠喂食赭曲霉毒素A后，该方法可应用于大鼠肾脏。对肾皮质肾单位及其细胞核的研究发现，经TUNEL染色后的模式强度与亚临床赭曲霉毒素饮食暴露的时长相关。这种模式在暴露后很长时间内仍然存在，但在实验大鼠体内发生癌症的部位并未出现在肾脏之外。我们对实验大鼠的研究结果无法将人类截然不同的尿路上皮肿瘤的发病机制归因于饮食中痕量的赭曲霉毒素A，但本研究鼓励对更多存档的巴尔干肾病肾脏病例进行探索，以预测早期肿瘤的局灶性尿路上皮起源。
