Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract Tumours

Abstract

This review addresses the unresolved aetiology of several nephropathies and associated upper tract tumours diagnosed all over the world, but especially in the Balkan regions. Studies conducted over the last 35 years point to mycotoxins, mainly ochratoxin A (OTA) as the main culprit. Recent theories however have implicated aristolochic acids (AA). The aim of this review is to put forward arguments in favour of the mycotoxin theory and to show the incoherence of the AA theory. It discusses the differences between the epidemiology of Balkan endemic nephropathy (BEN) and aristolochic acid nephropathy (AAN); OTA and AA carcinogenicity; clinical and pathological effects induced by OTA and AA; sources of OTA contamination (food, air, drinking water); OTA-and AA-DNA adduct formation; the role of genetic polymorphisms ; and the risk for young children.

Limitations and plausibility of the Pliocene lignite hypothesis in explaining the etiology of Balkan endemic nephropathy

“…Other environmental agents are more plausible Other environmental agents may be more plausible as etiological factors than exposure to Pliocene lignites, i.e., exposure to ochratoxin A, a fungal mycotoxin, 15,40,50,51 and aristolochic acid from Aristolochia clematitis seeds, 11 for which there has been much renewed interest. 44,[52][53][54] However, ochratoxin A contamination has been found in both endemic and nonendemic regions, 22,55,56 nonaffected households, 57 and in Romania, no ochratoxin A or its degradation products were detected in the urine of BEN patients, 58 raising doubts about its role in the etiology of the disease.…”

Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

“…OTA possesses a chlorophenolic group, and chlorophenols are well known to undergo oxidative dechlorination reactions to afford quinone/ hydroquinone redox couples (15,16). The hydroquinone metabolite (OTHQ, Figure 1) of OTA has been detected in the urine (17) and kidneys (18) of rats, and in human blood and urine samples (19). Oxidation of OTHQ generates the quinone electrophile OTQ that reacts with DNA to generate covalent DNA adducts, as evidenced using 32 P-postlabeling (20).…”

Mycotoxicoses in children

“…So far, no ochratoxicosis has been reported in children. Some researchers believe that OTA is involved in the development of Balkan endemic nephropathy (BEN) and otherwise rare urothelial tumours, whose incidence is high in the endemic regions of the Balkans (68,69). In several studies performed in the endemic regions of Bulgaria and Croatia the level of OTA or the frequency of OTA-positive food and human blood samples were higher than in control regions (for a more comprehensive review see 70).…”