Possible health impacts of naturally occurring uptake of aristolochic acids by maize and cucumber roots: links to the etiology of endemic (Balkan) nephropathy

Abstract

Aristolochic acids (AAs) are nephrotoxic and carcinogenic derivatives found in several Aristolochia species. To date, the toxicity of AAs has been inferred only from the effects observed in patients suffering from a kidney disease called "aristolochic acid nephropathy" (AAN, formerly known as "Chinese herbs nephropathy"). More recently, the chronic poisoning with Aristolochia seeds has been considered to be the main cause of Balkan endemic nephropathy, another form of chronic renal failure resembling AAN. So far, it was assumed that AAs can enter the human food chain only through ethnobotanical use (intentional or accidental) of herbs containing self-produced AAs. We hypothesized that the roots of some crops growing in fields where Aristolochia species grew over several seasons may take up certain amounts of AAs from the soil, and thus become a secondary source of food poisoning. To verify this possibility, maize plant (Zea mays) and cucumber (Cucumis sativus) were used as a model to substantiate the possible significance of naturally occurring AAs' root uptake in food chain contamination. This study showed that the roots of maize plant and cucumber are capable of absorbing AAs from nutrient solution, consequently producing strong peaks on ultraviolet HPLC chromatograms of plant extracts. This uptake resulted in even higher concentrations of AAs in the roots compared to the nutrient solutions. To further validate the measurement of AA content in the root material, we also measured their concentrations in nutrient solutions before and after the plant treatment. Decreased concentrations of both AAI and AAII were found in nutrient solutions after plant growth. During this short-term experiment, there were much lower concentrations of AAs in the leaves than in the roots. The question is whether these plants are capable of transferring significant amounts of AAs from the roots into edible parts of the plant during prolonged experiments.

An Integrated View of Aristolochic Acid Nephropathy: Update of the Literature

“…BEN is described as a familial clustering and slowly progressive kidney disease. The clinical signs and symptoms of BEN are non-specific and often remain latent for years even decades until a significant decline in function occurs [47,49,50]. After an initial asymptomatic stage, patients suffer from weakness and lassitude, mild lumbar pain and pallor of the skin [45,50].…”

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

“…45 For example, the plants are widespread in many regions of Romania, including those with similar rural populations and ethnic groups as BEN endemic areas, yet the regions have no identified cases of nephropathy. 59 Moreover, human exposure to A.…”

“…25,51 For instance, A. clematitis seed bulbs would have been separated from wheat grain by the modern mechanized mills in use for many years in the endemic regions of Croatia and Bulgaria, 60 and in use for decades in the endemic regions of Romania. 59 In addition, in Romania, wheat has only been grown sporadically, 59 maize is the dominant cereal, and it cannot be contaminated by aristolochic acid 51 in the same way as wheat. Also, although uptake of an aristolochic acid solution by maize roots has recently been demonstrated, 59 differential uptakes by crop plants between endemic and nonendemic regions, for example, appears unlikely.…”

“…59 In addition, in Romania, wheat has only been grown sporadically, 59 maize is the dominant cereal, and it cannot be contaminated by aristolochic acid 51 in the same way as wheat. Also, although uptake of an aristolochic acid solution by maize roots has recently been demonstrated, 59 differential uptakes by crop plants between endemic and nonendemic regions, for example, appears unlikely. Furthermore, though an epidemiological study showed that exposure to A. clematitis has occurred in endemic areas via other routes, i.e., from teas and baths prepared for therapeutic purposes, the majority of BEN patients had not used such remedies.…”

“…64 For example, a stable incidence 65 and prevalence of BEN over a period of decades has been reported for the Kolubara region (the most affected) in Serbia, 66 and for Romania, where modern harvesting and herbicide application methods have been extensively employed for decades. 59 Moreover, the disease may be increasing, for instance: tumors of the renal pelvis and ureter have been increasing in endemic regions; 20 there has been a gradual involvement of more villages and households affected by BEN and urinary tract tumors in the Vratza District, Bulgaria, 67 and; in the recent (y1995-2009) years in Serbia incidence of BEN has also been reported as increased. 64 However, there have also been reports of decreasing incidence 68 and prevalence 69 in the Vratza region (and decreasing incidence in Serbia), 70 but these may be due to flaws in the surveillance system, and/or prophylactic measures, e.g., population redistribution.…”