Antioxidants inhibition of high plasma androgenic markers in the pathogenesis of ethylene glycol (EG)-induced nephrolithiasis in Wistar rats

Abstract

The association between serum gonadal steroids and urolithiasis in males received only limited attention. Calcium oxalate urolithiasis is induced by administration of ethylene glycol in drinking water. It appears that the administration of natural antioxidants has been used to protect against nephrolithiasis in human and experimental animals. The purpose is to study the potential role of antioxidants as inhibitors of high plasma androgenic markers or hyperandrogenicity in the pathogenesis of ethylene glycol-induced nephrolithiasis in Wistar rats. Male Wistar rats were studied in 4-week period. Group 1 (control) was fed a standard commercial diet. Group 2 received the same diet with 0.5 % of ethylene glycol. Group 3 received EG plus the diet and water added with antioxidant nutrients and lime juice as the dietary source of citrate. Group 4 and Group 5 were treated similar to Group 2 and Group 3 with 0.75 % of ethylene glycol. For antioxidant supplementation, the standard diet enriched with 4,000.0 μg vitamin E and 1,500.0 IU vitamin A for each rat per day added to the diet once a week, and provided daily with 5.0 mg vitamin C, 400.0 μg vitamin B6, 20.0 μg selenium, 12.0 mg zinc, and 2.0 mg boron for each rat per day in their drinking water. After treatment period, collection of blood was performed and kidneys were removed and used for histopathological examination. The results based on various assays, measuring size of crystal deposition, and histological examinations showed that high concentration of androgens acts as promoter for the formation of renal calculi due to ethylene glycol consumption and the inhibitory role of antioxidant complex in the formation of renal calculi disease. Data revealed that the size and the mean number of crystal deposits determined in EG 0.75 % treated groups (G4) were significantly higher than the EG-treated groups, added with antioxidant nutrients and lime juice (G5). The mean concentration of androgens in Group 4 increased after EG 0.75 % administration, and decreased after antioxidants supplementation in Group 5. Elevated concentration of androgens (as promoters of the formation of renal calculi) as a result of EG consumption and their decreasing following antioxidant supplementations along with the slight decrease in malondialdehyde level provides a scientific rational for preventive and treatment roles of antioxidant nutrient complex in kidney stone disease.

In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of LPR on urinary risk factors for kidney stone formation in healthy volunteers

“…Antioxidant intervention has been proved to inhibit the development of kidney stone at least in the animal model [39]. In this study, we provided an evidence of antioxidant property of LPR for inhibiting ROS generation in HK-2 cells challenged with lithogenic COM crystals.…”

Possible role of elevated serum testosterone in pathogenesis of renal stone formation

“…[7] and Watson et al . [10] that serum total testosterone levels tend to be in higher range in urolithiatic patients than controls.…”

“…[5] The upregulation of androgen receptors in patients with urolithiasis,[6] higher androgen levels in renal stone patients and low urinary oxalate excretion in castrated males further augment the possible role of male sex hormones in the pathogenesis of urolithiasis. [7]…”

Genetic Variations rs859, rs4646, and rs372883 in the 3′-Untranslated Regions of Genes Are Associated with a Risk of IgA Nephropathy

“…CYP19A1 is part of a cluster of cytochrome P450 genes on chromosome 15q21.1, which is responsible for the biosynthesis of androgens and estrogen [20]. Some animal experiments and clinical observations have demonstrated that the occurrence of kidney disease is related to the levels of sex hormones throughout the body [21, 22]. Therefore, it is not surprising that CYP19A1 is associated with IgAN.…”