Single and combined effect of fluoride and hardness of drinking water on nephrotoxicity: <em>in-vivo</em> study using Wistar rats as an animal model

Abstract

Drinking water in areas with a high prevalence of chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka is known to have high concentrations of fluoride and hardness. The present study evaluated the individual and combined effects of water hardness and fluoride on potential nephrotoxicity, using Wistar rats as an animal model. Thirty-five Wistar rats were randomly assigned into five groups (n=7). Test groups F, H, RL, and RH were given de-ionized water containing 1.5 mg/L fluoride, 200 mg/L hardness, 1.5:200 mg/L fluoride: hardness, and 5:800 mg/L fluoride: hardness respectively, while control group C was given de-ionized water. Body weight and daily water consumption were measured. Serum creatinine, urine creatinine, and urinary biomarker KIM-1 were analyzed. Histopathological changes in the kidneys were observed. There were no significant differences in body weights (p>0.05) while daily water consumption was reduced significantly in the test groups RL and RH (p<0.05). A significant increment in serum creatinine in the RL and RH groups (p<0.05), and a significant reduction in urine creatinine in the F, H, RL and RH groups (p<0.05), were recorded compared to the control. However, the highest magnitude of the effect on serum creatinine and urine creatinine was recorded in the RL group. Significant increment in KIM-1 levels were recorded in the RH group (p<0.05) while the RH group indicated a more rapid increment from the 28th day. When considering histopathology, renal tubular changes were observed in the test groups. The individual and combined effects of water hardness and fluoride may contribute to the aetiology of CKDu in Sri Lanka.