Experimental rat model for acute tubular injury induced by high water hardness and high water fluoride: efficacy of primary preventive intervention by distilled water administration

Abstract

Background: High water hardness associated with high water fluoride and the geographical distribution of Chronic Kidney Disease of unknown etiology (CKDu) in Sri Lanka are well correlated. We undertook this study to observe the effects of high water hardness with high fluoride on kidney and liver in rats and efficacy of distilled water in reducing the effects. Methods: Test water sample with high water hardness and high fluoride was collected from Mihinthale region and normal water samples were collected from Kandy region. Twenty-four rats were randomly divided into 8 groups and water samples were introduced as follows as daily water supply. Four groups received normal water for 60 (N1) and 90 (N2) days and test water for 60 (T1) and 90 (T2) days. Other four groups received normal (N3) and test (T3) water for 60 days and followed by distilled water for additional 60 days and normal (N4) and test (T4) water for 90 days followed by distilled water for another 90 days. The rats were sacrificed following treatment. Serum samples were subjected to biochemical tests; serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and elemental analysis. Histopathological examinations were carried out using kidney and liver samples. Results: Test water treated groups were associated with acute tubular injury with loss of brush border and test water followed with distilled water treated groups maintained a better morphology with minimal loss of brush border. Serum creatinine levels in T1 and T2 groups and urea level in T2 group were significantly (p < 0.05) increased compared to control groups. After administration of distilled water, both parameters were significantly reduced in T4 group (p < 0.05) compared to T2. Serum AST activity was increased in T4 group (p < 0.05) compared to control group with no histopathological changes in liver tissues. The serum sodium levels were found to be much higher compared to the other electrolytes in test groups.

Calcium ion adsorption of <em>Leucaena leucocephala</em> wood biochar activated with coconut vinegar

“…Higher fluoride levels common to all studied areas has been also observed, suggesting that high Ca 2+ activity aggravates the damage caused by fluoride, resulting in possible lesions on tubular cells of the kidney tissues. A recent study done by using rats, also supports this idea (Perera et. al.…”

<p>Purposeful Review to Identify Risk Factors, Epidemiology, Clinical Features, Treatment and Prevention of Chronic Kidney Disease of Unknown Etiology</p>

“…72 An experimental study revealed hard water with high fluoride content resulted in acute tubular injury and it can be minimized by administering distilled water. 73 In addition, high silica levels in drinking water from pesticides containing silica or as a result of leaching from bed rocks and the combination of silica, strontium and NSAIDs have been proposed to cause CKDu. 74…”

The Utility of Novel Renal Biomarkers in Assessment of Chronic Kidney Disease of Unknown Etiology (CKDu): A Review

“…Although the exact etiology is yet to be determined, several environmental, socio-economic, and occupational factors are strongly associated with CKDu. Studies have suggested a role for a multitude of contributing factors such as chronic low dose exposure to multiple heavy metals and agrochemicals [ 28 , 29 ], heat stress and recurrent dehydration [ 30 , 31 ], nephrotoxic pharmaceuticals [ 32 ], high fluoride levels and water hardness [ 33 ], hyperuricemia and hyperuricosuria [ 34 ], leptospirosis [ 35 ], and genetic predisposition [ 36 ]. Heat stress, coupled with dehydration, are considered key driving factors in Mesoamerican CKDu patients [ 12 , 37 ].…”

“…Additionally, the same substances have been found in urine, blood, hair, and nail samples collected from affected populations [ 14 , 47 , 48 ], providing strong evidence for an association with environmental toxins with renal diseases, including CKDu. Further, studies from multiple geographic regions suggest clear associations of groundwater fluoride and water hardness with the onset of renal diseases, including interstitial tubule damage [ 49 ] coupled with experimental validation through animal studies [ 33 ]. Certain nephrotoxic mycotoxins (e.g., aflatoxins, ochratoxins, fumonisins) and phytotoxins such as aristolochic acid, are other environmental factors known to cause chronic tubule-interstitial disease.…”