Dietary fats altered nephrotoxicity profile of methylmercury in rats

Abstract

Weanling male Sprague-Dawley rats were administered semi-purified isocaloric diet containing soy oil (SO), seal oil (SE), docosahexaenoic acid (DHA), fish oil (FO) or lard (LA) for 28 days, and then gavaged with 0, 1 or 3 mg MeHg kg(-1) body weight per day and fed the same diet for 14 days. Serum and 24 h urine samples were collected on the day of necropsy, and analyzed for markers of kidney function and diseases. Kidney slices were analyzed for para-amino-hippurate (PAH) and tetraethylammonium (TEA) uptake, total mercury and MeHg content, and examined for pathological lesions. Total mercury and MeHg contents increased significantly and dose-dependently in all dietary groups. MeHg significantly increased relative kidney weight in all groups, serum creatinine in all except SO group, serum uric acid in the DHA and LA groups, serum Mg in all except the LA group, and urinary protein in the SO group. MeHg significantly decreased serum urea nitrogen in SE, FO and LA groups, urinary creatinine in the DHA group, PAH uptake in all except the SE group, and TEA uptake in all groups. MeHg caused nephrosis in all dietary groups. MeHg also significantly increased neutrophil counts in all except the SE group, decreased serum albumin and triglyceride in all except the DHA group, and increased serum total cholesterol in all groups, suggesting a nephrotic syndrome-like outcome. These results confirmed that kidney tubules are major targets of MeHg nephrotoxicity. Treatment with dietary fats did not prevent, but rather altered the profile of, nephrotoxicity of MeHg in rats.

Does Methylmercury-Induced Hypercholesterolemia Play a Causal Role in Its Neurotoxicity and Cardiovascular Disease?

“…Interestingly, concomitant treatment with DHA did not change MeHg-induced dyslipidemia. Although the beneficial nutrient of fish oil (DHA) was unable to abolish the deleterious (particularly, dyslipidemic) effects of MeHg, our data do not necessarily contradict the growing body of literature showing the beneficial effects of fish n-3 PUFA against MeHg toxicity (Jin et al, 2009;Kaur et al, 2008). Although the DHA dosage used in our protocol (8 mg/kg) has been shown to display beneficial (anti-inflammatory and renoprotective) effects in mouse models (Kielar et al, 2003) and is near to the recommended intake of DHA + EPA for adult humans (Kris-Etherton et al, 2002), the potential beneficial effects of a higher dose (or longer treatment period) of DHA on MeHg-induced hypercholesterolemia in our experimental model cannot be ruled out.…”

Experimental research Concomitant protective and therapeutic role of verapamil in chronic mercury induced nephrotoxicity in the adult rat: histological, morphometric and ultrastructural study

“…It is well known that mercury has a nephrotoxic effect [ 7 ] which can occur at low exposure levels [ 8 ]. This toxicity affects primarily the proximal convoluted tubules (PCT) [ 9 , 10 ].…”

Simultaneous Effects of Green Tea Extracts and Fish Oil on Mercury Accumulation and Antioxidant Defenses in Methylmercury-exposed Adult Mice

“…In contrast, n-3 polyunsaturated fatty acids (PUFA) contained in fish improve brain function (Guesnet et al, 2011;Mourek and Mourek, 2011) and reduce the risk of cardiovascular diseases (Cottin et al, 2011). Some reports indicate that dietary fat can influence oxidative DNA damage, nephrotoxicity, and steroidogenic enzyme activities after MeHg exposure (Grotto et al, 2011;Jin et al, 2008Jin et al, , 2009McVey et al, 2008). However, the human diet varies widely, and some reports have shown that foodstuffs other than seafood may also prevent MeHg toxicity and accumulation (Abdalla et al, 2010;Farina et al, 2005;Lee et al, 1999;Rowland et al, 1986;Sumathi et al, 2012).…”