Fluoride-induced hepatotoxicity is prevented by L-Arginine supplementation via suppression of oxidative stress and stimu

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ORIGINAL ARTICLE

Fluoride‑induced hepatotoxicity is prevented by L‑Arginine supplementation via suppression of oxidative stress and stimulation of nitric oxide production in rats Akinleye S. Akinrinde1 · Monsuru Tijani2 · Olusola A. Awodele3 · Ademola A. Oyagbemi1 Accepted: 2 September 2020 © Korean Society of Environmental Risk Assessment and Health Science 2020

Abstract Objective  Concerns over fluoride toxicity have increased in recent times due to high exposures from various anthropogenic sources such as industrial sites, fluoride-containing pesticides, drugs, dental products, refridgerants and fire extinguishers. There is, therefore, continued search for agents that could ameliorate the toxicity of this chemical in various body organs. In this study, we sought to investigate the protective effects of L-Arginine (L-Arg), a nitric oxide donor, on liver toxicity induced by sodium fluoride (NaF) in rats. Methods  Rats received NaF (300 mg L ­ −1) in drinking water alone or in co-treatment with L-Arg at two different doses, −1 100 and 200 mg kg , by oral gavage, for 7 days. Markers of hepatotoxicity, oxidative stress and antioxidant status were thereafter assessed. Results  NaF caused marked increase in serum transaminases: alanine aminotransferase, Aspartate aminotransferase and Alkaline phosphatase, along with atrophy of the centri-lobular hepatic cords and dilatation of the sinusoids. Moreover, NaF stimulated increases in hepatic contents of hydrogen peroxide ­(H2O2), nitric oxide (NO), protein carbonyls, malondialdehyde and advanced oxidation protein products. NaF also inhibited the activities of antioxidant enzymes, Glutathione peroxidase and Superoxide dismutase. However, L-Arg supplementation caused significant alleviation of NaF hepatotoxicity by reducing lipid and protein oxidation indices, stimulation of antioxidant systems along with increased production of NO. Conclusions  L-Arg showed promise as a potential protective agent against NaF-induced hepatotoxicity via restoration of oxidant-antioxidant balance. Further studies are required to understand the involvement of NO signaling in the protective effects of L-Arg against fluoride toxicity. Keywords  Fluoride · Arginine · Nitric oxide · Liver damage · Oxidative stress

Introduction Fluoride is a widespread environmental contaminant which is naturally released via leaching from rocks and soils into groundwater, thereby contaminating drinking water, with * Akinleye S. Akinrinde [email protected] 1



Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria

2



Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria

3

Department of Veterinary Laboratory Technology, Federal College of Animal Health and Production Technology, Moor Plantation, Ibadan, Nigeria



potential human and animal exposures [1]. In addition, fluoride ions are components of some dental health products, insecticides, drugs, as well as vapors from industriall