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Fluoride-induced hepatotoxicity is prevented by L-Arginine supplementation via suppression of oxidative stress and stimulation of nitric oxide production in rats

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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, 100 and 200 mg kg−1, 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.

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Fig. 1
Fig. 2
Fig. 3
Fig. 4

taken from the liver of control rats treated with distilled water only and shows normal appearance of hepatic architecture, with no visible lesions. Plate B shows a section taken from the liver of rats exposed to sodium fluoride alone, with the major lesions comprising atrophy of the centrilobular hepatic cords and accompanying sinusoidal dilatation and enlarged central vein (encircled), giving a generalized “mosaic” pattern of the liver parenchyma. Plates C and D represent liver sections taken from rats treated with L-Arg at 100 and 200 mg kg−1, respectively, along with NaF exposure. These sections showed no visible lesions

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Acknowledgements

The authors wish to acknowledge the technical assistance provided by Mr. O. Agboola of the Department of Veterinary Physiology and Biochemistry, University of Ibadan.

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Authors and Affiliations

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

    Akinleye S. Akinrinde & Ademola A. Oyagbemi

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

    Monsuru Tijani

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

    Olusola A. Awodele

Authors
  1. Akinleye S. Akinrinde
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  2. Monsuru Tijani
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  3. Olusola A. Awodele
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  4. Ademola A. Oyagbemi
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Contributions

AAS and AAO contributed to the conceptualization and design of the study; AAS and MT did the analysis and interpretation of the data; AAS wrote the first draft of the manuscript; AAS and AAO did the critical revision of the manuscript. AAS, MT and OAA carried out the experimental assays.

Corresponding author

Correspondence to Akinleye S. Akinrinde.

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Conflict of interest

Akinleye Akinrinde, Monsuru Tijani, Olusola Awodele and Ademola Oyagbemi declare that they have no conflict of interest.

Ethical approval

The study was conducted following guidelines approved by the Animal Care and Use Research Ethics Committee (ACUREC) of the University of Ibadan (Approval number: UI-ACUREC/19/124). The conduct of the experiments, humane animal handling and welfare was guided by protocols contained in the publication of the National Institute of Health, “Guide for the Care and Use of Laboratory Animals.

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Akinrinde, A.S., Tijani, M., Awodele, O.A. et al. Fluoride-induced hepatotoxicity is prevented by L-Arginine supplementation via suppression of oxidative stress and stimulation of nitric oxide production in rats. Toxicol. Environ. Health Sci. 13, 57–64 (2021). https://doi.org/10.1007/s13530-020-00070-6

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