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Hepatoprotective Effect of Nicotinamide Versus Lead-Motivated Hepatotoxicity in Rats via Correcting Effect on Nuclear Factor-kβ Pathway and Glutathione Metabolism

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Abstract

Lead (Pb) poisoning is one of the pivotal environmental issues and prompts liver dysfunction by elevating oxidative stress and inflammation. Nicotinamide (NA) deficiency enhances sensitivity to Pb toxicity. So, we investigated the effect of nicotinamide (NA) on the rat’s liver histopathological and biochemical profiles in a rat model of Pb toxicity. Thirty-six rats were divided into four groups (nine rats at each): normal (N), lead toxicity (Pbt), and NA-treated N and Pbt groups. Treated groups took NA (180 mg/L in drinking water for one month). Pb intoxication was motivated in rats by acquiring 50 mg/L lead acetate in drinking water. Oxidative stress markers (advanced oxidation protein products and malondialdehyde), antioxidant markers (total glutathione, reduced glutathione to oxidized glutathione ratio, ferric ion reducing power, catalase, and paraoxonase-1), and inflammatory markers (hepatic nuclear factor-kβ expression, interleukin 1β level, and myeloperoxidase activity) in sera and liver homogenates were determined. In addition, the biochemical parameters of the liver function were measured. Finally, the liver of rats was evaluated by histopathological observation. NA corrected lead-persuaded biochemical and histopathological changes in the rat’s liver. In addition, treatment decreased Pb, oxidative stress, and inflammatory markers in the sera and liver homogenates of N and Pbt groups. In addition, it elevated antioxidant markers (p < 0.001). NA prevented Pb-induced liver histopathological alternations and reduced liver dysfunction by reducing Pb, oxidative stress, and inflammation. Moreover, raising GSH/GSSG and diminishing the hepatic NF-kβ pathway are cardinal mechanisms of the treatment against Pb-motivated hepatotoxicity in rats.

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Acknowledgements

The results explained in this paper were part of the student thesis.

Funding

The authors are thankful to Ardabil University of medical sciences for financial support.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Ardabil University of Medical Sciences, Ardabil, Iran

    Sina Mahdavifard

  2. Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

    Zahra Shahi

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  1. Sina Mahdavifard
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  2. Zahra Shahi
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Contributions

1) Study plan, evaluation and exegesis of data: Mahdavifard & Shahi

2) Manuscript writing and revising: Mahdavifard

3) Ultimate sanction of the version to be submitted and any revised version: Mahdavifard & Shahi

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Correspondence to Sina Mahdavifard.

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Mahdavifard, S., Shahi, Z. Hepatoprotective Effect of Nicotinamide Versus Lead-Motivated Hepatotoxicity in Rats via Correcting Effect on Nuclear Factor-kβ Pathway and Glutathione Metabolism. Biol Trace Elem Res (2023). https://doi.org/10.1007/s12011-023-03980-x

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