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The effect of N-Acetyl cysteine on the expression of Fxr (Nr1h4), LXRα (Nr1h3) and Sirt1 genes, oxidative stress, and apoptosis in the liver of rats exposed to different doses of cadmium

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Abstract

The aim of this study was to consider the expression of farnesoid X receptor (Fxr), liver X receptor (LXRα) and sirtuin 1 (Sirt1), oxidative stress, inflammation, apoptosis, and the protective role of N-acetylcysteine (NAC) in the liver of rats treated with cadmium (Cd). 30 Wistar rats were divided into 5 groups: G1 (control), G2 (single dose of Cd), G3 (continuous dose of Cd), G4 (single dose of Cd + continuous dose of NAC), and G5 (continuous dose of Cd + continuous dose of NAC). The apoptosis of hepatic cells was measured using the TUNEL assay. Levels of malondialdehyde (MDA), IL-10, TNF-α, and total antioxidant capacity (TAC) were measured by specific kits. The expression of Fxr, LXRα, and Sirt1 genes and ratio of Bax/Bcl2 was considered using RT-PCR. While NAC treatment improved TAC and IL-10 values, it decreased MDA and TNF-α levels in the liver of rats exposed to Cd (P < 0.001). NAC decreased Bax/Bcl2 in the liver of G4 and G5 groups (P < 0.001). Exposure to a continuous dose of Cd decreased Fxr, LXRα, and Sirt1 expression by 36.65- (P < 0.001), 12.52- (P < 0.001) and 11.34-fold (P < 0.001) compared to control, respectively. NAC increased Fxr, LXRα, and Sirt1 expression (P < 0.01) and decreased Cd concentrations in both serum and tissue samples in G4 and G5 groups. Our results suggested that NAC protects liver tissue against Cd toxicity by elevating antioxidant capacity, mitigating oxidative stress, inflammation, apoptosis and up-regulation of FXR, LXR, and SIRT1 genes.

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Acknowledgement

The authors are thankful to Dr. Sogol Meknatkhah (Institute of Biochemistry and Biophysics (IBB), University of Tehran), Dr. Ali Rahbari (Pathologist, Jam Hospital) and Dr. Armaghan Shirinsokhan (Rasht Branch, Islamic Azad University) for all of their helps and supports.

Funding

Hereby, we thank Islamic Azad University (Rasht Branch) (Grant No. 17/16/4/16035) for providing the project costs.

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, P.O. Box, 3516-41335, Rasht, Iran

    Zahra Azarmehr, Najmeh Ranji & Hadi Habibollahi

  2. Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran

    Zeinab Khazaei Koohpar

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  1. Zahra Azarmehr
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Contributions

ZA, NR and HH contributed to the conception and design of this article. ZA and NR contributed to analysis and interpretation. ZA, NR and ZKK were involved in statistical analysis. ZA, NR and HH contributed in writing and provided critical revision for this article. NR gave final approval for this article. All authors agree to be accountable for all aspects of the work.

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Correspondence to Najmeh Ranji.

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This experimental study was approved by the animal care and use committee at Islamic Azad University, Rasht branch, Iran (Approval ID: IR. IAU. RASHT. REC. 1399.008).

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Azarmehr, Z., Ranji, N., Khazaei Koohpar, Z. et al. The effect of N-Acetyl cysteine on the expression of Fxr (Nr1h4), LXRα (Nr1h3) and Sirt1 genes, oxidative stress, and apoptosis in the liver of rats exposed to different doses of cadmium. Mol Biol Rep 48, 2533–2542 (2021). https://doi.org/10.1007/s11033-021-06300-5

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