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Effects of N-Acetyl Cysteine on Genes Expression of c-myc, and Ask-1, Histopathological, Oxidative Stress, Inflammation, and Apoptosis in the Liver of Male Rats Exposed to Cadmium

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Abstract

This study aimed to consider the oxidative damage induced by cadmium (Cd) and apoptosis and the role of N-acetylcysteine (NAC) in preserving hepatic cells against Cd toxicity. Male rats were randomly divided into seven groups including 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). Hepatic cells apoptosis was measured using TUNEL assay method. Levels of malondialdehyde (MDA), TNF-α, IL-10, and total antioxidant capacity (TAC) were measured by specific kits. Expression of c-myc and Ask-1 genes was considered using RT-PCR. NAC treatments significantly improved TAC and IL-10, but decreased MDA and TNF-α values in rats that were exposed to a single and continuous dose of Cd (p < 0.05). Exposure to a single and continuous dose of Cd caused a significant increase in c-myc expression by 3.76-fold (p < 0.001) and 8.17-fold (p < 0.0001), respectively. Single and continuous dose treatment of Cd led to a significant increase in Ask1 expression by 4.38-fold (p < 0.001) and 13.52-fold (p < 0.001), respectively. NAC treatments significantly decreased the expression of c-myc, and Ask-1 in rats exposed to single or continuous Cd. Cd exposure is strongly associated with oxidative stress, inflammation, antioxidant depletion, and liver cells apoptosis. NAC can protect liver tissue against Cd by elevating antioxidants capacity, mitigating oxidative stress and inflammation, as well as down-regulating of apoptotic genes.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thanks Dr. Mohammad Mahdi Jafarzadeh and Nima Rahmani Talatapeh from Islamic Azad University (Rasht Branch) and Asgar Beigi from Shahid Beheshti University of Medical Sciences for their cooperation in this research.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Conceptualization: BA and AS; Methodology: AS; Formal analysis and investigation: BA, AS, NR and AA; Writing - Original Draft Preparation: BA, AS; Editing: AS, NR and AA; Resources: BA; Supervision: AS, NR and AA.

Corresponding author

Correspondence to Ali Salehzadeh.

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This experimental study was approved by the animal care and use committee at the Islamic Azad University, Rasht branch (Approval ID: IR.IAU.RASHT.REC.1399.011).

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The authors declare no competing interests.

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Alizadeh, B., Salehzadeh, A., Ranji, N. et al. Effects of N-Acetyl Cysteine on Genes Expression of c-myc, and Ask-1, Histopathological, Oxidative Stress, Inflammation, and Apoptosis in the Liver of Male Rats Exposed to Cadmium. Biol Trace Elem Res 200, 661–668 (2022). https://doi.org/10.1007/s12011-021-02670-w

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