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Protective effect of arbutin against cyclophosphamide-induced oxidative stress, inflammation, and hepatotoxicity via Nrf2/HO-1 pathway in rats

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Abstract

Cyclophosphamide (CP) is a potent anticancer drug widely employed in chemotherapy against various types of cancer. However, CP leads to toxicity to non-targeted organs, including the liver and this limits its clinical use. This study explored the role of arbutin (ARB) against CP-mediated oxidative and inflammatory reactions and hepatotoxicity. Rats were administered ARB (25 and 50 mg/kg) for 14 days and CP (150 mg/kg). CP triggered liver tissue injury with marked increase in serum AST, ALT, ALP, and bilirubin, and hepatic malondialdehyde (MDA) and nitric oxide (NO) coupled with diminution of GSH, SOD, catalase, and GPx. Liver NF-kB p65, NOS, IL-6, TNF-α, Bax and caspase-3 were upregulated by CP injection and IL-10 and Bcl-2 were decreased. ARB prevented liver injury, suppressed MDA, NO, NF-kB p65, inflammatory markers, Bax and caspase-3 in CP-treated rats. ARB restored antioxidants, IL-10 and Bcl-2, and enhanced Nrf2 and hemeoxygenase-1 (HO) both gene and protein in the liver of rats. In conclusion, these results pinpointed the protective role of ARB on oxidative and inflammatory reactions, apoptosis, and hepatotoxicity in rats. This hepatoprotective activity was linked to the ability of ARB to modulate Nrf2/HO-1 pathway.

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Acknowledgements

Princess Nourah bint Abdulrahman University Researchers Supporting Project Number (PNURSP2023R381), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

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Princess Nourah bint Abdulrahman University Researchers Supporting Project Number (PNURSP2023R381), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, 11671, Saudi Arabia

    Reem S. Alruhaimi

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  1. Reem S. Alruhaimi
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Correspondence to Reem S. Alruhaimi.

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The experiment was conducted according to the guidelines of the National Institutes of Health (NIH publication No. 85–23, revised 2011) and was approved by the research ethics Committee at Princess Nourah bint Abdulrahman University (IRB Approval number: 23-0030).

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Alruhaimi, R.S. Protective effect of arbutin against cyclophosphamide-induced oxidative stress, inflammation, and hepatotoxicity via Nrf2/HO-1 pathway in rats. Environ Sci Pollut Res 30, 68101–68110 (2023). https://doi.org/10.1007/s11356-023-27354-x

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