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Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats

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Abstract

Hesperidin (HD), a bioflavonoid, has been shown to exert hepatoprotective effects. Our aim is to investigate the possible protective effects of HD against methotrexate (MTX) hepatotoxicity in adult male Sprague-Dawley (SD) rats that were divided into four groups (10 rats/each) and were exposed to MTX with or without HD co-administration for consecutive 28 days. The results showed that HD significantly ameliorated MTX-induced increase in liver enzymes and histopathological changes. Hepatic oxidative stress was suppressed by HD, as evidenced by the decrease in malondialdehyde (MDA), with a concomitant increase in total antioxidant activity (TAC), catalase (CAT), and glutathione (GSH) levels. Moreover, co-administration of HD with MTX remarkably upregulated the expression of Nrf2 and HO-1 compared with the MTX group. By the decrease in nuclear factor-kB (NF-κB) pathway and tumor necrosis factor α (TNF-α), HD obviously attenuated inflammatory response in MTX-lesioned livers. Likewise, the downregulation of P53 by HD could explain its antiapoptotic effects as indicated by increase BCl2 and the significant decrease of caspase-9 mRNA expression as compared with the MTX group. Thus, these findings revealed the hepatoprotective nature of HD against MTX hepatotoxicity by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant aptitude.

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Acknowledgments

We would like to express special words of thanks with deepest appreciation to the team of this study. We would like to acknowledge Dr. Sherein Abdelgayed assistant professor of pathology at Faculty of Veterinary Medicine, Cairo University for useful participation in experimental research.

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Authors and Affiliations

  1. Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt

    Ramadan M. Abdelaziz & Ahmed Z. Abdelazem

  2. Biochemistry Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt

    Khalid S. Hashem

  3. National Institute of Laser Enhanced Sciences, Cairo University, Giza, 12613, Egypt

    Yasser A. Attia

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  1. Ramadan M. Abdelaziz
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  2. Ahmed Z. Abdelazem
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  3. Khalid S. Hashem
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  4. Yasser A. Attia
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Contributions

RA, YA, and KH conceived and designed research. RA and AA conducted experiments. KH contributed new reagents or analytical tools. RA and YA analyzed data and wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Ramadan M. Abdelaziz or Yasser A. Attia.

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This study protocol was approved by the Review Committee for Postgraduate Studies at Beni-Suef University, Egypt, and guidelines for the human care of the animals have been applied.

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The authors declare that they have no conflict of interest.

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Abdelaziz, R.M., Abdelazem, A.Z., Hashem, K.S. et al. Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1405–1417 (2020). https://doi.org/10.1007/s00210-020-01843-z

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