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

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 MT...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 2020-08, Vol.393 (8), p.1405-1417
Main Authors: Abdelaziz, Ramadan M., Abdelazem, Ahmed Z., Hashem, Khalid S., Attia, Yasser A.
Format: Article
Language:English
Subjects:
Antioxidants
Apoptosis
Biomedical and Life Sciences
Biomedicine
Caspase-9
Catalase
Gene expression
Glutathione
Hepatotoxicity
Hesperidin
Inflammation
Malondialdehyde
Methotrexate
Neurosciences
NF-κB protein
Original Article
Oxidative stress
p53 Protein
Pharmacology/Toxicology
Rodents
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary: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.
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-020-01843-z