title: Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation.
abstract: The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.
authors: Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, 62514 Beni-Suef, Egypt.
authors: Ayman M
authors: AM
authors: Mahmoud
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D003520:Cyclophosphamide / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism*; D017208:Rats, Wistar; D000637:Transaminases / Q000097:blood; D015854:Up-Regulation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D016207:Cytokines; D047495:PPAR gamma; D009569:Nitric Oxide; D003520:Cyclophosphamide; D006569:Hesperidin; D000637:Transaminases; D005978:Glutathione
keywords: NF-κB; PPAR; PPARs; chemotherapy; chimiothérapie; cytokines; flavonoids; flavonoïdes