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: Ayman M Mahmoud
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 92 Issue 9 Pg. 717-24 (Sep 2014) ISSN: 1205-7541 [Electronic] Canada
• PMID: 25079140 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Alkylating
• Antioxidants
• Cytokines
• PPAR gamma
• Nitric Oxide
• Cyclophosphamide
• Hesperidin
• Transaminases
• Glutathione

Topics

• Animals
• Antineoplastic Agents, Alkylating (adverse effects)
• Antioxidants (pharmacology, therapeutic use)
• Chemical and Drug Induced Liver Injury (metabolism, prevention & control)
• Cyclophosphamide (adverse effects)
• Cytokines (blood)
• Glutathione (blood, metabolism)
• Hesperidin (pharmacology, therapeutic use)
• Inflammation (metabolism, prevention & control)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, metabolism)
• Male
• Nitric Oxide (blood)
• Oxidative Stress (drug effects)
• PPAR gamma (metabolism)
• Rats, Wistar
• Transaminases (blood)
• Up-Regulation