Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines

• Published in: Journal of pharmacy and pharmacology 2013-04, Vol.65 (4), p.604-614
• Main Authors: Jnaneshwari, Sadashivaiah, Hemshekhar, Mahadevappa, Santhosh, Martin Sebastin, Sunitha, Kabburahalli, Thushara, Rammohan, Thirunavukkarasu, Chinnasamy, Kemparaju, Kempaiah, Girish, Kesturu Subbaiah
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antineoplastic Agents, Alkylating - adverse effects; Antineoplastic Agents, Alkylating - antagonists & inhibitors; Antioxidants; Antioxidants - therapeutic use; Biomarkers - blood; Biomarkers - metabolism; Carotenoids - therapeutic use; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; crocin; cyclophosphamide; Cyclophosphamide - adverse effects; Cyclophosphamide - antagonists & inhibitors; Cytokines - blood; Enzymes; Food Coloring Agents - therapeutic use; hepatotoxicity; Hydrogen Peroxide - metabolism; inflammation; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - immunology; Liver - metabolism; Liver - pathology; oxidative stress; Oxidative Stress - drug effects; Oxidoreductases - metabolism; Protein Carbonylation - drug effects; Protein Processing, Post-Translational - drug effects; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Rodents; Toxicity
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12016

Objectives This study investigated the protective efficacy of crocin against hepatotoxicity induced by cyclophosphamide (CP) in Wistar rats. Methods The experimental rats were treated with crocin orally at a dose of 10 mg/kg for 6 consecutive days after the administration of a single intraperitoneal dose of CP (150 mg/kg). The ameliorative effect of crocin on organ toxicity was studied by evaluating oxidative stress enzymes, inflammatory cytokines and histological sections. Key Findings A single intraperitoneal CP injection significantly elevated endogenous reactive oxygen species and oxidation of lipids and proteins, which are the hallmarks of oxidative damage in liver and serum. In consequence, the primary defensive reduced glutathione, total thiol and antioxidant enzymes such as superoxide dismutase, catalase, glutathione‐S‐transferase and glutathione peroxidase, were significantly reduced. In addition, liver and serum aspartate aminotransferase and alanine aminotransferase along with acid and alkaline phosphatase were considerably increased. Oral administration of crocin significantly rejuvenated all the above altered markers to almost normal state. The protective efficacy of crocin was further supported by the histological assessment and restoration of CP‐induced inflammatory cytokines and enzyme levels compared with the control drug. Conclusion The results obtained suggest the protective nature of crocin against CP‐induced oxidative damage/inflammation and organ toxicity.