title: Crocin attenuates cisplatin-induced liver injury in the mice.
abstract: Cisplatin (CDDP) is one of the most frequently used antitumor agents, but its application is significantly limited by its hepatotoxicity. In the present study, we investigated the effects of crocin against CDDP-induced oxidative stress and apoptosis in the liver of Kunming mice. Crocin was administered to the mice once daily for 7 consecutive days at the doses of 6.25 and 12.5 mg/kg body weight orally. On day 1, a single intraperitoneal injection of CDDP was given at the dose of 10 mg/kg body weight. Crocin treatment significantly improved CDDP-induced hepatic damage as indicated by serum aspartate aminotransferase and alanine aminotransferase levels. Crocin relieved CDDP-induced oxidative stress by reducing malondialdehyde level and recovering the levels of glutathione and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In addition, liver histopathology indicated that crocin alleviated CDDP-induced focal necrosis. Immunohistochemical staining and Western blot analysis showed that crocin significantly decreased the levels of phospho-p38 mitogen-activated protein kinase (MAPK), tumor protein 53 (p53), and cleaved caspase-3. Taken together, our data suggest that crocin provides protective effects against CDDP-induced hepatoxicity by attenuating oxidative stress and inhibiting the activation of p38 MAPK, p53, and caspase-3.
authors.affiliation: Department of Pediatric Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pediatric Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pediatric Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, People's Republic of China.
authors.forename: L-Z
authors.initials: LZ
authors.lastname: Wang
authors.affiliation: Department of Pediatric Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, People's Republic of China xiufangsunqd@163.com.
authors.forename: L-R
authors.initials: LR
authors.lastname: Sun
authors.affiliation: Department of Pediatric Surgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002945:Cisplatin; D019610:Cytoprotection; D004195:Disease Models, Animal; D004789:Enzyme Activation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D061945:Caspase Inhibitors; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D002338:Carotenoids; C029036:crocin; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D002945:Cisplatin
keywords: Crocin; apoptosis; cisplatin; hepatoxicity; oxidative stress; p38 MAPK