Daily sesame oil supplementation mitigates ketoconazole-induced oxidative stress-mediated apoptosis and hepatic injury.
Ketoconazole (KCZ) is the most commonly used systemic antifungal drug. However, long-term treatment of KCZ induces hepatic injury. Oxidative stress is involved in KCZ-induced hepatic injury. Oxidative stress plays an important role in apoptosis-associated hepatic damage. Sesame oil is rich in potent antioxidants and antifungal constituents. It attenuates hepatic injury by inhibiting oxidative stress. Thus, sesame oil may protect against KCZ-induced oxidative stress, apoptosis and hepatic damage. The aim of the present study was to investigate the protective effect of sesame oil as a nutritional supplement on KCZ-induced hepatic injury in mice. KCZ (300 mg/kg/day) was administered by gastric intubation; 30 min later, sesame oil (0, 0.0625, 0.125, 0.25 or 0.5 ml/kg/day; p.o.) was administered to mice for 14 days. Blood and liver tissue were collected. Hepatic injury was evaluated by serum biochemistry and histology. Oxidative stress was evaluated by myeloperoxidase activity, p47-phox, reactive oxygen species generation, lipid peroxidation and glutathione level. Apoptosis was evaluated by p53, caspase-3, Bcl-2, Bax and Cyto-C expression. Osteopontin was measured to assess liver healing. Sesame oil attenuated hepatic injury; it also decreased oxidative stress and apoptosis in KCZ-treated mice. Sesame oil may be used as a nutritional supplement with existing antifungal therapies to neutralize the adverse hepatotoxic nature of antifungal drugs by attenuating hepatic apoptosis through redox system to protect and heal liver injury in KCZ-treated mice.
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
Srinivasan
S
Periasamy
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
Chuan-Teng
CT
Liu
Department of Food and Beverage Services, Tainan University of Technology, Tainan 71002, Taiwan.
Se-Ping
SP
Chien
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
Ying-Chien
YC
Chen
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan. Electronic address: myliu@mail.ncku.edu.tw.
Ming-Yie
MY
Liu
D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects* / Q000737:chemistry; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007654:Ketoconazole / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D009336:Necrosis; D018375:Neutrophil Activation / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012715:Sesame Oil / Q000008:administration & dosage / Q000627:therapeutic use*
D000935:Antifungal Agents; D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species; C506896:Spp1 protein, mouse; D053495:Osteopontin; D012715:Sesame Oil; D005978:Glutathione; D007654:Ketoconazole
Apoptosis; Hepatic injury; Ketoconazole; Oxidative stress; Sesame Oil