Yunfeng ZhaoLi Ming WangLuksana ChaiswingHsiu Chuan YenTerry D. OberleyYu Chin LienShu Mei LinMark P. MattsonDaret St. ClairUniversity of Kentucky College of MedicineUniversity of Wisconsin MadisonMahidol UniversityNational Institute on AgingWake Forest UniversityChang Gung University2018-08-202018-08-202006-04-01Free Radical Biology and Medicine. Vol.40, No.7 (2006), 1234-1241089158492-s2.0-33644922338https://repository.li.mahidol.ac.th/handle/123456789/23061Tamoxifen is the most commonly used antiestrogen for the treatment of breast cancer. Several clinical trials demonstrate that tamoxifen reduces the risk of heart disease and osteoporosis. However, the mechanism by which tamoxifen causes cardioprotection is unclear. Because increased levels of tumor necrosis factor α (TNFα) in tissue and/or plasma have been observed in virtually all forms of cardiac injury, we investigated whether tamoxifen prevents cardiac injury in a murine model of acute TNFα challenge. Five- to six-week-old female mice were injected (ip) with tamoxifen at 0.25 mg/kg daily for 3 or 7 days before receiving an injection of TNFα. Ultrastructural examination of cardiac tissues revealed remarkable protection against TNFα-induced mitochondrial damage in tamoxifen pretreated mice. Tamoxifen treatment significantly improved the mitochondrial respiratory function and enhanced superoxide-scavenging activity of mitochondria. These findings reveal a novel mitochondria-mediated mechanism by which tamoxifen exerts its cardiac protection effect against acute TNFα-induced heart injury. © 2005 Elsevier Inc. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1016/j.freeradbiomed.2005.11.009