Cecen E, Dost T, Culhaci N, Karul A, Ergur B, Birincioglu M
Department of Pediatric Oncology, Adnan Menderes University, School of Medicine, Aydin, Turkey.
Asian Pac J Cancer Prev. 2011;12(10):2697-704.
The aim of the present study was to investigate the effect of silymarin on doxorubicin-induced toxicity to the rat kidney, heart, and liver.
A single dose of 10 mg/kg doxorubicin was injected intraperitoneally (ip) in the doxorubicin group. The silymarin group received silymarin (100mg/kg) every other day. In the doxorubicin + silymarin group, silymarin was injected ip at 100 mg/kg dose for 5 days before doxorubicin administration (10 mg/kg, single ip injection) and then continued daily thereafter until euthanization. On the seventh day after doxorubicin injection, eight animals from each group were decapitated and liver and heart samples were obtained. The remaining eight animals of each group continued to receive silymarin every other day, till euthanized on the twenty first day. Serum was separated for determination of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO), creatinine, urea, AST, ALT, lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) activities. Histopathological and electron microscopic examinations of heart, kidney and liver sections were also performed.
Doxorubicin caused a significant increase in serum NO levels compared to controls. Silymarin pretreatment group lowered these. Histopathological and electron microscopic examinations of kidney, heart, and liver sections showed doxorubicin to cause myocardial and renal injury which was levv evident in silymarin treated rats.
CONCLUSION(S): Results of the present study indicate that silymarin significantly protected doxorubicin-induced toxicities to the rat kidney, heart, and liver, thus suggesting its administration as a supportive care agent during anti-cancer treatment featuring doxorubicin.
本研究旨在探讨水飞蓟素对阿霉素诱导的大鼠肾脏、心脏和肝脏毒性的影响。
阿霉素组腹腔注射单次剂量10mg/kg阿霉素。水飞蓟素组每隔一天给予水飞蓟素(100mg/kg)。在阿霉素+水飞蓟素组中,在给予阿霉素(10mg/kg,单次腹腔注射)前5天,以100mg/kg剂量腹腔注射水飞蓟素,然后此后每天持续给药直至处死。在注射阿霉素后第7天,每组处死8只动物,获取肝脏和心脏样本。每组其余8只动物继续每隔一天接受水飞蓟素给药,直至在第21天处死。分离血清以测定超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)、过氧化氢酶(CAT)、丙二醛(MDA)、一氧化氮(NO)、肌酐、尿素、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)和肌酸磷酸激酶(CPK)活性。还对心脏、肾脏和肝脏切片进行了组织病理学和电子显微镜检查。
与对照组相比,阿霉素导致血清NO水平显著升高。水飞蓟素预处理组降低了这些水平。肾脏、心脏和肝脏切片的组织病理学和电子显微镜检查显示,阿霉素导致心肌和肾脏损伤,在水飞蓟素治疗的大鼠中这种损伤不太明显。
本研究结果表明,水飞蓟素显著保护了阿霉素诱导的大鼠肾脏、心脏和肝脏毒性,因此表明在以阿霉素为特征的抗癌治疗期间,将其作为支持性护理药物给药。