Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Life Sci. 2019 Aug 15;231:116573. doi: 10.1016/j.lfs.2019.116573. Epub 2019 Jun 14.
Hepatotoxicity is a common side effect encountered with tamoxifen (TAM) administration. Due to the great value of TAM in breast cancer treatment, hepato-protection is seriously recommended.
The present study investigated the hepato-protective effect of celecoxib (CX) against TAM-induced hepatotoxicity in rats.
Female rats were injected with TAM (45 mg/kg, i.p.) for 7 days and given CX (15 mg/kg, orally) 7 days before TAM injection, then continued for the following 7 days.
Administration of CX for 14 days conferred significant hepatoprotection against TAM-induced hepatotoxicity indexed by decreased liver/body weight ratio, boosted cytoprotection and substantial reduction in serum LDH activity besides functional hepatic improvement; marked decrease in ALT, AST and ALP with significant elevation in serum albumin. Oxidant/antioxidants hemostasis was improved upon CX treatment with profound decrease in hepatic MDA content and elevation of GSH and SOD levels. Furthermore, hepatic content of NO decreased along with significant decrease in ASK-1, JNK and Bax levels as well as TNFα and caspase3 expression. Finally, CX administration resulted in obvious diminution of TAM-induced necrotic and apoptotic alterations.
Celecoxib might be used in combination with TAM in treatment protocol of breast to prevent liver injury induced by TAM and further clinical studies might be needed to approve this notion.
肝毒性是他莫昔芬（TAM）给药的常见副作用。由于 TAM 在乳腺癌治疗中的重要价值，严重建议进行肝保护。
本研究旨在研究塞来昔布（CX）对 TAM 诱导的大鼠肝毒性的肝保护作用。
雌性大鼠连续 7 天腹腔注射 TAM（45mg/kg），并在 TAM 注射前 7 天开始口服 CX（15mg/kg），然后继续注射 7 天。
CX 给药 14 天可显著减轻 TAM 诱导的肝毒性，表现为肝/体重比降低、细胞保护作用增强、血清 LDH 活性显著降低以及肝功能改善；ALT、AST 和 ALP 显著降低，血清白蛋白显著升高。CX 治疗可改善氧化应激/抗氧化剂平衡，肝 MDA 含量显著降低，GSH 和 SOD 水平升高。此外，肝 NO 含量降低，ASK-1、JNK 和 Bax 水平以及 TNFα和 caspase3 表达降低。最后，CX 给药可明显减轻 TAM 诱导的坏死和凋亡改变。
塞来昔布可能与 TAM 联合用于乳腺癌的治疗方案中，以预防 TAM 引起的肝损伤，可能需要进一步的临床研究来证实这一观点。
