Department of Dental Basic Sciences, Faculty of Dentistry, Applied Science Private University, Amman, Jordan.
Histology Department, Damietta Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
PeerJ. 2024 Jul 22;12:e17687. doi: 10.7717/peerj.17687. eCollection 2024.
Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol.
Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done.
Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues.
Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats anti-inflammatory and oxidative stress-apoptotic pathways.
顺铂(CIS)是一种广谱抗癌药物,对恶性或正常细胞均具有细胞毒性作用。我们旨在评估 CIS 对大鼠的肝毒性及其与姜黄素或白藜芦醇联合应用的改善作用。
将 40 只成年雄性大鼠分为四组,每组各 10 只:(对照组):大鼠连续 28 天每天腹腔内给予生理盐水(0.9%)一次;(顺铂组):大鼠连续 3 天每天腹腔内给予顺铂(3.3mg/kg)单次剂量后,连续 28 天每天给予生理盐水(0.9%)口服剂量;(CIS 加姜黄素/白藜芦醇组):大鼠连续 3 天每天给予相同剂量的顺铂(3.3mg/kg),随后连续 28 天每天口服姜黄素/白藜芦醇溶液(20mg/kg)或(10mg/kg)。进行了不同的实验室检查(ALT、AST、ALP、胆红素、氧化应激标志物)和光镜检查。
CIS 的给药导致大鼠肝毒性,表现为肝酶升高、氧化应激标志物增加;退行性和凋亡变化,CIS 与姜黄素或白藜芦醇联合应用可通过改善微观结构变化、降低肝酶活性、降低氧化应激标志物、改善肝组织的退行性和凋亡变化来改善肝毒性。
顺铂治疗时联合使用姜黄素或白藜芦醇可减轻顺铂引起的大鼠肝毒性,其机制可能与抗炎和氧化应激-凋亡途径有关。