Asiwe Jerome Ndudi, Yovwin Godwin D, Alawode Mercy Oluwalani, Isola Theodora, Umukoro Emuesiri Kohworho, Igbokwe Vincent Ugochukwu, Asiwe Nicholas
Department of Physiology, Delta State University, Abraka, Nigeria.
Department of Family Medicine, Delta State University, Abraka, Nigeria.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5811-5822. doi: 10.1007/s00210-024-03650-2. Epub 2024 Nov 30.
A wide range of clinical applications are reported for doxorubicin (DOX), yet both people and research animals experience substantial tissue damage. However, the protective mechanism of lutein, a natural carotenoid against doxorubicin associated liver toxicity has not been fully studied. Therefore, the aim of this study is to investigate the protective mechanism of lutein in doxorubicin-induced liver damage. Twenty male Wistar rats were randomly assigned to four groups and treated as follows: group 1 was administered 10-ml/kg body weight of normal saline intraperitoneally for a duration of 28 days. Group 2 was administered doxorubicin (15-mg/kg body weight) intraperitoneally for 3 days in a row. Group 3 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28 days, and group 4 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28 days with last 3 days in a row (days 26, 27, and 28) of doxorubicin injection (15-mg/kg body weight). Our results showed that lutein reduced levels of AST, ALT, ALP, LDH, MDA, nitrite, beclin-1, caspase-3, IL-6 as well as TNF-α against the increase caused by doxorubicin. GSH, SOD, GST, catalase, mTOR as well as Bcl-2 were markedly increased by lutein against the harmful effect of doxorubicin. Moreso, lutein restored normal histoarchitecture as well as reduced fibrosis. In conclusion, lutein protection against doxorubicin-induced liver damage in male Wistar rat is associated with inhibition of oxidative stress, pro-inflammatory reactions, and modulation of Beclin-1/mTOR activities.
阿霉素(DOX)有广泛的临床应用报道,但人类和实验动物都会出现严重的组织损伤。然而,天然类胡萝卜素叶黄素对阿霉素相关肝毒性的保护机制尚未得到充分研究。因此,本研究的目的是探讨叶黄素在阿霉素诱导的肝损伤中的保护机制。将20只雄性Wistar大鼠随机分为四组并进行如下处理:第1组腹腔注射10 ml/kg体重的生理盐水,持续28天。第2组连续3天腹腔注射阿霉素(15 mg/kg体重)。第3组每天腹腔注射叶黄素(40 mg/kg体重),持续28天,第4组每天腹腔注射叶黄素(40 mg/kg体重),持续28天,并在最后3天(第26、27和28天)连续腹腔注射阿霉素(15 mg/kg体重)。我们的结果表明,叶黄素降低了阿霉素引起的AST、ALT、ALP、LDH、MDA、亚硝酸盐、beclin-1、caspase-3、IL-6以及TNF-α的水平升高。叶黄素显著提高了GSH、SOD、GST、过氧化氢酶、mTOR以及Bcl-2的水平,对抗阿霉素的有害作用。此外,叶黄素恢复了正常的组织结构并减少了纤维化。总之,叶黄素对雄性Wistar大鼠阿霉素诱导的肝损伤的保护作用与抑制氧化应激、促炎反应以及调节Beclin-1/mTOR活性有关。