Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):10155-10174. doi: 10.1007/s00210-024-03259-5. Epub 2024 Jul 12.
Colistin, a multidrug-resistant gram-negative bacterial infection medication, has been associated with renal impairment and failure. Trans-sodium crocetinate (TSC), a saffron-derived chemical recognized for its antioxidant and nephroprotective properties, was studied in this study to determine its potential to alleviate the nephrotoxic effects of colistin. Forty-two male Wistar rats were randomly classified into seven groups (n = 6): (1) control (normal saline, 12 days, i.p.), (2) colistin (22 mg/kg, 7 days, i.p.), (3-5) colistin + TSC (25, 50, and 100 mg/kg, 12 days, i.p., starting from 5 days before colistin), (6) TSC (100 mg/kg, 12 days, i.p.), (7) colistin + vitamin E (100 IU/kg, 12 days, i.p). On day 13, the rats were euthanized and the serum content of creatinine, BUN, Na, and K, as well as oxidative stress (GSH, MDA, SOD, CAT), inflammatory (IL-1β), apoptotic (Bax, Bcl-2, caspase-3, 8, 9), and autophagy (Beclin-1, LC3) markers, NGAL, and histopathological changes in the kidney were measured. Colistin significantly increased serum creatinine, BUN, MDA, IL-1β, caspase-3,8,9, Bax, Beclin-1, LC3, and NGAL levels in kidney tissue. It also caused inflammation, focal necrosis of tubular epithelial cells, protein cast, and acute tubular necrosis. Furthermore, colistin decreased SOD, CAT, GSH, and Bcl-2 levels. TSC and vitamin E administration along with colistin restored most of the alterations induced by colistin. Overall, it could be concluded that colistin induces oxidative stress, inflammation, autophagy, and apoptosis, which can cause kidney injury. However, TSC can also be used as a therapeutic agent to reduce injuries caused by colistin.
黏菌素是一种治疗多重耐药革兰氏阴性菌感染的药物，但会引起肾损伤和衰竭。西红花衍生的化学物质trans-sodium crocetinate（TSC）具有抗氧化和肾保护作用，本研究旨在探讨其是否能减轻黏菌素的肾毒性。将 42 只雄性 Wistar 大鼠随机分为 7 组（n = 6）：（1）对照组（生理盐水，12 天，腹腔注射）；（2）黏菌素组（22mg/kg，7 天，腹腔注射）；（3-5）黏菌素+TSC 组（25、50 和 100mg/kg，12 天，腹腔注射，从黏菌素前 5 天开始）；（6）TSC 组（100mg/kg，12 天，腹腔注射）；（7）黏菌素+维生素 E 组（100IU/kg，12 天，腹腔注射）。第 13 天处死大鼠，检测血清肌酐、BUN、Na+和 K+、氧化应激（GSH、MDA、SOD、CAT）、炎症（IL-1β）、凋亡（Bax、Bcl-2、caspase-3、8、9）和自噬（Beclin-1、LC3）标志物、NGAL 和肾组织的病理变化。黏菌素显著增加了血清肌酐、BUN、MDA、IL-1β、caspase-3、8、9、Bax、Beclin-1、LC3 和 NGAL 水平，同时引起了炎症、肾小管上皮细胞局灶性坏死、蛋白管型和急性肾小管坏死。此外，黏菌素还降低了 SOD、CAT、GSH 和 Bcl-2 水平。黏菌素联合 TSC 和维生素 E 治疗可恢复黏菌素引起的大部分改变。总之，黏菌素可诱导氧化应激、炎症、自噬和凋亡，从而导致肾损伤；而 TSC 可能作为一种治疗药物，减轻黏菌素引起的损伤。
