Abstract：
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.
摘要：
粘菌素,耐多药革兰氏阴性菌感染药物，与肾功能损害和衰竭有关。反式-克罗西酸钠(TSC)，一种藏红花衍生的化学物质，因其抗氧化和肾脏保护特性而被认可，在这项研究中进行了研究，以确定其减轻粘菌素肾毒性作用的潜力。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,i.p.),（2）粘菌素（22mg/kg，7天,i.p.),（3-5）粘菌素+TSC（25、50和100mg/kg，12天,i.p.,从粘菌素之前5天开始)，（6）TSC（100mg/kg，12天,i.p.),（7）粘菌素+维生素E（100IU/kg，12天,i.p).在第13天，对大鼠实施安乐死，血清肌酐含量，BUN,Na+,K+,以及氧化应激(GSH，MDA,SOD,CAT),炎症（IL-1β），凋亡（Bax，Bcl-2,caspase-3,8,9),和自噬（Beclin-1，LC3）标记，NGAL,并测量了肾脏的组织病理学变化。粘菌素显著增加血清肌酐，BUN,MDA,IL-1β,caspase-3,8,9,Bax,肾组织中Beclin-1、LC3和NGAL水平。它还引起炎症，肾小管上皮细胞局灶性坏死,蛋白质铸件，和急性肾小管坏死.此外，粘菌素降低SOD，CAT,GSH,Bcl-2水平。TSC和维生素E与粘菌素一起施用恢复了粘菌素诱导的大部分改变。总的来说,可以得出结论，粘菌素诱导氧化应激，炎症,自噬,和细胞凋亡，会导致肾损伤.然而,TSC还可以用作治疗剂以减少由粘菌素引起的损伤。
