Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325002, Taiwan.
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung City 402204, Taiwan.
Biomed Pharmacother. 2022 Mar;147:112701. doi: 10.1016/j.biopha.2022.112701. Epub 2022 Feb 4.
Sustained usage of the chemotherapeutic drug cisplatin may lead to chronic kidney disease (CKD). Despite cisplatin being toxic to the kidneys, the efficiency of its therapeutic effects cannot be completely replaced with other drugs. Probiotics can produce various strain-specific health-promoting effects and suppress many specific diseases. In this study, we present the alleviation of cisplatin-induced CKD with a probiotic, Lactobacillus rhamnosus GKLC1. Intermittent low doses of cisplatin were given to male CB57BL/6 mice (n = 6), which induced CKD symptoms such as weight loss, lesions in kidney tissue, and increases in blood urea nitrogen (BUN) and creatinine (CRE) in serum. The rats received two weeks of L. rhamnosus GKLC1 orally at doses of 125, 250, and 500 mg/kg B.W./day. After the treatment, significant dose-dependent reductions were observed in the kidney index, histopathological scoring, serum BUN, and CRE. An LLC-PK1 kidney cell assay revealed that L. rhamnosus GKLC1 suppressed the nephrotoxicity of cisplatin by reducing the inflammation via the MAPKs/NF-ĸB/COX-2 pathway, inhibiting apoptosis via the p53/Bax/Caspase-3 pathway, and ameliorating fibrosis via the STAT3 pathway. We conclude that L. rhamnosus GKLC1 could be applied as an agent to ameliorate the development of CKD.
顺铂的持续使用可能导致慢性肾病(CKD)。尽管顺铂对肾脏有毒,但它的治疗效果效率不能完全被其他药物替代。益生菌可以产生各种菌株特异性的促进健康的作用,并抑制许多特定的疾病。在这项研究中,我们提出了使用益生菌鼠李糖乳杆菌 GKLC1 来缓解顺铂诱导的 CKD。间歇性给予低剂量顺铂给雄性 CB57BL/6 小鼠(n=6),诱导 CKD 症状,如体重减轻、肾脏组织损伤以及血清中血尿素氮(BUN)和肌酐(CRE)升高。大鼠每天口服给予 125、250 和 500mg/kg B.W. 的鼠李糖乳杆菌 GKLC1 两周。治疗后,观察到肾指数、组织病理学评分、血清 BUN 和 CRE 显著的剂量依赖性降低。LLC-PK1 肾细胞测定表明,鼠李糖乳杆菌 GKLC1 通过 MAPKs/NF-ĸB/COX-2 通路减少炎症,通过 p53/Bax/Caspase-3 通路抑制细胞凋亡,通过 STAT3 通路改善纤维化,从而抑制顺铂的肾毒性。我们得出结论,鼠李糖乳杆菌 GKLC1 可作为一种改善 CKD 发展的药物。
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