Lactobacillus rhamnosus GKLC1 ameliorates cisplatin-induced chronic nephrotoxicity by inhibiting cell inflammation and apoptosis.

Abstract

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.

• Authors: You-Shan Tsai, Yen-Po Chen, Shih-Wei Lin, Yen-Lien Chen, Chin-Chu Chen, Guan-Jhong Huang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 147 Pg. 112701 (Mar 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 35131657 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antineoplastic Agents
• Inflammation Mediators
• bcl-2-Associated X Protein
• Creatinine
• Mitogen-Activated Protein Kinases
• Caspase 3
• Cisplatin

Topics

• Acute Kidney Injury (chemically induced, pathology)
• Animals
• Antineoplastic Agents (adverse effects)
• Apoptosis (drug effects)
• Blood Urea Nitrogen
• Caspase 3 (drug effects)
• Cisplatin (adverse effects)
• Creatinine (blood)
• Dose-Response Relationship, Drug
• Inflammation (pathology)
• Inflammation Mediators (metabolism)
• Lacticaseibacillus rhamnosus
• Male
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (drug effects)
• Probiotics (administration & dosage, pharmacology)
• Rats
• Signal Transduction (drug effects)
• bcl-2-Associated X Protein (drug effects)