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

You-Shan Tsai; Yen-Po Chen; Shih-Wei Lin; Yen-Lien Chen; Chin-Chu Chen; Guan-Jhong Huang

doi:10.1016/j.biopha.2022.112701

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

Biomed Pharmacother. 2022 Mar:147:112701. doi: 10.1016/j.biopha.2022.112701. Epub 2022 Feb 4.

Authors

You-Shan Tsai¹, Yen-Po Chen¹, Shih-Wei Lin², Yen-Lien Chen¹, Chin-Chu Chen³, Guan-Jhong Huang⁴

Affiliations

¹ Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325002, Taiwan.
² Department of Food Science and Biotechnology, National Chung Hsing University, Taichung City 402204, Taiwan.
³ Institute of Food Science and Technology, National Taiwan University, Taipei City 106319, Taiwan; Department of Food Science, Nutrition and Nutraceutical Biotechnology, Shih Chien University, Taipei City 104336, Taiwan; Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City 320314, Taiwan. Electronic address: gkbioeng@grapeking.com.tw.
⁴ Department of Chinese Pharmaceutical Science and Chinese Medicine Recourses, College of Chinese Medicine, China Medical University, Taichung City 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung City 413305, Taiwan. Electronic address: gjhuang@mail.cmu.edu.tw.

PMID: 35131657
DOI: 10.1016/j.biopha.2022.112701

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.

Keywords: Chemotherapeutic drug; Chronic kidney disease (CKD); Gut-kidney axis; Inflammatory; Oxidative stress; Probiotics.

MeSH terms

Acute Kidney Injury / chemically induced*
Acute Kidney Injury / 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
Probiotics / pharmacology*
Rats
Signal Transduction / drug effects
bcl-2-Associated X Protein / drug effects

Substances

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