The combination of dapagliflozin and statins ameliorates renal injury through attenuating the activation of inflammasome-mediated autophagy in insulin-resistant rats
Issued Date
2022-04-01
Resource Type
ISSN
10956670
eISSN
10990461
Scopus ID
2-s2.0-85121657814
Pubmed ID
34939712
Journal Title
Journal of Biochemical and Molecular Toxicology
Volume
36
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Biochemical and Molecular Toxicology Vol.36 No.4 (2022)
Suggested Citation
Thongnak L., Pengrattanachot N., Promsan S., Phengpol N., Sutthasupha P., Chatsudthipong V., Lungkaphin A. The combination of dapagliflozin and statins ameliorates renal injury through attenuating the activation of inflammasome-mediated autophagy in insulin-resistant rats. Journal of Biochemical and Molecular Toxicology Vol.36 No.4 (2022). doi:10.1002/jbt.22978 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83792
Title
The combination of dapagliflozin and statins ameliorates renal injury through attenuating the activation of inflammasome-mediated autophagy in insulin-resistant rats
Author's Affiliation
Other Contributor(s)
Abstract
Long-term use of a high-fat diet with high-fructose (HFF) intake could promote insulin resistance and induce lipid accumulation leading to kidney injury possibly via impairment of the autophagy process and enhancement of the inflammasome pathway. We investigated whether dapagliflozin as a monotherapy or combined with atorvastatin could restore kidney autophagy impairment and reduce inflammasome activation associated with kidney injury induced by HFF consumption. Male Wistar rats were given an HFF for 16 weeks and then treated with dapagliflozin with or without atorvastatin for 4 weeks. Impaired glucose tolerance, dyslipidemia, renal lipid accumulation along with impaired renal autophagy and activated inflammasome pathway promoted renal injury were exhibited in HFF rats. Dapagliflozin with or without atorvastatin treatment could partially restore disrupted metabolic parameters and reduce kidney injury. In particular, the combination treatment group showed significant amelioration of inflammasome activation and autophagy impairment. In conclusion, the combination therapy of dapagliflozin and atorvastatin has a positive effect on renal injury associated with autophagy and inflammasome activation induced by HFF in insulin-resistant rats. This study is the first report demonstrating the underlying mechanism associated with a combination treatment of dapagliflozin and atorvastatin on autophagy and inflammasome pathways in an insulin-resistant condition. Therefore, dapagliflozin in combination with atorvastatin may be a further preventive or therapeutic strategy for chronic kidney disease in an insulin-resistant or diabetic condition.