Artemether ameliorates kidney injury by restoring redox imbalance and improving mitochondrial function in Adriamycin nephropathy in mice.

Abstract

The kidney is a high-energy demand organ rich in mitochondria especially renal tubular cells. Emerging evidence suggests that mitochondrial dysfunction, redox imbalance and kidney injury are interconnected. Artemether has biological effects by targeting mitochondria and exhibits potential therapeutic value for kidney disease. However, the underlying molecular mechanisms have not been fully elucidated. This study was performed to determine the effects of artemether on Adriamycin-induced nephropathy and the potential mechanisms were also investigated. In vivo, an Adriamycin nephropathy mouse model was established, and mice were treated with or without artemether for 2 weeks. In vitro, NRK-52E cells were stimulated with TGF-β1 and treated with or without artemether for 24 h. Then renal damage and cell changes were evaluated. The results demonstrated that artemether reduced urinary protein excretion, recovered podocyte alterations, attenuated pathological changes and alleviated renal tubular injury. Artemether also downregulated TGF-β1 mRNA expression levels, inhibited tubular proliferation, restored tubular cell phenotypes and suppressed proliferation-related signalling pathways. In addition, artemether restored renal redox imbalance, increased mtDNA copy number and improved mitochondrial function. In summary, we provided initial evidence that artemether ameliorates kidney injury by restoring redox imbalance and improving mitochondrial function in Adriamycin nephropathy in mice. Artemether may be a promising agent for the treatment kidney disease.

• Authors: Pengxun Han, Yuchun Cai, Yao Wang, Wenci Weng, Yinghui Chen, Menghua Wang, Hongyue Zhan, Xuewen Yu, Taifen Wang, Mumin Shao, Huili Sun
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 1266 (01 14 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 33446820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Doxorubicin
• Artemether

Topics

• Animals
• Antimalarials (therapeutic use)
• Artemether (therapeutic use)
• Doxorubicin
• Kidney (drug effects, metabolism, pathology)
• Kidney Diseases (drug therapy, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mitochondria (drug effects, metabolism, pathology)
• Oxidation-Reduction (drug effects)
• Podocytes (drug effects, metabolism, pathology)