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.
Background Diabetes-related muscle wasting is one of the devastating complications of diabetes, which is associated with muscle autophagy due to insulin-mediated glucose starvation. However, treatment for diabetes-related muscle wasting is limited. Our previous study already found that niclosamide ethanolamine salt has the therapeutic effects on insulin deficiency of type 1 diabetes mice and muscle wasting induced by doxorubicin. Therefore, we aim to investigate the therapeutic effects of niclosamide ethanolamine salt on diabetes-induced muscle wasting and to explore whether the mechanism is associated with muscle autophagy. Methods Type 1 diabetes mice were induced by intraperitoneal injection of streptozotocin, then were fed with regular diet supplemented with 10 g/kg niclosamide ethanolamine salt. The whole experiment lasted for 8 weeks. At the end of the study, grip strength, weights of tibialis anterior, gastrocnemius, soleus, and extensor digitorum longus muscle were measured. Tibialis anterior muscles stained with PAS were used for evaluating the fiber cross sectional area. Immunofluorescence analysis of myosin heavy chain expression in extensor digitorum longus and soleus muscle was used for determining the composition of the muscle fiber type. Electronic microscopy was applied to observe the autophagy in the atrophied muscle. Serum insulin levels and fasting blood glucose were also measured. Tissues of gastrocnemius muscle were used for detecting the expression of the proteins related to autophagy. Results In this study, we found that niclosamide ethanolamine salt could ameliorate muscle atrophy in the type 1 diabetes mice as well, such as enhancing the declined grip strength, improving limb weight and increasing the numbers of glycolytic muscle fiber. Electron microscopy also confirmed that there did exist abundant autophagic vacuoles in the atrophied muscle of the type 1 diabetes mice. Specifically, niclosamide ethanolamine salt could reduce the over expression of autophagy-related proteins, including p-AMPK (Thr172), FoxO3a, p-ULK1 (Ser555), LC3B II, and p-p38 in gastrocnemius muscle of the type 1 diabetes mice. Conclusion Niclosamide ethanolamine salt could ameliorate muscle wasting. The mechanisms underlying might be associated with inhibition of muscle autophagy.
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