Publication: Effects of dapagliflozin and statins attenuate renal injury and liver steatosis in high-fat/high-fructose diet-induced insulin resistant rats
Issued Date
2020-06-01
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ISSN
10960333
0041008X
0041008X
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2-s2.0-85082725451
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Mahidol University
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SCOPUS
Bibliographic Citation
Toxicology and Applied Pharmacology. Vol.396, (2020)
Suggested Citation
Laongdao Thongnak, Varanuj Chatsudthipong, Aphisek Kongkaew, Anusorn Lungkaphin Effects of dapagliflozin and statins attenuate renal injury and liver steatosis in high-fat/high-fructose diet-induced insulin resistant rats. Toxicology and Applied Pharmacology. Vol.396, (2020). doi:10.1016/j.taap.2020.114997 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/54702
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Title
Effects of dapagliflozin and statins attenuate renal injury and liver steatosis in high-fat/high-fructose diet-induced insulin resistant rats
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Abstract
© 2020 High-fat high-fructose diet (HFF) in obesity can induce dyslipidemia and lipid accumulation both in kidney and liver which related to insulin resistance and lipotoxicity-induced cellular damage. We investigated whether dapagliflozin with or without atorvastatin could improve lipid accumulation-induced kidney and liver injury in HFF-induced insulin resistant rats. Male Wistar rats were fed with HFF for 16 weeks and then received drug treatments for 4 weeks; vehicle, dapagliflozin, atorvastatin and dapagliflozin plus atorvastatin treatment groups. HFF rats demonstrated insulin resistance, dyslipidemia, liver injury and renal dysfunction associated with impaired renal lipid metabolism and lipid accumulation. Dapagliflozin and combination treatment could improve HFF-induced insulin resistance, lipogenesis and lipotoxicity-related renal oxidative stress, inflammation, fibrosis and apoptosis leading to kidney dysfunction recovery. Liver injury-associated inflammation was also improved by these two regimens. Notably, the reduced lipid accumulation in liver and kidney that linked to an improvement of lipid oxidation was prominent in the combination treatment. Therefore, dapagliflozin combined with atorvastatin treatment exert the beneficial effects on lipid metabolism and lipotoxicity in liver and kidney injury via the attenuation of oxidative stress, fibrosis and apoptosis in insulin resistant model.