Pengxun Han1, Hongyue Zhan1, Mumin Shao2, Wenjing Wang1, Gaofeng Song1, Xuewen Yu2, Chunlei Zhang3, Na Ge1, Tiegang Yi1, Shunmin Li4, Huili Sun5. 1. Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China. 2. Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China. 3. Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China. 4. Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China. Electronic address: shunminli@126.com. 5. Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China. Electronic address: sunhuili2011@126.com.
Abstract
AIMS: Early diabetic kidney disease (DKD) is characterized by renal hypertrophy and albuminuria. The mTOR signal pathway is closely related to DKD. This study was performed to determine the renal protection of niclosamide ethanolamine salt (NEN) which was identified as mTOR inhibitor. METHODS: Type 2 diabetes (T2D) db/db mice were used and divided into db/db and db/db + NEN groups. Lean wild type mice served as T2D-control. NEN treatment lasted for 12 weeks. The kidney morphological changes, urine indices, blood glucose and metabolic symptoms were evaluated. In addition, the effects of NEN on kidney mitochondria and mTOR/4E-BP pathway were also measured. RESULTS: NEN could prevent diabetic kidney hypertrophy and alleviate glomerular mesangial expansion, attenuate GBM and TBM thickening in db/db mice. It also restored podocyte dysfunction, reduced urinary albumin, NAG, NGAL, and TGF-β1 excretion. Specifically, it could uncouple kidney mitochondria and significantly inhibit renal cortical activation of mTOR/4E-BP1 pathway. CONCLUSIONS: This study demonstrated that NEN could improve kidney injury in db/db mice and has the potential to translate to future clinical studies.
AIMS: Early diabetic kidney disease (DKD) is characterized by renal hypertrophy and albuminuria. The mTOR signal pathway is closely related to DKD. This study was performed to determine the renal protection of niclosamide ethanolamine salt (NEN) which was identified as mTOR inhibitor. METHODS:Type 2 diabetes (T2D) db/db mice were used and divided into db/db and db/db + NEN groups. Lean wild type mice served as T2D-control. NEN treatment lasted for 12 weeks. The kidney morphological changes, urine indices, blood glucose and metabolic symptoms were evaluated. In addition, the effects of NEN on kidney mitochondria and mTOR/4E-BP pathway were also measured. RESULTS:NEN could prevent diabetic kidney hypertrophy and alleviate glomerular mesangial expansion, attenuate GBM and TBM thickening in db/db mice. It also restored podocyte dysfunction, reduced urinary albumin, NAG, NGAL, and TGF-β1 excretion. Specifically, it could uncouple kidney mitochondria and significantly inhibit renal cortical activation of mTOR/4E-BP1 pathway. CONCLUSIONS: This study demonstrated that NEN could improve kidney injury in db/db mice and has the potential to translate to future clinical studies.
Authors: Abdelhalim B Mahmoud; Shereen Abd Algaffar; Wendy van de Sande; Sami Khalid; Marcel Kaiser; Pascal Mäser Journal: Molecules Date: 2021-06-30 Impact factor: 4.411