- CZ slows the progression of the renal fibrosis associated with type 2 diabetes in KKAy mice
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Dohyun Lee,Jongsu Jeon,Seoyeong Baek,Onyu Park,Myoung-Sool Do,Seung hee Yang,Hoe-Yune Jung
2022 ; 2022(1):
- 논문분류 :
- 춘계학술대회 초록집
Objectives: Current treatments for diabetic nephropathy (DN) aim to slow the progression of kidney damage and control related complications, but new drugs with fewer side effects and novel mode of action are still needed. The supplementation improved the effectiveness of OHA(oral hypoglycemic agents) in combination with zinc in DN patients. In this study, we present another novel therapeutic agent for the treatment of DN that meets current needs.
Methods: Pathological changes in the glomeruli of KK-Ay mice are known to be consistent with those observed in the early stages of human DN. Therefore, we investigated the efficacy of CZ on DN using KK-Ay mice and compared its efficacy with dapagliflozin. 6-week-old KK-Ay mice were administered with CZ or dapagliflozin for 10 weeks. Then, glomerular filtration rate (GFR) was measured using FITC-Sinistrin with a transdermal GFR measurement monitor and urine pathological markers such as albumin and creatinine were analyzed. In addition, the expression of genes and proteins associated with renal inflammation, fibrosis, and apoptosis was investigated. Moreover, we examined the CZ’s possible effects on podocyte damage and loss using transmission electron microscopy
Results: As a result of the transdermal GFR measurement, CZ administration significantly increased the GFR value compared to the control group to a level similar to that of dapagliflozin. CZ administration also significantly reduced the urine albumin-to-creatinine ratio (ACR) by half compared to the control group. In the kidney, the expression of several inflammatory cytokines, apoptotic genes and renal fibrotic markers were dramatically decreased by CZ administration. In addition, CZ limits podocyte dysfunction and loss in mice with proteinuric nephropathy.
Conclusions: These results demonstrate that CZ not only improves hyperglycemia but also slows the progression of diabetes-associated glomerulosclerosis by reducing renal damage such as inflammation and apoptosis and suppressing the progression of renal fibrosis.