Abstract: SA-PO261
Molecular Mechanisms of Cobalt Chloride in the Treatment of Type 2 Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - 2
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Deng, Tianyu, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Yu, Shiyue, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Chen, Xueqi, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Han, Zhenyuan, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Yan, Dechao, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Liu, Mingda, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
- Wang, Xiaoyan, Nanjing BenQ Medical Center, Nanjing, Jiangsu, China
Background
Down-regulation of heme-oxygenases (HOs) induced by oxidative stress plays an important role in the pathogenesis of type 2 diabetic nephropathy (T2DN). COPP (cobalt chloride), a HO-1 agonist, has been used in experimental DN. To explore the underlying mechanism, caspase3, Gasdermin-E (GSDME), and other factors related to apoptosis and pyroptosis besides ROS-components were observed in the kidneys of type 2 DN mice with and without COPP treatment.
Methods
Male 7-week-old C57BL/6J mice were fed a 60% high-fat diet for 6 weeks, then injected intraperitoneally with STZ(60mg/kg/day) (DN) or vehicle (HFD) for 3 days. COPP at 3mg/kg was given to the STZ mice (DN+COPP) by weekly intraperitoneal injection (10 doses) while the background group (NFD) was given a 10% normal fat diet and vehicle injections until week 16 of the study (n=5-7/group).
Results
Fasting blood glucose levels in DN group(26.2±1.0, mmol/L) were higher than those in NFD(8.0±0.8) and HFD (8.7±0.6) groups but lowered slightly by COPP treatment (22.3±0.9). Serum creatinine (156.6±43.3, mmol/L) was higher than NFD(12.3±0.9) and HFD(21.9±6.1) groups but reversed after COPP treatment (65.8±9.7). Urinary albumin/creatinine exerts similar results in DN group(48.5±3.0, mg/g), NFD(3.0±0.6), HFD(20.7±5.2) groups and DN+COPP group (37.7±5.5). The glomerular basement membrane thickening and podocyte fusion seen in DN group by EM were reversed after COPP treatment. 8-OHdG, an oxidative stress index, increased (163.6±34.5, % of NFD, same as below) in the DN group and decreased after COPP treatment (130.8±22.6). HO-1(302.9±170.3) and PON1(63.0±8.1) was decreased in DN+COPP, after COPP treatment HO-1(701.7±171.1) and PON1(136.4±15.5) were reversed. Similarly, GSDME (139±7.2) and caspase 3(109.7±4.0) increased in DN group, and after COPP treatment GSDME (122.0±4.9) and caspase 3(100.7±2.3) were mitigated. In addition, BAX/Bcl-2, the key factor regulating apoptosis, increased in the DN group (159.0±21.6) and reversed after COPP treatment (94±6.3).
Conclusion
COPP may attenuate renal injury in type 2 diabetic mice by reducing apoptosis and pyroptosis along with its antioxidant effects.
Funding
- Government Support – Non-U.S.