GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats
Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2016-12-01
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| Series: | Kidney & Blood Pressure Research |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/452598 |
| _version_ | 1818162397256351744 |
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| author | Bo Hu Yuhong Wu Jie Liu Xiaohua Shen Fei Tong Guangtao Xu Ruilin Shen |
| author_facet | Bo Hu Yuhong Wu Jie Liu Xiaohua Shen Fei Tong Guangtao Xu Ruilin Shen |
| author_sort | Bo Hu |
| collection | DOAJ |
| description | Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM. |
| first_indexed | 2024-12-11T16:33:01Z |
| format | Article |
| id | doaj.art-30c9973f36594a99add8c685c1ff7c97 |
| institution | Directory Open Access Journal |
| issn | 1420-4096 1423-0143 |
| language | English |
| last_indexed | 2024-12-11T16:33:01Z |
| publishDate | 2016-12-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Kidney & Blood Pressure Research |
| spelling | doaj.art-30c9973f36594a99add8c685c1ff7c972022-12-22T00:58:32ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432016-12-0141693794610.1159/000452598452598GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic RatsBo HuYuhong WuJie LiuXiaohua ShenFei TongGuangtao XuRuilin ShenBackground/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.http://www.karger.com/Article/FullText/452598Diabetes mellitusRenal ischemia/reperfusion injuryGSK-3beta inhibitorNrf2TrxR2 |
| spellingShingle | Bo Hu Yuhong Wu Jie Liu Xiaohua Shen Fei Tong Guangtao Xu Ruilin Shen GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats Kidney & Blood Pressure Research Diabetes mellitus Renal ischemia/reperfusion injury GSK-3beta inhibitor Nrf2 TrxR2 |
| title | GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats |
| title_full | GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats |
| title_fullStr | GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats |
| title_full_unstemmed | GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats |
| title_short | GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats |
| title_sort | gsk 3beta inhibitor induces expression of nrf2 trxr2 signaling pathway to protect against renal ischemia reperfusion injury in diabetic rats |
| topic | Diabetes mellitus Renal ischemia/reperfusion injury GSK-3beta inhibitor Nrf2 TrxR2 |
| url | http://www.karger.com/Article/FullText/452598 |
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