IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic Rats
Diabetic bladder dysfunction (DBD) afflicts nearly half of diabetic patients, but effective treatment is lacking. In this study, IR-61, a novel heptamethine cyanine dye with potential antioxidant effects, was investigated to determine whether it can alleviate DBD. Rats were intraperitoneally injecte...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-04-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.608637/full |
| _version_ | 1819139065194217472 |
|---|---|
| author | Jianwu Wang Linyong Dai Xiaofeng Yue Chongxing Shen Tong Li Lei Long Yi Zhi Yawei Wang Gufang Shen Chunmeng Shi Yunsheng Liu Qiang Fang Weibing Li |
| author_facet | Jianwu Wang Linyong Dai Xiaofeng Yue Chongxing Shen Tong Li Lei Long Yi Zhi Yawei Wang Gufang Shen Chunmeng Shi Yunsheng Liu Qiang Fang Weibing Li |
| author_sort | Jianwu Wang |
| collection | DOAJ |
| description | Diabetic bladder dysfunction (DBD) afflicts nearly half of diabetic patients, but effective treatment is lacking. In this study, IR-61, a novel heptamethine cyanine dye with potential antioxidant effects, was investigated to determine whether it can alleviate DBD. Rats were intraperitoneally injected with IR-61 or vehicle after diabetes was induced with streptozotocin. Before evaluating the effects of IR-61 in improving DBD by filling cystometry, we detected its distribution in tissues and subcellular organelles by confocal fluorescence imaging. Near infrared (NIR) imaging showed that IR-61 could accumulate at high levels in the bladders of diabetic rats, and confocal images demonstrated that it was mainly taken up by bladder smooth muscle cells (BSMCs) and localized in mitochondria. Then, filling cystometry illustrated that IR-61 significantly improved the bladder function of diabetic rats. The histomorphometry results showed that IR-61 effectively mitigated the pathological changes in bladder smooth muscle (BSM) in diabetic rats. Furthermore, IR-61 remarkably reduced the number of apoptotic BSMCs and the unfavorable expression of proteins related to the mitochondrial apoptotic pathway (Bcl-2, BAX, Cytochrome C, and cleaved Caspase-9) in diabetic rats. Moreover, the frozen section staining and transmission electron microscopy results proved that IR-61 significantly reduced the reactive oxygen species (ROS) levels and prevented the mitochondrial mass and morphology damage in the BSM of diabetic rats. In addition, IR-61 upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its associated antioxidant proteins in the BSM of diabetic rats. Together, these results indicate that IR-61 can improve the voiding function of rats with DBD by protecting the mitochondria of BSMCs from oxidative stress, which is possibly mediated through the activation of the Nrf2 pathway. |
| first_indexed | 2024-12-22T11:16:44Z |
| format | Article |
| id | doaj.art-69cb26be78304e2fa0a832951d572331 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T11:16:44Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-69cb26be78304e2fa0a832951d5723312022-12-21T18:27:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.608637608637IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic RatsJianwu Wang0Linyong Dai1Xiaofeng Yue2Chongxing Shen3Tong Li4Lei Long5Yi Zhi6Yawei Wang7Gufang Shen8Chunmeng Shi9Yunsheng Liu10Qiang Fang11Weibing Li12Department of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaDepartment of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaDepartment of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaDepartment of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaDepartment of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University, Chongqing, ChinaDepartment of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University, Chongqing, ChinaDepartment of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaDepartment of Urology, The Third Affiliated Hospital (Gener Hospital) of Chongqing Medical University, Chongqing, ChinaDiabetic bladder dysfunction (DBD) afflicts nearly half of diabetic patients, but effective treatment is lacking. In this study, IR-61, a novel heptamethine cyanine dye with potential antioxidant effects, was investigated to determine whether it can alleviate DBD. Rats were intraperitoneally injected with IR-61 or vehicle after diabetes was induced with streptozotocin. Before evaluating the effects of IR-61 in improving DBD by filling cystometry, we detected its distribution in tissues and subcellular organelles by confocal fluorescence imaging. Near infrared (NIR) imaging showed that IR-61 could accumulate at high levels in the bladders of diabetic rats, and confocal images demonstrated that it was mainly taken up by bladder smooth muscle cells (BSMCs) and localized in mitochondria. Then, filling cystometry illustrated that IR-61 significantly improved the bladder function of diabetic rats. The histomorphometry results showed that IR-61 effectively mitigated the pathological changes in bladder smooth muscle (BSM) in diabetic rats. Furthermore, IR-61 remarkably reduced the number of apoptotic BSMCs and the unfavorable expression of proteins related to the mitochondrial apoptotic pathway (Bcl-2, BAX, Cytochrome C, and cleaved Caspase-9) in diabetic rats. Moreover, the frozen section staining and transmission electron microscopy results proved that IR-61 significantly reduced the reactive oxygen species (ROS) levels and prevented the mitochondrial mass and morphology damage in the BSM of diabetic rats. In addition, IR-61 upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its associated antioxidant proteins in the BSM of diabetic rats. Together, these results indicate that IR-61 can improve the voiding function of rats with DBD by protecting the mitochondria of BSMCs from oxidative stress, which is possibly mediated through the activation of the Nrf2 pathway.https://www.frontiersin.org/articles/10.3389/fphar.2021.608637/fullbladder smooth muscle cellsdiabetic bladder dysfunctionIR-61mitochondrianuclear factor erythroid 2-related factor 2 |
| spellingShingle | Jianwu Wang Linyong Dai Xiaofeng Yue Chongxing Shen Tong Li Lei Long Yi Zhi Yawei Wang Gufang Shen Chunmeng Shi Yunsheng Liu Qiang Fang Weibing Li IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic Rats Frontiers in Pharmacology bladder smooth muscle cells diabetic bladder dysfunction IR-61 mitochondria nuclear factor erythroid 2-related factor 2 |
| title | IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic Rats |
| title_full | IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic Rats |
| title_fullStr | IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic Rats |
| title_full_unstemmed | IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic Rats |
| title_short | IR-61 Improves Voiding Function via Mitochondrial Protection in Diabetic Rats |
| title_sort | ir 61 improves voiding function via mitochondrial protection in diabetic rats |
| topic | bladder smooth muscle cells diabetic bladder dysfunction IR-61 mitochondria nuclear factor erythroid 2-related factor 2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.608637/full |
| work_keys_str_mv | AT jianwuwang ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT linyongdai ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT xiaofengyue ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT chongxingshen ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT tongli ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT leilong ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT yizhi ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT yaweiwang ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT gufangshen ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT chunmengshi ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT yunshengliu ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT qiangfang ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats AT weibingli ir61improvesvoidingfunctionviamitochondrialprotectionindiabeticrats |