A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice
Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY41...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/8145785 |
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| author | Mi Liu Zhanjun Jia Ying Sun Aihua Zhang Tianxin Yang |
| author_facet | Mi Liu Zhanjun Jia Ying Sun Aihua Zhang Tianxin Yang |
| author_sort | Mi Liu |
| collection | DOAJ |
| description | Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage. Consistently, these mice also showed increased proinflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and/or kidney tissues. Meanwhile, circulating thiobarbituric aid-reactive substances (TBARS) and renal apoptotic indices including caspase-3, Bak, and Bax were all elevated. However, application of GYY4137 further aggravated renal dysfunction and kidney structural injury in line with promoted inflammation, oxidative stress, and apoptotic response following cisplatin treatment. Taken together, our results suggested that GYY4137 exacerbated cisplatin-induced nephrotoxicity in mice possibly through promoting inflammation, oxidative stress, and apoptotic response. |
| format | Article |
| id | doaj-art-551c8d6929ed41c3bc0c8b054df73b24 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-551c8d6929ed41c3bc0c8b054df73b242025-02-03T07:26:19ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/81457858145785A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in MiceMi Liu0Zhanjun Jia1Ying Sun2Aihua Zhang3Tianxin Yang4Institute of Hypertension, Sun Yat-Sen University School of Medicine, No. 74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou 510080, ChinaDepartment of Medicine and Veterans Affairs Medical Center, University of Utah, Salt Lake City, UT 84132, USADepartment of Medicine and Veterans Affairs Medical Center, University of Utah, Salt Lake City, UT 84132, USANanjing Key Laboratory of Pediatrics, Nanjing 210008, ChinaInstitute of Hypertension, Sun Yat-Sen University School of Medicine, No. 74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou 510080, ChinaAccumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage. Consistently, these mice also showed increased proinflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and/or kidney tissues. Meanwhile, circulating thiobarbituric aid-reactive substances (TBARS) and renal apoptotic indices including caspase-3, Bak, and Bax were all elevated. However, application of GYY4137 further aggravated renal dysfunction and kidney structural injury in line with promoted inflammation, oxidative stress, and apoptotic response following cisplatin treatment. Taken together, our results suggested that GYY4137 exacerbated cisplatin-induced nephrotoxicity in mice possibly through promoting inflammation, oxidative stress, and apoptotic response.http://dx.doi.org/10.1155/2016/8145785 |
| spellingShingle | Mi Liu Zhanjun Jia Ying Sun Aihua Zhang Tianxin Yang A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice Mediators of Inflammation |
| title | A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice |
| title_full | A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice |
| title_fullStr | A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice |
| title_full_unstemmed | A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice |
| title_short | A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice |
| title_sort | h2s donor gyy4137 exacerbates cisplatin induced nephrotoxicity in mice |
| url | http://dx.doi.org/10.1155/2016/8145785 |
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