Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model
Sodium thiosulfate (STS), a precursor of hydrogen sulfide (H<sub>2</sub>S), has demonstrated antihypertensive properties. Previous studies have suggested that H<sub>2</sub>S-based interventions can prevent hypertension in pediatric chronic kidney disease (CKD). However, the c...
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MDPI AG
2024-12-01
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| author | You-Lin Tain Chien-Ning Hsu Chih-Yao Hou Chih-Kuang Chen |
| author_facet | You-Lin Tain Chien-Ning Hsu Chih-Yao Hou Chih-Kuang Chen |
| author_sort | You-Lin Tain |
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| description | Sodium thiosulfate (STS), a precursor of hydrogen sulfide (H<sub>2</sub>S), has demonstrated antihypertensive properties. Previous studies have suggested that H<sub>2</sub>S-based interventions can prevent hypertension in pediatric chronic kidney disease (CKD). However, the clinical application of STS is limited by its rapid release and intravenous administration. To address this, we developed a poly-lactic acid (PLA)-based nanoparticle system for sustained STS delivery and investigated whether weekly treatment with STS-loaded nanoparticles (NPs) could protect against hypertension in a juvenile CKD rat model. Male Sprague Dawley rats, aged three weeks, were fed a diet containing 0.5% adenine for three weeks to induce a model of pediatric CKD. STS-loaded NPs (25 mg/kg) were administered intravenously during weeks 6, 7, and 8, and at week 9, all rats were sacrificed. Treatment with STS-loaded NPs reduced systolic and diastolic blood pressure by 10 mm Hg and 8 mm Hg, respectively, in juvenile CKD rats. The protective effect of STS-loaded NPs was linked to increased renal expression of H<sub>2</sub>S-producing enzymes, including cystathionine γ-lyase (<i>CSE</i>) and D-amino acid oxidase (<i>DAO</i>). Additionally, STS-loaded NP therapy restored nitric oxide (NO) signaling, increasing L-arginine levels, which were disrupted in CKD. Furthermore, the beneficial effects of STS-loaded NPs were associated with inhibition of the renin–angiotensin system (RAS) and the enhancement of the NO signaling pathway. Our findings suggest that STS-loaded NP treatment provides sustained STS delivery and effectively reduces hypertension in a juvenile CKD rat model, bringing us closer to the clinical translation of STS-based therapy for pediatric CKD-induced hypertension. |
| format | Article |
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| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-d755fb25d96a4bb68f1d5e885028b0a82025-08-20T02:53:40ZengMDPI AGAntioxidants2076-39212024-12-011312157410.3390/antiox13121574Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat ModelYou-Lin Tain0Chien-Ning Hsu1Chih-Yao Hou2Chih-Kuang Chen3Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, TaiwanPolymeric Biomaterials Laboratory, Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 804, TaiwanSodium thiosulfate (STS), a precursor of hydrogen sulfide (H<sub>2</sub>S), has demonstrated antihypertensive properties. Previous studies have suggested that H<sub>2</sub>S-based interventions can prevent hypertension in pediatric chronic kidney disease (CKD). However, the clinical application of STS is limited by its rapid release and intravenous administration. To address this, we developed a poly-lactic acid (PLA)-based nanoparticle system for sustained STS delivery and investigated whether weekly treatment with STS-loaded nanoparticles (NPs) could protect against hypertension in a juvenile CKD rat model. Male Sprague Dawley rats, aged three weeks, were fed a diet containing 0.5% adenine for three weeks to induce a model of pediatric CKD. STS-loaded NPs (25 mg/kg) were administered intravenously during weeks 6, 7, and 8, and at week 9, all rats were sacrificed. Treatment with STS-loaded NPs reduced systolic and diastolic blood pressure by 10 mm Hg and 8 mm Hg, respectively, in juvenile CKD rats. The protective effect of STS-loaded NPs was linked to increased renal expression of H<sub>2</sub>S-producing enzymes, including cystathionine γ-lyase (<i>CSE</i>) and D-amino acid oxidase (<i>DAO</i>). Additionally, STS-loaded NP therapy restored nitric oxide (NO) signaling, increasing L-arginine levels, which were disrupted in CKD. Furthermore, the beneficial effects of STS-loaded NPs were associated with inhibition of the renin–angiotensin system (RAS) and the enhancement of the NO signaling pathway. Our findings suggest that STS-loaded NP treatment provides sustained STS delivery and effectively reduces hypertension in a juvenile CKD rat model, bringing us closer to the clinical translation of STS-based therapy for pediatric CKD-induced hypertension.https://www.mdpi.com/2076-3921/13/12/1574chronic kidney diseasehydrogen sulfidehypertensionnitric oxiderenin–angiotensin systemsodium thiosulfate |
| spellingShingle | You-Lin Tain Chien-Ning Hsu Chih-Yao Hou Chih-Kuang Chen Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model Antioxidants chronic kidney disease hydrogen sulfide hypertension nitric oxide renin–angiotensin system sodium thiosulfate |
| title | Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model |
| title_full | Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model |
| title_fullStr | Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model |
| title_full_unstemmed | Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model |
| title_short | Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model |
| title_sort | antihypertensive effects of a sodium thiosulfate loaded nanoparticle in a juvenile chronic kidney disease rat model |
| topic | chronic kidney disease hydrogen sulfide hypertension nitric oxide renin–angiotensin system sodium thiosulfate |
| url | https://www.mdpi.com/2076-3921/13/12/1574 |
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