SS-31 for diabetic nephropathy

Excerpt:


J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 956-971, Sep-Oct 2024. DOI: https://doi.org/10.56499/jppres23.1904_12.5.956 Review SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies [El SS-31 protege la progresión de la nefropatía diabética: Una revisión sistemática de estudios in vivo e in vitro] Jonathan Christianto Sutadji1#, Dian Anggraini Permatasari … Continue reading SS-31 for diabetic nephropathy

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 956-971, Sep-Oct 2024.

DOI: https://doi.org/10.56499/jppres23.1904_12.5.956

Review

SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies

[El SS-31 protege la progresión de la nefropatía diabética: Una revisión sistemática de estudios in vivo e in vitro]

Jonathan Christianto Sutadji1#, Dian Anggraini Permatasari Musalim1#, David Setyo Budi1#, Jennifer Susanto1, Fanny Gunawan1, Chaq El Chaq Zamzam Multazam2, Citrawati Dyah Kencono Wungu3,4*

1Faculty of Medicine, Universitas Airlangga, Indonesia.

2National Heart and Lung Institute, Imperial College London, London, United Kingdom.

3Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Indonesia.

4Institute of Tropical Disease, Universitas Airlangga, Indonesia.

#JCS, DAPM, and DSB are joint first authors.

*E-mail: citrawati.dyah@fk.unair.ac.id

Abstract

Context: Diabetic nephropathy is the leading cause of end-stage renal disease and also death in the world. Administration of Szeto-Schiller-31 (SS-31) as a potential therapeutic candidate that can decrease the renal function damage progressivity in diabetes needs to be comprehensively analyzed.

Aims: To assess the protective effects of SS31 against the progressivity of diabetic nephropathy.

Methods: This systematic review follows PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines 2020. Searches of databases (Pubmed, Science Direct, Scopus, ProQuest, and Springer) were done on 17 September 2023 in order to find articles related to the animal diabetic model and SS-31 treatment. Manual searches from medRxiv were also conducted to obtain additional evidence. Renal function, histopathology analysis, reactive oxygen species in vivo, and in vitro analysis were described.

Results: There were six in vivo studies, each of which discussed the renal function, histopathology, and reactive oxygen species (ROS), and four in vitro studies that discussed ROS. The available data suggested that SS-31 improves kidney function by lowering urinary albumin excretion, proteinuria, serum creatinine, creatinine clearance, and BUN, supported by histopathological improvements. In addition, SS-31 also has the effect of lowering 8-hydroxy-2-deoxyguanosine (8-OHdG) level, malondialdehyde (MDA) level, and nicotinamide adenine dinucleotide phosphate (NADPH) expression.

Conclusions: SS31 had a renoprotective effect that could prevent the worsening of renal function in diabetic mice. In addition, the results of histopathology and ROS analysis also support the positive results of SS-31 treatment. Further studies are required to confirm its findings.

Keywords: diabetic nephropathy; elamipretide; mitochondria targeted peptide; SS-31.

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Resumen

Contexto: La nefropatía diabética es la principal causa de enfermedad renal terminal y también de muerte en el mundo. Es necesario analizar exhaustivamente la administración de Szeto-Schiller-31 (SS-31) como posible candidato terapéutico capaz de disminuir la progresividad del daño de la función renal en la diabetes.

Objetivos: Evaluar los efectos protectores del SS31 contra la progresividad de la nefropatía diabética.

Métodos: Esta revisión sistemática sigue las directrices PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) 2020. Se realizaron búsquedas en bases de datos (Pubmed, Science Direct, Scopus, ProQuest y Springer) el 17 de septiembre de 2023 para encontrar artículos relacionados con el modelo diabético animal y el tratamiento con SS-31. También se realizaron búsquedas manuales en medRxiv para obtener pruebas adicionales. Se describieron la función renal, el análisis histopatológico, las especies reactivas de oxígeno in vivo y el análisis in vitro.

Resultados: Hubo seis estudios in vivo, cada uno de los cuales analizaba la función renal, la histopatología y las especies reactivas del oxígeno (ROS), y cuatro estudios in vitro que analizaban las ROS. Los datos disponibles sugirieron que el SS-31 mejora la función renal al reducir la excreción urinaria de albúmina, la proteinuria, la creatinina sérica, el aclaramiento de creatinina y el BUN, apoyado por mejoras histopatológicas. Además, el SS-31 también tiene el efecto de reducir el nivel de 8-hidroxi-2-deoxiguanosina (8-OHdG), el nivel de malondialdehído (MDA) y la expresión de nicotinamida adenina dinucleótido fosfato (NADPH).

Conclusiones: El SS31 tuvo un efecto renoprotector que pudo prevenir el empeoramiento de la función renal en ratones diabéticos. Además, los resultados de la histopatología y el análisis de ROS también apoyan los resultados positivos del tratamiento con SS-31. Se requieren más estudios para confirmar sus resultados.

Palabras Clave: elamipretida; nefropatía diabética; péptido dirigido a las mitocondrias; SS-31.

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Citation Format: Sutadji JC, Musalim DAP, Budi DS, Susanto J, Gunawan F, Multazam CEZ, Wungu CDK (2024) SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies. J Pharm Pharmacogn Res 12(5): 956–971. https://doi.org/10.56499/jppres23.1904_12.5.956
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