Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats

Nur Samsu,1 Setyawati Soeharto,2 Muhaimin Rifai,3 Achmad Rudijanto41Department of Internal Medicine, Division of Nephrology and Hypertension, Faculty of Medicine; 2Department of Pharmacology, Faculty of Medicine; 3Department of Biology, Faculty of Mathematics and Sciences; 4Department of Internal Me...

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Autores principales:	Samsu N, Soeharto S, Rifai M, Rudijanto A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	rosmarinic acid telmisartan podocin nephrin diabetic nephropathy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/dfb10b83fb5e44e79a63eaa11fe96430
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spelling	oai:doaj.org-article:dfb10b83fb5e44e79a63eaa11fe964302021-12-02T09:29:15ZRosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats1177-5491https://doaj.org/article/dfb10b83fb5e44e79a63eaa11fe964302019-08-01T00:00:00Zhttps://www.dovepress.com/rosmarinic-acid-monotherapy-is-better-than-the-combination-of-rosmarin-peer-reviewed-article-BTThttps://doaj.org/toc/1177-5491Nur Samsu,1 Setyawati Soeharto,2 Muhaimin Rifai,3 Achmad Rudijanto41Department of Internal Medicine, Division of Nephrology and Hypertension, Faculty of Medicine; 2Department of Pharmacology, Faculty of Medicine; 3Department of Biology, Faculty of Mathematics and Sciences; 4Department of Internal Medicine, Division of Endocrinology and Metabolic, Faculty of Medicine, Universitas Brawijaya, Malang, IndonesiaCorrespondence: Nur SamsuDepartment of Internal Medicine, Division of Nephrology and Hypertension, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65122, IndonesiaTel +62 812 331 6315Email samsu_nrs@yahoo.comBackground: Podocyte injury and its subsequent detachment play a critical role in the development and progression of diabetic nephropathy (DN). The objective of this study was to investigate the effect of rosmarinic acid (RA) in preventing podocyte detachment and inhibiting the progression of DN in streptozotocin (STZ)-induced diabetic in rats.Methods: We used 20 adult male Wistar rats as experimental animals, which were randomly divided into 5 groups (n=4 per group): nondiabetic rat group (negative control) and 4 groups of STZ-induced diabetic rats, namely, 1 group untreated diabetic rats (positive control) and 3 groups treated diabetic rats with RA 75 mg/kg, telmisartan (TMS) 1 mg/kg and combination of RA 75 mg/kg with TMS 1 mg/kg), respectively. After 8 weeks of therapy, urinary levels of podocin, nephrin and albumin and also serum cystatin C levels were examined by ELISA. The expression of p65 nuclear factor-kB by immunohistochemistry whereas expression of podocin and nephrin glomerulus were examined by immunofluorescence.Results: In the treated diabetic groups, we found that urinary level of podocin and nephrin, albumin urine excretion and serum cystatin C levels were significantly lower than the positive control group. Compared to negative controls, the group of treated diabetic rats did not differ significantly in preventing increased excretion of urinary nephrin and podocin. Meanwhile, treatment with RA monotherapy was significantly better than TMS or a combination of RA with TMS in reducing albumin excretion and preventing decreased kidney function.Conclusion: In STZ-induced diabetic rats, RA can prevent podocyte detachment. Treatment with RA and TMS either monotherapy or in combination can inhibit the development and progression of DN. However, the combination of both did not show a synergistic effect, even have higher urinary albumin excretion and worse kidney function compared to the RA monotherapy.Keywords: rosmarinic acid, telmisartan, podocin, nephrin, diabetic nephropathySamsu NSoeharto SRifai MRudijanto ADove Medical Pressarticlerosmarinic acidtelmisartanpodocinnephrindiabetic nephropathyMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol Volume 13, Pp 179-190 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	rosmarinic acid telmisartan podocin nephrin diabetic nephropathy Medicine (General) R5-920
spellingShingle	rosmarinic acid telmisartan podocin nephrin diabetic nephropathy Medicine (General) R5-920 Samsu N Soeharto S Rifai M Rudijanto A Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats
description	Nur Samsu,1 Setyawati Soeharto,2 Muhaimin Rifai,3 Achmad Rudijanto41Department of Internal Medicine, Division of Nephrology and Hypertension, Faculty of Medicine; 2Department of Pharmacology, Faculty of Medicine; 3Department of Biology, Faculty of Mathematics and Sciences; 4Department of Internal Medicine, Division of Endocrinology and Metabolic, Faculty of Medicine, Universitas Brawijaya, Malang, IndonesiaCorrespondence: Nur SamsuDepartment of Internal Medicine, Division of Nephrology and Hypertension, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65122, IndonesiaTel +62 812 331 6315Email samsu_nrs@yahoo.comBackground: Podocyte injury and its subsequent detachment play a critical role in the development and progression of diabetic nephropathy (DN). The objective of this study was to investigate the effect of rosmarinic acid (RA) in preventing podocyte detachment and inhibiting the progression of DN in streptozotocin (STZ)-induced diabetic in rats.Methods: We used 20 adult male Wistar rats as experimental animals, which were randomly divided into 5 groups (n=4 per group): nondiabetic rat group (negative control) and 4 groups of STZ-induced diabetic rats, namely, 1 group untreated diabetic rats (positive control) and 3 groups treated diabetic rats with RA 75 mg/kg, telmisartan (TMS) 1 mg/kg and combination of RA 75 mg/kg with TMS 1 mg/kg), respectively. After 8 weeks of therapy, urinary levels of podocin, nephrin and albumin and also serum cystatin C levels were examined by ELISA. The expression of p65 nuclear factor-kB by immunohistochemistry whereas expression of podocin and nephrin glomerulus were examined by immunofluorescence.Results: In the treated diabetic groups, we found that urinary level of podocin and nephrin, albumin urine excretion and serum cystatin C levels were significantly lower than the positive control group. Compared to negative controls, the group of treated diabetic rats did not differ significantly in preventing increased excretion of urinary nephrin and podocin. Meanwhile, treatment with RA monotherapy was significantly better than TMS or a combination of RA with TMS in reducing albumin excretion and preventing decreased kidney function.Conclusion: In STZ-induced diabetic rats, RA can prevent podocyte detachment. Treatment with RA and TMS either monotherapy or in combination can inhibit the development and progression of DN. However, the combination of both did not show a synergistic effect, even have higher urinary albumin excretion and worse kidney function compared to the RA monotherapy.Keywords: rosmarinic acid, telmisartan, podocin, nephrin, diabetic nephropathy
format	article
author	Samsu N Soeharto S Rifai M Rudijanto A
author_facet	Samsu N Soeharto S Rifai M Rudijanto A
author_sort	Samsu N
title	Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats
title_short	Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats
title_full	Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats
title_fullStr	Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats
title_full_unstemmed	Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats
title_sort	rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/dfb10b83fb5e44e79a63eaa11fe96430
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Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats

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