Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice

Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named “Bangyakhappyeon” in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficienc...

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Autores principales: Byung Hyuk Han, Hyeon Kyoung Lee, Se Hoon Jang, Ai Lin Tai, Youn Jae Jang, Jung Joo Yoon, Hye Yoom Kim, Ho Sub Lee, Yun Jung Lee, Dae Gill Kang
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/e1fd5f0864964e5dbdd9de17daa137e3
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spelling oai:doaj.org-article:e1fd5f0864964e5dbdd9de17daa137e32021-11-25T18:34:43ZEffect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice10.3390/nu131138592072-6643https://doaj.org/article/e1fd5f0864964e5dbdd9de17daa137e32021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/3859https://doaj.org/toc/2072-6643Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named “Bangyakhappyeon” in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficiency of kidney yang and insufficiency of kidney gi. Here we investigate the effects of GSH in mice model of ischemic acute kidney injury. The mice groups are as follows; sham group: C57BL6 male mice, I/R group: C57BL6 male mice with I/R surgery, GSH low group: I/R + 100 mg/kg/day GSH, and GSH high group: I/R + 300 mg/kg/day GSH. Ischemia was induced by clamping both renal arteries and reperfusion. Mice were orally given GSH (100 and 300 mg/kg/day) during 3 days after surgery. Treatment with GSH significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen levels. Treatment with GSH reduced neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), specific renal injury markers. GSH also reduced the periodic acid–Schiff and picro sirius red staining intensity in kidney of I/R group. Western blot and real-time RT-qPCR analysis demonstrated that GSH decreased protein and mRNA expression levels of the inflammatory cytokines in I/R-induced ARF mice. Moreover, GSH inhibited protein and mRNA expression of inflammasome-related protein including NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryoprin), ASC (Apoptosis-associated speck-like protein containing a CARD), and caspase-1. These findings provided evidence that GSH ameliorates renal injury including metabolic dysfunction and inflammation via the inhibition of NLRP3-dependent inflammasome in I/R-induced ARF mice.Byung Hyuk HanHyeon Kyoung LeeSe Hoon JangAi Lin TaiYoun Jae JangJung Joo YoonHye Yoom KimHo Sub LeeYun Jung LeeDae Gill KangMDPI AGarticlegeumgwe-sinkihwanischemia/reperfusioncreatinineNGALKIM-1fibrosisNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 3859, p 3859 (2021)
institution DOAJ
collection DOAJ
language EN
topic geumgwe-sinkihwan
ischemia/reperfusion
creatinine
NGAL
KIM-1
fibrosis
Nutrition. Foods and food supply
TX341-641
spellingShingle geumgwe-sinkihwan
ischemia/reperfusion
creatinine
NGAL
KIM-1
fibrosis
Nutrition. Foods and food supply
TX341-641
Byung Hyuk Han
Hyeon Kyoung Lee
Se Hoon Jang
Ai Lin Tai
Youn Jae Jang
Jung Joo Yoon
Hye Yoom Kim
Ho Sub Lee
Yun Jung Lee
Dae Gill Kang
Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice
description Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named “Bangyakhappyeon” in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficiency of kidney yang and insufficiency of kidney gi. Here we investigate the effects of GSH in mice model of ischemic acute kidney injury. The mice groups are as follows; sham group: C57BL6 male mice, I/R group: C57BL6 male mice with I/R surgery, GSH low group: I/R + 100 mg/kg/day GSH, and GSH high group: I/R + 300 mg/kg/day GSH. Ischemia was induced by clamping both renal arteries and reperfusion. Mice were orally given GSH (100 and 300 mg/kg/day) during 3 days after surgery. Treatment with GSH significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen levels. Treatment with GSH reduced neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), specific renal injury markers. GSH also reduced the periodic acid–Schiff and picro sirius red staining intensity in kidney of I/R group. Western blot and real-time RT-qPCR analysis demonstrated that GSH decreased protein and mRNA expression levels of the inflammatory cytokines in I/R-induced ARF mice. Moreover, GSH inhibited protein and mRNA expression of inflammasome-related protein including NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryoprin), ASC (Apoptosis-associated speck-like protein containing a CARD), and caspase-1. These findings provided evidence that GSH ameliorates renal injury including metabolic dysfunction and inflammation via the inhibition of NLRP3-dependent inflammasome in I/R-induced ARF mice.
format article
author Byung Hyuk Han
Hyeon Kyoung Lee
Se Hoon Jang
Ai Lin Tai
Youn Jae Jang
Jung Joo Yoon
Hye Yoom Kim
Ho Sub Lee
Yun Jung Lee
Dae Gill Kang
author_facet Byung Hyuk Han
Hyeon Kyoung Lee
Se Hoon Jang
Ai Lin Tai
Youn Jae Jang
Jung Joo Yoon
Hye Yoom Kim
Ho Sub Lee
Yun Jung Lee
Dae Gill Kang
author_sort Byung Hyuk Han
title Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice
title_short Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice
title_full Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice
title_fullStr Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice
title_full_unstemmed Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice
title_sort effect of geumgwe-sinkihwan on renal dysfunction in ischemia/reperfusion-induced acute renal failure mice
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/e1fd5f0864964e5dbdd9de17daa137e3
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