Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternativ...

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Main Authors: Hyesook Lee, Seon Yeong Ji, Hyun Hwangbo, Min Yeong Kim, Da Hye Kim, Beom Su Park, Joung-Hyun Park, Bae-Jin Lee, Gi-Young Kim, You-Jin Jeon, Yung Hyun Choi
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/1/502
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author Hyesook Lee
Seon Yeong Ji
Hyun Hwangbo
Min Yeong Kim
Da Hye Kim
Beom Su Park
Joung-Hyun Park
Bae-Jin Lee
Gi-Young Kim
You-Jin Jeon
Yung Hyun Choi
author_facet Hyesook Lee
Seon Yeong Ji
Hyun Hwangbo
Min Yeong Kim
Da Hye Kim
Beom Su Park
Joung-Hyun Park
Bae-Jin Lee
Gi-Young Kim
You-Jin Jeon
Yung Hyun Choi
author_sort Hyesook Lee
collection DOAJ
description Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with <i>L</i>. <i>brevis</i> BJ20 and <i>L</i>. <i>plantarum</i> BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.
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spelling doaj.art-5be3d9c38c10475da25c41fbc8001e412023-11-23T11:40:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123150210.3390/ijms23010502Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced NephrotoxicityHyesook Lee0Seon Yeong Ji1Hyun Hwangbo2Min Yeong Kim3Da Hye Kim4Beom Su Park5Joung-Hyun Park6Bae-Jin Lee7Gi-Young Kim8You-Jin Jeon9Yung Hyun Choi10Department of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, KoreaDepartment of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, KoreaKorea Nanobiotechnology Center, Pusan National University, Busan 46241, KoreaDepartment of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, KoreaDepartment of Molecular Biology, Pusan National University, Busan 46241, KoreaDepartment of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, KoreaOcean Fisheries & Biology Center, Marine Bioprocess Co., Ltd., Busan 46048, KoreaOcean Fisheries & Biology Center, Marine Bioprocess Co., Ltd., Busan 46048, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, KoreaGamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with <i>L</i>. <i>brevis</i> BJ20 and <i>L</i>. <i>plantarum</i> BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.https://www.mdpi.com/1422-0067/23/1/502cisplatingamma-aminobutyric acidkidneynephrotoxicitysalt
spellingShingle Hyesook Lee
Seon Yeong Ji
Hyun Hwangbo
Min Yeong Kim
Da Hye Kim
Beom Su Park
Joung-Hyun Park
Bae-Jin Lee
Gi-Young Kim
You-Jin Jeon
Yung Hyun Choi
Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
International Journal of Molecular Sciences
cisplatin
gamma-aminobutyric acid
kidney
nephrotoxicity
salt
title Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
title_full Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
title_fullStr Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
title_full_unstemmed Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
title_short Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
title_sort protective effect of gamma aminobutyric acid against aggravation of renal injury caused by high salt intake in cisplatin induced nephrotoxicity
topic cisplatin
gamma-aminobutyric acid
kidney
nephrotoxicity
salt
url https://www.mdpi.com/1422-0067/23/1/502
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