Cargando…
Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway
The major component of the Solenocera crassicornis head protein hydrolysates-fraction 1 (SCHPs-F1) are low molecular weight peptides (MW < 1 kDa). In this study, we investigated the potential renoprotective effects of SCHPs-F1 in a cyclophosphamide (CTX) toxicity mouse model. In brief, 40 male mi...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465301/ https://www.ncbi.nlm.nih.gov/pubmed/32823691 http://dx.doi.org/10.3390/antiox9080745 |
_version_ | 1783577558073212928 |
---|---|
author | Jiang, Shuoqi Zhang, Zhuangwei Huang, FangFang Yang, Zuisu Yu, Fangmiao Tang, Yunping Ding, Guofang |
author_facet | Jiang, Shuoqi Zhang, Zhuangwei Huang, FangFang Yang, Zuisu Yu, Fangmiao Tang, Yunping Ding, Guofang |
author_sort | Jiang, Shuoqi |
collection | PubMed |
description | The major component of the Solenocera crassicornis head protein hydrolysates-fraction 1 (SCHPs-F1) are low molecular weight peptides (MW < 1 kDa). In this study, we investigated the potential renoprotective effects of SCHPs-F1 in a cyclophosphamide (CTX) toxicity mouse model. In brief, 40 male mice were randomly divided into 5 groups and received either saline or 80 mg/kg body weight (BW) CTX by intraperitoneal injection for 5 days, followed by either saline or SCHPs-F1 (100, 200, and 400 mg/kg BW) by intragastric administration for 15 days. SCHPs-F1 treatment significantly reversed the CTX-induced decreases in the levels of blood urea nitrogen (BUN), creatinine (CRE), and cytochrome P450 (CYP450), as well as the renal histological lesions. Furthermore, the results indicated that SCHPs-F1 potentially alleviated CTX-induced nephrotoxicity through mitigating inflammatory responses, oxidative stress, and apoptosis status of the kidneys, as evidenced by decreased levels of malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ and increased levels of total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, overexpression of pro-apoptotic proteins pair B-cell lymphoma-2 (Bcl-2)-associated X (Bax)/Bcl-2, cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 in renal tissues were suppressed by treatment with SCHPs-F1. In addition, the protein levels of the antioxidant factor nuclear factor erythroid-2 related factor 2 (Nrf2) and the expression levels of its downstream target genes heme-oxygenase (HO-1), glutamate-cysteine ligase modifier subunit (GCLM) and NAD(P)H dehydrogenase (quinone) 1 (NQO-1) were stimulated by treatment with SCHPs-F1 in the CTX-induced renal injury model. Taken together, our data suggested that SCHPs-F1 could provide a novel potential strategy in mitigating the nephrotoxicity caused by CTX. |
format | Online Article Text |
id | pubmed-7465301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74653012020-09-04 Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway Jiang, Shuoqi Zhang, Zhuangwei Huang, FangFang Yang, Zuisu Yu, Fangmiao Tang, Yunping Ding, Guofang Antioxidants (Basel) Article The major component of the Solenocera crassicornis head protein hydrolysates-fraction 1 (SCHPs-F1) are low molecular weight peptides (MW < 1 kDa). In this study, we investigated the potential renoprotective effects of SCHPs-F1 in a cyclophosphamide (CTX) toxicity mouse model. In brief, 40 male mice were randomly divided into 5 groups and received either saline or 80 mg/kg body weight (BW) CTX by intraperitoneal injection for 5 days, followed by either saline or SCHPs-F1 (100, 200, and 400 mg/kg BW) by intragastric administration for 15 days. SCHPs-F1 treatment significantly reversed the CTX-induced decreases in the levels of blood urea nitrogen (BUN), creatinine (CRE), and cytochrome P450 (CYP450), as well as the renal histological lesions. Furthermore, the results indicated that SCHPs-F1 potentially alleviated CTX-induced nephrotoxicity through mitigating inflammatory responses, oxidative stress, and apoptosis status of the kidneys, as evidenced by decreased levels of malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ and increased levels of total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, overexpression of pro-apoptotic proteins pair B-cell lymphoma-2 (Bcl-2)-associated X (Bax)/Bcl-2, cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 in renal tissues were suppressed by treatment with SCHPs-F1. In addition, the protein levels of the antioxidant factor nuclear factor erythroid-2 related factor 2 (Nrf2) and the expression levels of its downstream target genes heme-oxygenase (HO-1), glutamate-cysteine ligase modifier subunit (GCLM) and NAD(P)H dehydrogenase (quinone) 1 (NQO-1) were stimulated by treatment with SCHPs-F1 in the CTX-induced renal injury model. Taken together, our data suggested that SCHPs-F1 could provide a novel potential strategy in mitigating the nephrotoxicity caused by CTX. MDPI 2020-08-13 /pmc/articles/PMC7465301/ /pubmed/32823691 http://dx.doi.org/10.3390/antiox9080745 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jiang, Shuoqi Zhang, Zhuangwei Huang, FangFang Yang, Zuisu Yu, Fangmiao Tang, Yunping Ding, Guofang Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway |
title | Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway |
title_full | Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway |
title_fullStr | Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway |
title_full_unstemmed | Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway |
title_short | Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway |
title_sort | protective effect of low molecular weight peptides from solenocera crassicornis head against cyclophosphamide-induced nephrotoxicity in mice via the keap1/nrf2 pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465301/ https://www.ncbi.nlm.nih.gov/pubmed/32823691 http://dx.doi.org/10.3390/antiox9080745 |
work_keys_str_mv | AT jiangshuoqi protectiveeffectoflowmolecularweightpeptidesfromsolenoceracrassicornisheadagainstcyclophosphamideinducednephrotoxicityinmiceviathekeap1nrf2pathway AT zhangzhuangwei protectiveeffectoflowmolecularweightpeptidesfromsolenoceracrassicornisheadagainstcyclophosphamideinducednephrotoxicityinmiceviathekeap1nrf2pathway AT huangfangfang protectiveeffectoflowmolecularweightpeptidesfromsolenoceracrassicornisheadagainstcyclophosphamideinducednephrotoxicityinmiceviathekeap1nrf2pathway AT yangzuisu protectiveeffectoflowmolecularweightpeptidesfromsolenoceracrassicornisheadagainstcyclophosphamideinducednephrotoxicityinmiceviathekeap1nrf2pathway AT yufangmiao protectiveeffectoflowmolecularweightpeptidesfromsolenoceracrassicornisheadagainstcyclophosphamideinducednephrotoxicityinmiceviathekeap1nrf2pathway AT tangyunping protectiveeffectoflowmolecularweightpeptidesfromsolenoceracrassicornisheadagainstcyclophosphamideinducednephrotoxicityinmiceviathekeap1nrf2pathway AT dingguofang protectiveeffectoflowmolecularweightpeptidesfromsolenoceracrassicornisheadagainstcyclophosphamideinducednephrotoxicityinmiceviathekeap1nrf2pathway |