S-Propargyl-cysteine prevents concanavalin A-induced immunological liver injury in mice

S-Propargyl-cysteine (SPRC), an endogenous H 2 S modulator, exerts anti-inflammatory effects on cardiovascular and neurodegenerative disease, but it remains unknown whether SPRC can prevent autoimmune hepatitis. To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury...

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Veröffentlicht in:Pharmaceutical biology 2022-12, Vol.60 (1), p.1169-1176
Hauptverfasser: Ma, Beilei, Mao, Yicheng, Chang, Lingling, Dai, Tao, Xin, Xiaoming, Ma, Fenfen, Wang, Zhijun, Shen, Zhuqing, Mei, Qibing, Zhu, Yizhun
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container_title Pharmaceutical biology
container_volume 60
creator Ma, Beilei
Mao, Yicheng
Chang, Lingling
Dai, Tao
Xin, Xiaoming
Ma, Fenfen
Wang, Zhijun
Shen, Zhuqing
Mei, Qibing
Zhu, Yizhun
description S-Propargyl-cysteine (SPRC), an endogenous H 2 S modulator, exerts anti-inflammatory effects on cardiovascular and neurodegenerative disease, but it remains unknown whether SPRC can prevent autoimmune hepatitis. To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury and uncover the underlying mechanisms. Mice were randomly divided into five groups: control, Con A, SPRC (5 and 10 mg/kg injected intravenously once a day for 7 days), and propargylglycine (PAG; 50 mg/kg injected intraperitoneally 0.5 h before SPRC for 7 days). All mice except the controls were intravenously injected with Con A (20 mg/kg) on day 7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using kits. Inflammatory cytokines (TNF-α and IFN-γ) in the blood and in the liver were detected by ELISA Kit and real-time PCR, respectively. The expression of mitogen-activated protein kinase (MAPK) pathway proteins (p-JNK and p-Akt) and apoptosis proteins (Bax and Bcl-2) was detected using western blotting. SPRC reduced the levels of AST (p 
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To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury and uncover the underlying mechanisms. Mice were randomly divided into five groups: control, Con A, SPRC (5 and 10 mg/kg injected intravenously once a day for 7 days), and propargylglycine (PAG; 50 mg/kg injected intraperitoneally 0.5 h before SPRC for 7 days). All mice except the controls were intravenously injected with Con A (20 mg/kg) on day 7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using kits. Inflammatory cytokines (TNF-α and IFN-γ) in the blood and in the liver were detected by ELISA Kit and real-time PCR, respectively. The expression of mitogen-activated protein kinase (MAPK) pathway proteins (p-JNK and p-Akt) and apoptosis proteins (Bax and Bcl-2) was detected using western blotting. SPRC reduced the levels of AST (p &lt; 0.05) and ALT (p &lt; 0.01) and decreased the release of the inflammatory cytokines. Mechanistically, SPRC increased H 2 S level (p &lt; 0.05) and promoted cystathionine γ-lyase (CSE) expression (p &lt; 0.05). SPRC inhibited the MAPK pathway activation and the apoptosis pathway. All the effects of SPRC were blocked by the CSE inhibitor PAG. SPRC prevents Con A-induced liver injury in mice by promoting CSE expression and producing endogenous H 2 S. The mechanisms include reducing the release of inflammatory cytokines, attenuating MAPK pathway activation, and alleviating apoptosis.</description><identifier>ISSN: 1388-0209</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2022.2080234</identifier><identifier>PMID: 35701112</identifier><language>eng</language><publisher>England: Taylor &amp; Francis</publisher><subject>AKT protein ; Alanine transaminase ; Apoptosis ; Aspartate aminotransferase ; autoimmune hepatitis ; BAX protein ; Bcl-2 protein ; Concanavalin A ; Cystathionine g-lyase ; cystathionine γ-lyase ; Cysteine ; Cytokines ; Enzyme-linked immunosorbent assay ; Hepatitis ; Hydrogen sulfide ; Hydrogen sulphide ; Inflammation ; Kinases ; Liver ; MAP kinase ; mitogen-activated protein kinase ; Neurodegenerative diseases ; Protein kinase ; Tumor necrosis factor-α ; Western blotting ; γ-Interferon</subject><ispartof>Pharmaceutical biology, 2022-12, Vol.60 (1), p.1169-1176</ispartof><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. 2022</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. 2022 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-fb8320383dcba7433a9cb53e878655cb62763eae66a73430ec4ed5e39d0e362f3</citedby><cites>FETCH-LOGICAL-c562t-fb8320383dcba7433a9cb53e878655cb62763eae66a73430ec4ed5e39d0e362f3</cites><orcidid>0000-0001-7700-8041 ; 0000-0002-0035-148X ; 0000-0003-0483-2480</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225694/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225694/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27481,27903,27904,53769,53771,59119,59120</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35701112$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Beilei</creatorcontrib><creatorcontrib>Mao, Yicheng</creatorcontrib><creatorcontrib>Chang, Lingling</creatorcontrib><creatorcontrib>Dai, Tao</creatorcontrib><creatorcontrib>Xin, Xiaoming</creatorcontrib><creatorcontrib>Ma, Fenfen</creatorcontrib><creatorcontrib>Wang, Zhijun</creatorcontrib><creatorcontrib>Shen, Zhuqing</creatorcontrib><creatorcontrib>Mei, Qibing</creatorcontrib><creatorcontrib>Zhu, Yizhun</creatorcontrib><title>S-Propargyl-cysteine prevents concanavalin A-induced immunological liver injury in mice</title><title>Pharmaceutical biology</title><addtitle>Pharm Biol</addtitle><description>S-Propargyl-cysteine (SPRC), an endogenous H 2 S modulator, exerts anti-inflammatory effects on cardiovascular and neurodegenerative disease, but it remains unknown whether SPRC can prevent autoimmune hepatitis. 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Mechanistically, SPRC increased H 2 S level (p &lt; 0.05) and promoted cystathionine γ-lyase (CSE) expression (p &lt; 0.05). SPRC inhibited the MAPK pathway activation and the apoptosis pathway. All the effects of SPRC were blocked by the CSE inhibitor PAG. SPRC prevents Con A-induced liver injury in mice by promoting CSE expression and producing endogenous H 2 S. 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To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury and uncover the underlying mechanisms. Mice were randomly divided into five groups: control, Con A, SPRC (5 and 10 mg/kg injected intravenously once a day for 7 days), and propargylglycine (PAG; 50 mg/kg injected intraperitoneally 0.5 h before SPRC for 7 days). All mice except the controls were intravenously injected with Con A (20 mg/kg) on day 7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using kits. Inflammatory cytokines (TNF-α and IFN-γ) in the blood and in the liver were detected by ELISA Kit and real-time PCR, respectively. The expression of mitogen-activated protein kinase (MAPK) pathway proteins (p-JNK and p-Akt) and apoptosis proteins (Bax and Bcl-2) was detected using western blotting. SPRC reduced the levels of AST (p &lt; 0.05) and ALT (p &lt; 0.01) and decreased the release of the inflammatory cytokines. Mechanistically, SPRC increased H 2 S level (p &lt; 0.05) and promoted cystathionine γ-lyase (CSE) expression (p &lt; 0.05). SPRC inhibited the MAPK pathway activation and the apoptosis pathway. All the effects of SPRC were blocked by the CSE inhibitor PAG. SPRC prevents Con A-induced liver injury in mice by promoting CSE expression and producing endogenous H 2 S. The mechanisms include reducing the release of inflammatory cytokines, attenuating MAPK pathway activation, and alleviating apoptosis.</abstract><cop>England</cop><pub>Taylor &amp; Francis</pub><pmid>35701112</pmid><doi>10.1080/13880209.2022.2080234</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-7700-8041</orcidid><orcidid>https://orcid.org/0000-0002-0035-148X</orcidid><orcidid>https://orcid.org/0000-0003-0483-2480</orcidid><oa>free_for_read</oa></addata></record>
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subjects AKT protein
Alanine transaminase
Apoptosis
Aspartate aminotransferase
autoimmune hepatitis
BAX protein
Bcl-2 protein
Concanavalin A
Cystathionine g-lyase
cystathionine γ-lyase
Cysteine
Cytokines
Enzyme-linked immunosorbent assay
Hepatitis
Hydrogen sulfide
Hydrogen sulphide
Inflammation
Kinases
Liver
MAP kinase
mitogen-activated protein kinase
Neurodegenerative diseases
Protein kinase
Tumor necrosis factor-α
Western blotting
γ-Interferon
title S-Propargyl-cysteine prevents concanavalin A-induced immunological liver injury in mice
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