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Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway
Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamid...
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Published in: | Scientific reports 2021-06, Vol.11 (1), p.12296 |
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description | Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-β1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling. |
doi_str_mv | 10.1038/s41598-021-91666-6 |
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Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-β1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling.</description><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-021-91666-6</identifier><identifier>PMID: 34112866</identifier><language>eng</language><publisher>England: Nature Publishing Group UK</publisher><subject>Actins - genetics ; Animals ; Antioxidants - pharmacology ; Caspase 3 - genetics ; Gene Expression Regulation - drug effects ; Humans ; Liver Cirrhosis - chemically induced ; Liver Cirrhosis - drug therapy ; Liver Cirrhosis - genetics ; Liver Cirrhosis - pathology ; Lymphocyte Antigen 96 - genetics ; Molecular Docking Simulation ; NF-kappa B - genetics ; Protein Binding - drug effects ; Rats ; Serum Albumin - drug effects ; Signal Transduction - drug effects ; Taurine - genetics ; Taurine - pharmacology ; Thioacetamide - toxicity ; Toll-Like Receptor 4 - genetics</subject><ispartof>Scientific reports, 2021-06, Vol.11 (1), p.12296</ispartof><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-4309-7095</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/PMC8192756/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192756/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34112866$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Younis, Nancy S</creatorcontrib><creatorcontrib>Ghanim, Amal M H</creatorcontrib><creatorcontrib>Elmorsy, Mohammad A</creatorcontrib><creatorcontrib>Metwaly, Heba A</creatorcontrib><title>Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><description>Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-β1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling.</description><subject>Actins - genetics</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Caspase 3 - genetics</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Liver Cirrhosis - chemically induced</subject><subject>Liver Cirrhosis - drug therapy</subject><subject>Liver Cirrhosis - genetics</subject><subject>Liver Cirrhosis - pathology</subject><subject>Lymphocyte Antigen 96 - genetics</subject><subject>Molecular Docking Simulation</subject><subject>NF-kappa B - genetics</subject><subject>Protein Binding - drug effects</subject><subject>Rats</subject><subject>Serum Albumin - drug effects</subject><subject>Signal Transduction - drug effects</subject><subject>Taurine - genetics</subject><subject>Taurine - pharmacology</subject><subject>Thioacetamide - toxicity</subject><subject>Toll-Like Receptor 4 - genetics</subject><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpVkMlOwzAQhi0kRKvSF-CA_AKhcbw0viBBxSZV4lLO0cSxW1MnjmynqG_BIxPEIpjLjP7lOwxCFyS_IjktF5ERLsssL0gmiRAiEydoWuSMZwUtigmax_iaj8MLyYg8QxPKCClKIabofQNDsJ3G0GpnfYCkI04760HpBK1tNLZdMyjdYGcPOmBj6-CjjaOMx3TEBwu49c3gIFnfYW9w8s6N6b3GQSvdJx8wW3SDchrGPqhPYQ99D_gWR7vtwNlui3tIuzc4nqNTAy7q-feeoZf7u83qMVs_PzytbtZZT0meMsMbw3JBNSGcG6YMGS-xNEIZw7gEJQjQ0VWqlI1gBjitQZckN1JKVTM6Q9df3H6oW90o3aUAruqDbSEcKw-2-u90dldt_aEqiSyWXIyAy7-A3-bPb-kHdheAZQ</recordid><startdate>20210610</startdate><enddate>20210610</enddate><creator>Younis, Nancy S</creator><creator>Ghanim, Amal M H</creator><creator>Elmorsy, Mohammad A</creator><creator>Metwaly, Heba A</creator><general>Nature Publishing Group UK</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4309-7095</orcidid></search><sort><creationdate>20210610</creationdate><title>Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway</title><author>Younis, Nancy S ; Ghanim, Amal M H ; Elmorsy, Mohammad A ; Metwaly, Heba A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p310t-f5df4063e1155f4cf1e1167f6cff459ac61a33e1cc89d64fa53bae810f999cb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Actins - genetics</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Caspase 3 - genetics</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humans</topic><topic>Liver Cirrhosis - chemically induced</topic><topic>Liver Cirrhosis - drug therapy</topic><topic>Liver Cirrhosis - genetics</topic><topic>Liver Cirrhosis - pathology</topic><topic>Lymphocyte Antigen 96 - genetics</topic><topic>Molecular Docking Simulation</topic><topic>NF-kappa B - genetics</topic><topic>Protein Binding - drug effects</topic><topic>Rats</topic><topic>Serum Albumin - drug effects</topic><topic>Signal Transduction - drug effects</topic><topic>Taurine - genetics</topic><topic>Taurine - pharmacology</topic><topic>Thioacetamide - toxicity</topic><topic>Toll-Like Receptor 4 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Younis, Nancy S</creatorcontrib><creatorcontrib>Ghanim, Amal M H</creatorcontrib><creatorcontrib>Elmorsy, Mohammad A</creatorcontrib><creatorcontrib>Metwaly, Heba A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Younis, Nancy S</au><au>Ghanim, Amal M H</au><au>Elmorsy, Mohammad A</au><au>Metwaly, Heba A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway</atitle><jtitle>Scientific reports</jtitle><addtitle>Sci Rep</addtitle><date>2021-06-10</date><risdate>2021</risdate><volume>11</volume><issue>1</issue><spage>12296</spage><pages>12296-</pages><eissn>2045-2322</eissn><abstract>Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-β1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling.</abstract><cop>England</cop><pub>Nature Publishing Group UK</pub><pmid>34112866</pmid><doi>10.1038/s41598-021-91666-6</doi><orcidid>https://orcid.org/0000-0003-4309-7095</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Actins - genetics Animals Antioxidants - pharmacology Caspase 3 - genetics Gene Expression Regulation - drug effects Humans Liver Cirrhosis - chemically induced Liver Cirrhosis - drug therapy Liver Cirrhosis - genetics Liver Cirrhosis - pathology Lymphocyte Antigen 96 - genetics Molecular Docking Simulation NF-kappa B - genetics Protein Binding - drug effects Rats Serum Albumin - drug effects Signal Transduction - drug effects Taurine - genetics Taurine - pharmacology Thioacetamide - toxicity Toll-Like Receptor 4 - genetics |
title | Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway |
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