TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis
Objective(s): Acute kidney injury (AKI) is a major component of isoproterenol (ISO) induced cardiorenal syndrome. In this study, we investigated the effect of TLR4‐IN‐C34 as a toll-like receptor (TLR)-4 inhibitor on ameliorating ISO-induced AKI and the possible molecular underlying pathways. Materia...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2022-11-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_21157_ce4a41b7831aa4ec8af6e22372edf164.pdf |
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| author | Hadeer Abdelsalam Manar Helal Nashwa Abu-Elsaad |
| author_facet | Hadeer Abdelsalam Manar Helal Nashwa Abu-Elsaad |
| author_sort | Hadeer Abdelsalam |
| collection | DOAJ |
| description | Objective(s): Acute kidney injury (AKI) is a major component of isoproterenol (ISO) induced cardiorenal syndrome. In this study, we investigated the effect of TLR4‐IN‐C34 as a toll-like receptor (TLR)-4 inhibitor on ameliorating ISO-induced AKI and the possible molecular underlying pathways. Materials and Methods: The study included 4 groups: control group, ISO group (rats received 100 mg/kg ISO in 2 doses 24 hr apart, SC), ISO+C341 and ISO+C343 groups (rats received 1 or 3 mg/kg TLR4‐IN‐C34 respectively twice one hour before each ISO injection, IP). Results: Obtained results showed that TLR4‐IN‐C34 injection prior to ISO decreased serum creatinine level (P<0.05). Renal tissue histopathologic changes were markedly decreased by TLR4‐IN‐C34. Renal relative expression of MAPK and MyD88 mRNA decreased significantly in both ISO+C341 and ISO+C343 groups compared with the ISO group (P<0.05). Furthermore, TLR-IN-C34 lowered the inflammatory cytokines IL-8, IL-1β, and IL-12 renal levels (P<0.05). Immunostained kidney sections showed a marked decrease in NF-κb positive cells in addition to the apoptotic marker Bax (P<0.05) by the two tested doses of TLR4‐IN‐C34. On the other hand, the expression of the antiapoptotic marker Bcl-2 by renal cells was markedly increased. Conclusion: It can be concluded that TLR4-IN-C34 ameliorates ISO-induced AKI through anti-inflammatory anti-apoptotic effects and modulation of TLR4 signaling pathways. |
| first_indexed | 2024-04-13T17:29:23Z |
| format | Article |
| id | doaj.art-37c932b0b1ff456ab8e9d869717acb36 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-04-13T17:29:23Z |
| publishDate | 2022-11-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-37c932b0b1ff456ab8e9d869717acb362022-12-22T02:37:37ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-11-0125111334134010.22038/ijbms.2022.67168.1472721157TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosisHadeer Abdelsalam0Manar Helal1Nashwa Abu-Elsaad2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptObjective(s): Acute kidney injury (AKI) is a major component of isoproterenol (ISO) induced cardiorenal syndrome. In this study, we investigated the effect of TLR4‐IN‐C34 as a toll-like receptor (TLR)-4 inhibitor on ameliorating ISO-induced AKI and the possible molecular underlying pathways. Materials and Methods: The study included 4 groups: control group, ISO group (rats received 100 mg/kg ISO in 2 doses 24 hr apart, SC), ISO+C341 and ISO+C343 groups (rats received 1 or 3 mg/kg TLR4‐IN‐C34 respectively twice one hour before each ISO injection, IP). Results: Obtained results showed that TLR4‐IN‐C34 injection prior to ISO decreased serum creatinine level (P<0.05). Renal tissue histopathologic changes were markedly decreased by TLR4‐IN‐C34. Renal relative expression of MAPK and MyD88 mRNA decreased significantly in both ISO+C341 and ISO+C343 groups compared with the ISO group (P<0.05). Furthermore, TLR-IN-C34 lowered the inflammatory cytokines IL-8, IL-1β, and IL-12 renal levels (P<0.05). Immunostained kidney sections showed a marked decrease in NF-κb positive cells in addition to the apoptotic marker Bax (P<0.05) by the two tested doses of TLR4‐IN‐C34. On the other hand, the expression of the antiapoptotic marker Bcl-2 by renal cells was markedly increased. Conclusion: It can be concluded that TLR4-IN-C34 ameliorates ISO-induced AKI through anti-inflammatory anti-apoptotic effects and modulation of TLR4 signaling pathways.https://ijbms.mums.ac.ir/article_21157_ce4a41b7831aa4ec8af6e22372edf164.pdfapoptosisisoproterenolmapkmyd88nf-kappa btoll-like receptor |
| spellingShingle | Hadeer Abdelsalam Manar Helal Nashwa Abu-Elsaad TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis Iranian Journal of Basic Medical Sciences apoptosis isoproterenol mapk myd88 nf-kappa b toll-like receptor |
| title | TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis |
| title_full | TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis |
| title_fullStr | TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis |
| title_full_unstemmed | TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis |
| title_short | TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis |
| title_sort | tlr4 in c34 protects against acute kidney injury via modulating tlr4 myd88 nf κb axis mapk and apoptosis |
| topic | apoptosis isoproterenol mapk myd88 nf-kappa b toll-like receptor |
| url | https://ijbms.mums.ac.ir/article_21157_ce4a41b7831aa4ec8af6e22372edf164.pdf |
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