Protective effect of fatty acid amide hydrolase inhibitor URB597 and monoacylglycerol lipase inhibitor KML29 on renal ischemia-reperfusion injury via toll-like receptor 4/nuclear factor-kappa B pathway

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dc.authoridCakir, Murat/0000-0002-2066-829X
dc.authoridAydin, Ali/0000-0002-9550-9111
dc.authorwosidCakir, Murat/I-8643-2019
dc.authorwosidAydin, Ali/ACM-7774-2022
dc.contributor.authorCakir, Murat
dc.contributor.authorAydin, Ali
dc.contributor.authorTekin, Suat
dc.date.accessioned2024-08-04T20:53:16Z
dc.date.available2024-08-04T20:53:16Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground: Arachidonoyl ethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) are the most studies endocannabinoids. AEA and 2-AG are degraded by fatty acid amide hydrolase (FAAH) and mono-acylglycerol lipase (MAGL) enzymes, respectively. FAAH and MAGL enzymes are widely expressed in many tissues, including kidney. Recent works have depicted that AEA and 2-AG levels are associated with ische-mia-reperfusion (IR) injury. In this study, we investigated the effects of MAGL inhibitor KML29 and FAAH in-hibitor URB597 against kidney IR injury.Methods: The kidneys of the rats underwent ischemia for 45 min and then reperfusion for 24 h. KML29 and URB597 were administered intraperitoneally with kidney IR to two different treatment groups. Results: IR application increased serum blood urea nitrogen (BUN), creatinine (Cre), interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels, while these parameters were decreased following KML29 and URB597 administration. KML29 and URB597 administration also reduced the increased toll-like receptor-4 (TRL-4), phosphorylated-NF-kappa B, phosphorylated-I kappa B-alpha, tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1 beta), interleukin-6 (IL-6), caspase-3 levels and histopatho-logical damage in kidney tissue.Conclusions: Our results reveal that MAGL inhibitor KML29 and FAAH inhibitor URB597 have a protective effect on kidney IR injury by preventing apoptosis and inflammation. Inhibition of MAGL and FAAH may be a new therapeutic strategy to prevent kidney IR injury.en_US
dc.description.sponsorshipDepartment of Scientific ResearchProjects of Bozok University [6602c-TF/20-353]en_US
dc.description.sponsorshipFunding This study was supported by the Department of Scientific ResearchProjects of Bozok University (Project no: 6602c-TF/20-353) .en_US
dc.identifier.doi10.1016/j.intimp.2022.109586
dc.identifier.issn1567-5769
dc.identifier.issn1878-1705
dc.identifier.pmid36700769en_US
dc.identifier.scopus2-s2.0-85144468226en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.intimp.2022.109586
dc.identifier.urihttps://hdl.handle.net/11616/101072
dc.identifier.volume114en_US
dc.identifier.wosWOS:000968076600001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofInternational Immunopharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectIschemia-reperfusion injuryen_US
dc.subjectKidneyen_US
dc.subjectFatty acid amide hydrolaseen_US
dc.subjectMonoacylglycerol lipaseen_US
dc.subjectKML29en_US
dc.subjectURB597en_US
dc.titleProtective effect of fatty acid amide hydrolase inhibitor URB597 and monoacylglycerol lipase inhibitor KML29 on renal ischemia-reperfusion injury via toll-like receptor 4/nuclear factor-kappa B pathwayen_US
dc.typeArticleen_US

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