title: Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats.
abstract: Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-кB(NF-кB) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-κB, tumor necrosis factor-α, and interleukin-1β levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-κB, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using α2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-κB pathway activation. The renoprotective effects are related to α2A-adrenergic receptor subtypes.
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Department of Anesthesiology, Guangzhou, 510630, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Department of Anesthesiology, Guangzhou, 510630, China.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Department of Pathology, Guangzhou, 510630, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Department of Anesthesiology, Guangzhou, 510630, China.|The First Affiliated Hospital, University of South China, Department of Anesthesiology, Hengyang, 421001, China.
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Department of Anesthesiology, Guangzhou, 510630, China.
authors.forename: Pinjie
authors.initials: P
authors.lastname: Huang
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Department of Anesthesiology, Guangzhou, 510630, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Li Ka Shing Faculty of Medicine, University of Hong Kong, Department of Anesthesiology, 21 Sassoon Road, Hong Kong SAR, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Department of Anesthesiology, Guangzhou, 510630, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001806:Blood Urea Nitrogen; D002460:Cell Line; D003404:Creatinine / Q000097:blood; D020927:Dexmedetomidine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D018613:Microscopy, Confocal; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D018341:Receptors, Adrenergic, alpha-2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D020927:Dexmedetomidine; D003404:Creatinine