title: Propofol pretreatment attenuates remote kidney injury induced by orthotopic liver autotransplantation, which is correlated with the activation of Nrf2 in rats.
abstract: Nuclear factor erythroid 2‑related factor 2 (Nrf2) is a critical regulator of the cellular‑defense response in protection against oxidative injury. Several studies have demonstrated that propofol ameliorates ischemia/reperfusion injury in a number of organs. However, whether propofol exerts renal protection against liver transplantation via Nrf2 activation remains to be elucidated. The aim of the present study was to investigate the effects of orthotopic liver autotransplantation (OLAT) on renal Nrf2 expression and to determine whether propofol protects against kidney injury induced by OLAT via Nrf2 activation. A total of 24 male Sprague Dawley rats were randomly divided into four groups: sham surgery + normal saline (sham group); OLAT + normal saline (OLAT group); OLAT + propofol 50 mg/kg (L‑Prop group) and OLAT + propofol 100 mg/kg (H‑Prop group). Normal saline and propofol were administered for 3 consecutive days through an intraperitoneal injection prior to surgery. Kidney pathology, blood urea nitrogen (BUN), creatinine (Cr), superoxide anion (O2•‑), hydroxyl radical (·OH), maleic dialdehyde (MDA) and expression levels of Nrf2, Kelch‑like ECH‑associated protein 1 (Keap1), heme oxygenase‑1 (HO‑1) and NADP quinine oxidoreductase 1 (NQO1) were assessed 8 h after OLAT. It was demonstrated that OLAT induced remote kidney damage. Pretreatment with propofol significantly ameliorated renal pathology and abrogated the increase of the Cr and BUN concentrations, O2•‑ and ·OH activities, and MDA levels induced by OLAT. In the H‑Prop group, Keap1 expression in the cytoplasm was decreased and Nrf2 expression in the nucleus was upregulated, accompanied by an increase of HO‑1 and NQO1 expression. The present results suggest that propofol pretreatment exerted renal protection against OLAT, with the upregulation of nuclear Nrf2 expression as a potential mechanism.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Mian
authors.initials: M
authors.lastname: Ge
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Chenfang
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D017382:Reactive Oxygen Species; D003404:Creatinine; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D015742:Propofol