title: Penehyclidine Hydrochloride Pretreatment Ameliorates Rhabdomyolysis-Induced AKI by Activating the Nrf2/HO-1 Pathway and Alleviating [corrected] Endoplasmic Reticulum Stress in Rats. The.
abstract: Acute kidney injury (AKI) is one of the most severe complications of rhabdomyolysis (RM). The underlying mechanisms and potential preventions need to be investigated. Penehyclidine hydrochloride (PHC) was reported to ameliorate renal ischemia-reperfusion injury, but the effect of PHC on RM-reduced AKI is unknown. In this study, we established a rat model of RM-induced AKI using an intramuscular glycerol injection in the hind limbs. Rats were pretreated with PHC before the glycerol injection, and the heme oxygenase-1 (HO-1) inhibitor ZnPP was introduced to evaluate the effect of HO-1 on RM-induced AKI. PHC pretreatment ameliorated the pathological renal injury and renal dysfunction, and decreased the renal apoptosis rate in RM-induced AKI. PHC significantly up-regulated HO-1 expression, increased HO-1 enzymatic activity and decreased the accumulation of myoglobin in renal tissues. This effect was partly inhibited by ZnPP. PHC pretreatment also effectively up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) and down-regulated glucose regulated protein 78 (GRP78) and caspase-12 at both the gene and protein levels. These results suggest that the protective effects of PHC pretreatment on RM-induced AKI occur at least in part through activating the Nrf2/HO-1 pathway and alleviating endoplasmic reticulum stress (ERS) in rat renal tissues.
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Beijing, the People's Republic of China.|Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: XuDong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: LiXia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: XinJun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: LiHui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: YunShuang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: JingHua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province, the People's Republic of China.
authors.forename: GuangLi
authors.initials: G
authors.lastname: Wu
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D011812:Quinuclidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012206:Rhabdomyolysis / Q000150:complications*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018680:Cholinergic Antagonists; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D011812:Quinuclidines; C486140:penehyclidine; D051547:Heme Oxygenase-1