title: Chronic nicotine exposure exacerbates acute renal ischemic injury.
abstract: Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.
authors.affiliation: Dept. of Pediatrics, Div. of Pediatric Nephrology, University of Mississippi Medical Center, Research Wing Rm. R127, 2500 N. State St., Jackson, MS 39216, USA. iarany@umc.edu
authors.forename: Istvan
authors.initials: I
authors.lastname: Arany
authors.forename: Samira
authors.initials: S
authors.lastname: Grifoni
authors.forename: Jeb S
authors.initials: JS
authors.lastname: Clark
authors.forename: Eva
authors.initials: E
authors.lastname: Csongradi
authors.forename: Christine
authors.initials: C
authors.lastname: Maric
authors.forename: Luis A
authors.initials: LA
authors.lastname: Juncos
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003367:Cotinine / Q000097:blood / Q000378:metabolism; D007511:Ischemia / Q000473:pathology*; D007668:Kidney / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects; D008156:Luciferases / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000235:genetics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology
chemical_list: D018722:Nicotinic Agonists; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D008315:Malondialdehyde; D009538:Nicotine; D008156:Luciferases; D048670:MAP Kinase Kinase 4; D003367:Cotinine