title: Acetaminophen attenuates obesity-related renal injury through ER-mediated stress mechanisms.
abstract: OBJECTIVE
  Obesity is an independent risk factor for the development of kidney disease. The purpose of this study was to determine how obesity may contribute to renal damage and whether acetaminophen ingestion can diminish obesity-associated renal cell injury in the obese Zucker rat model.
  
  
  METHODS
  Male obese Zucker rats (4 weeks old, n=6) were treated with acetaminophen (30 mg / kg body weight / day) for 26 weeks. Age matched obese control (OC), obese vehicle (OV, 0.073 mL DMSO/kg/d), and lean Zucker rats (LC) were used to determine the effects of treatment and obesity.
  
  
  RESULTS
  Compared to lean control rats, renal lipid deposition, expression of the endoplasmic reticulum (ER) stress protein GRP78 and activation of the ER stress-related eIF2α-ATF4-CHOP, caspase 12, and JNK-MAPK signaling pathways were increased in the obese control and obese vehicle rats. These alterations were associated with the elevated renal cell apoptosis and urinary albumin excretion. Acetaminophen treatment decreased renal lipid deposition, ER-stress related signaling, apoptosis and albuminuria.
  
  
  CONCLUSIONS
  These data suggest that the protective effects of low dose acetaminophen on renal injury are mediated, at least in part, through attenuation of ER stress.
authors.affiliation: Center for Diagnostic Nanosystems, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
authors.forename: Cuifen
authors.initials: C
authors.lastname: Wang
authors.forename: Miaozong
authors.initials: M
authors.lastname: Wu
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Arvapalli
authors.forename: Xiaoniu
authors.initials: X
authors.lastname: Dai
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mahmood
authors.forename: Henry
authors.initials: H
authors.lastname: Driscoll
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.forename: Eric
authors.initials: E
authors.lastname: Blough
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000419:Albuminuria; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000082:Acetaminophen; D051701:Activating Transcription Factor 4; D018712:Analgesics, Non-Narcotic; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; C497110:Atf4 protein, rat; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP