title: Contribution of PPARγ in modulation of acrolein-induced inflammatory signaling in gp91phoxknock-out mice.
abstract: Oxidative stress and inflammation are major contributors to acrolein toxicity. Peroxisome proliferator activated receptor gamma (PPARγ) has antioxidant and anti-inflammatory effects. We investigated the contribution of PPARγ ligand GW1929 to the attenuation of oxidative stress in acrolein-induced insult. Male gp91phoxknock-out (KO) mice were treated with acrolein (0.5 mg·(kg body mass)-1by intraperitoneal injection for 7 days) with or without GW1929 (GW; 0.5 mg·(kg body mass)-1·day-1, orally, for 10 days). The livers were processed for further analyses. Acrolein significantly increased 8-isoprostane and reduced PPARγ activity (P < 0.05) in the wild type (WT) and KO mice. GW1929 reduced 8-isoprostane (by 32% and 40% in WT and KO mice, respectively) and increased PPARγ activity (by 81% and 92% in WT and KO, respectively). Chemokine activity was increased (by 63%) in acrolein-treated WT mice, and was reduced by GW1929 (by 65%). KO mice exhibited higher xanthine oxidase (XO). Acrolein increased XO and COX in WT mice and XO in KO mice. GW1929 significantly reduced COX in WT and KO mice and reduced XO in KO mice. Acrolein significantly reduced the total antioxidant status in WT and KO mice (P < 0.05), which was improved by GW1929 (by 75% and 74%). The levels of NF-κB were higher in acrolein-treated WT mice. GW1929 reduced NF-κB levels (by 51%) in KO mice. Acrolein increased CD36 in KO mice (by 43%), which was blunted with GW1929. Data confirms that the generation of free radicals by acrolein is mainly through NAD(P)H, but other oxygenates play a role too. GW1929 may alleviate the toxicity of acrolein by attenuating NF-κB, COX, and CD36.
authors.affiliation: a College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA.
authors.forename: Zivar
authors.initials: Z
authors.lastname: Yousefipour
authors.affiliation: b College of Pharmacy, Chicago State University, Chicago, IL 60503, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Chug
authors.affiliation: b College of Pharmacy, Chicago State University, Chicago, IL 60503, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Marek
authors.affiliation: b College of Pharmacy, Chicago State University, Chicago, IL 60503, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Nesbary
authors.affiliation: a College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mathew
authors.affiliation: a College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA.
authors.forename: Kasturi
authors.initials: K
authors.lastname: Ranganna
authors.affiliation: b College of Pharmacy, Chicago State University, Chicago, IL 60503, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Newaz
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D047495:PPAR gamma; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D000171:Acrolein
keywords: GW1929; NAD(P)H; PPARγ; acrolein; inflammatory signaling; signalisation inflammatoire