Oxidative stress induced by Cremophor EL is not accompanied by changes in NF-kappaB activation or iNOS expression.
The effects of polyoxyethylenglycerol triricinoleate 35 (Cremophor EL, CrEL) on markers of oxidative stress, nuclear factor kappa B (NF-kappaB) activation and inducible nitric oxide synthase (iNOS) expression were studied in the liver of male Wistar rats. Animals were randomly divided into three groups. Group Cr1 received, i.p., CrEL at 0.046ml/kg daily for 7 days, group Cr2 received CrEL at 0.33ml/kg and the controls were injected with CrEL vehicle (saline solution with 25% ethanol). Both alanine transaminase (ALT) and aspartate transaminase (AST) serum activities were significantly increased in the Cr2 group (+16% and +25%, respectively). AST activity was also higher in the Cr1 group when compared to control animals (+20%). The cytosolic concentration of thiobarbituric acid reactive substances (TBARS) increased in both groups of rats receiving CrEL (Cr1: +24%; Cr2: +33%). Reduced glutathione (GSH) concentration was not significantly modified at any of the CrEL doses, but both the hepatic concentration of oxidised glutathione (GSSG) (Cr1: +37%; Cr2: +84%) and the GSH/GSSG ratio (Cr1: -21%; Cr2: -45%) were significantly modified. CrEL induced no significant NF-kappaB activation, changes in p50 and p65 NF-kappaB subunits or induction of iNOS protein. Data obtained indicate that although high doses of CrEL cause oxidative stress, this is not enough to induce changes in NF-kappaB activation or iNOS expression.
Department of Physiology, University of León, 24071 León, Spain.
María Belén
MB
Gutiérrez
Beatriz San
BS
Miguel
Carmen
C
Villares
Javier González
JG
Gallego
María Jesús
MJ
Tuñón
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives* / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D014677:Pharmaceutical Vehicles / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016328:NF-kappa B; D014677:Pharmaceutical Vehicles; D017392:Thiobarbituric Acid Reactive Substances; C000515:cremophor EL; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D005990:Glycerol; D019803:Glutathione Disulfide