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NFR2 EXPRESSION IN APAP ACUTE INTOXICATION
Author(s) -
Cardoso João Felipe Rito,
Cohen Célia,
Vannucchi Hélio
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb441
Subject(s) - glutathione , acetaminophen , oxidative stress , chemistry , gene expression , gclc , pharmacology , antioxidant , necrosis , medicine , enzyme , biochemistry , gene
Acetaminophen (APAP) overdose promotes the formation of NAPQI, the depletion of liver glutathione and oxidative stress. N‐acetilcysteine (NAC) is a cysteine donator that is a precursor for the synthesis of GSH. Nrf2 is a transcription factor, important in antioxidant response pathway, promoting the expression of phase II enzyme and the regulation of liver GSH. Male C57 mices, were fasted for 16h prior to the application of APAP (250mg/kg). The treatment with NAC (204mg/kg) occurred 1h after APAP challenge. The collection of liver tissue occurred 24h after treatment. Analysis: Histopathology by score of necrosis fields; hepatic levels of GSH by spectrophotometry and hepatic levels of Vitamin E (VE) by HPLC; the gene expression of NFR2 by RT‐qPCR (Taqman probes). Statistic Analysis: Student. t test (Graphpad Prism 5.0). The group (ANAC) that received treatment with NAC 1h after APAP challenge, showed a reduction of 28% of necrosis (p <0.05). ANAC GSH levels were 1.5 higher than the APAP levels (p <0.05), although VE presents no differences between the groups. The Nfr2 gene expression fold change had almost doubled compared with APAP group (p <0.05). The results show that after the treatment with NAC, the increase of NFR2 gene expression promotes the increase of GSH levels, saving the reduction of VE and consequently, the oxidative stress, protecting the liver from necrosis. Support by FAPESP (2011/12749–0 & 2011/17616–9)