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Lophirones B and C halt acetaminophen hepatotoxicity by upregulating redox transcription factor Nrf‐2 through Akt, PI3K, and PKC pathways
Author(s) -
Aliyu Najeeb O.,
AjalaLawal Rafiat A.,
Ajiboye Taofeek O.
Publication year - 2018
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22055
Subject(s) - acetaminophen , protein kinase b , pi3k/akt/mtor pathway , protein kinase c , chemistry , liver injury , pharmacology , oxidative stress , kinase , phosphorylation , biochemistry , signal transduction , medicine
We investigated the mechanism of lophirones B‐ and C‐mediated protection against acetaminophen hepatotoxicity. Mice were pretreated with 20 mg/kg body weight lophirones B and C for 7 days and challenged with acetaminophen on day 7. Acetaminophen raised nuclear factor‐κB (NF‐κB) in the liver of mice but lowered protein kinase B (Akt). Although, acetaminophen produced no significant alteration on nuclear erythroid related factor‐2 (Nrf‐2), phosphoinositide 3‐kinase (PI3K) and protein kinase C (PKC), lophirones B and C raised the level of these proteins and Akt. The acetaminophen‐mediated increase in NF‐κB was significantly reversed by lophirones B and C. Lophirones B and C prevented acetaminophen‐mediated alterations in serum biomarkers of hepatic injury. Similarly, lophirones B and C lowered the biomarkers of oxidative stress in the liver of acetaminophen‐treated mice. It can be inferred from this study that lophirones B and C prevent acetaminophen‐induced liver injury by enhancing Nrf‐2 through Akt, PI3K, and PKC pathways.