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Therapeutic potential of carfilzomib, an irreversible proteasome inhibitor, against acetaminophen‐induced hepatotoxicity in mice
Author(s) -
Alanazi Abdulrazaq,
Algfeley Saleh G.,
AlHosaini Khaled A.,
Korashy Hesham M.,
Imam Faisal,
Nagi Mahmoud N.
Publication year - 2017
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.21877
Subject(s) - acetaminophen , pharmacology , carfilzomib , oxidative stress , proteasome inhibitor , glutathione , tumor necrosis factor alpha , intraperitoneal injection , chemistry , reactive oxygen species , liver injury , medicine , proteasome , enzyme , biochemistry
Overdose of acetaminophen (APAP) is often associated with hepatotoxicity. Carfilzomib (CFZ) shows multiple pharmacological activities including anti‐inflammatory potential. Therefore, this study was undertaken to evaluate the possible therapeutic effects of CFZ against APAP‐induced hepatotoxicity. Hepatotoxicity was induced by administration of APAP (350 mg/kg, intraperitoneal). Mice were given CFZ (0.125, 0.25, or 0.5 mg/kg, intraperitoneal) 1.5 h after APAP administration. Animals were sacrificed on 6 h and blood and liver tissue samples were collected for analysis. In CFZ‐post‐treated group, there was significant and dose‐dependent decrease in serum alanine aminotransferase levels. The level of tumor necrosis factor‐α (TNF‐α), reactive oxygen species, and NO decreased, whereas glutathione increased significantly by CFZ post‐treatment. Upregulated mRNA expression of COX‐II and iNOS were significantly downregulated by CFZ post‐treatment. CFZ may exert its hepatoprotective action by alleviating inflammatory, oxidative, and nitrosative stress via inhibition of TNF‐α, COX‐II, and iNOS.