Modulatory effect of zingerone against cisplatin or γ-irradiation induced hepatotoxicity by molecular targeting regulation

• Published in: Applied radiation and isotopes 2019-12, Vol.154, p.108891, Article 108891
• Main Authors: Mohamed, Hebatallah E., Badawy, Monda M.M.
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Alkaline Phosphatase - blood; Animals; Aspartate Aminotransferases - blood; Cisplatin; Cisplatin - antagonists & inhibitors; Cisplatin - toxicity; CYP2E1; Cytochrome P-450 CYP2E1 - genetics; Gamma Rays - adverse effects; Gene Expression - drug effects; Gene Expression - radiation effects; Guaiacol - administration & dosage; Guaiacol - analogs & derivatives; Guaiacol - pharmacology; Hepatotoxicity; Inflammation Mediators - metabolism; Liver - drug effects; Liver - metabolism; Liver - radiation effects; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - radiation effects; MAPK; Molecular Targeted Therapy; Protective Agents - administration & dosage; Protective Agents - pharmacology; Radiation-Protective Agents - administration & dosage; Radiation-Protective Agents - pharmacology; Rats; TLR4; Zingerone; γ-Irradiation
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2019.108891

Zingerone (ZO) is an ingredient of ginger (Zingiber officinale) which has different pharmacological properties. The objective of this research was to evaluate the protective effect of ZO against Cisplatin (Cis) or γ-Irradiation (IR)-induced hepatotoxicity in rats. ZO was given orally for consecutive 14 days prior to the treatment with Cis or exposure to IR at 15th day. Animals were sacrificed at the 23rd day. Cis or IR induced a marked increase in MAPK signal transduction as evidenced by increased p38 MAPK, JNK and ErK1/2. CYP2E1 and NADPH oxidase were significantly up-regulated. Inflammatory markers (TLR4, iNOS, COX-2 and MPO) and liver enzymes (AST, ALT and ALP) activities were also increased. Administration of ZO significantly ameliorated the above mentioned parameters. •Cis or IR induced a marked increase in MAPK signal transduction, CYP2E1 and NADPH oxidase, Inflammatory markers and liver enzymes activities.•ZO treatment markedly improved the Cis or IR induced hepatotoxicity.•ZO may be beneficial for minimize the side effects of Cis or IR therapy.