Suppression of inflammatory cascades via novel cinnamic acid nanoparticles in acute hepatitis rat model

• Published in: Archives of biochemistry and biophysics 2020-12, Vol.696, p.108658, Article 108658
• Main Authors: Ibrahim, Ehab A., Moawed, Fatma S.M., Moustafa, Enas M.
• Format: Article
• Language: English
• Subjects: Acute Disease; Acute hepatitis; animal models; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - therapeutic use; Anti-Inflammatory Agents - toxicity; antioxidant activity; antioxidants; Apoptosis; biophysics; blood serum; CANPs; caspase-1; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - pathology; Cinnamates - chemistry; Cinnamates - therapeutic use; Cinnamates - toxicity; cinnamic acid; Galactosamine; gamma radiation; Gamma Rays; gene expression; hepatitis; Hepatitis - drug therapy; Hepatitis - pathology; histology; inflammation; interleukin-18; liver; Liver - pathology; Liver - radiation effects; Male; malondialdehyde; nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Nanoparticles - toxicity; NF-κB; nitric oxide; NLRP3; oral administration; oxidation; Oxidative Stress - drug effects; pro-apoptotic proteins; protein synthesis; Proteins - metabolism; Rats, Sprague-Dawley; Signal Transduction - drug effects
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2020.108658

Hepatitis was characterized by extreme inflammation and hepatocellular damage. Therefore, the current study aimed to gain insights into the modulation role of Cinnamic acid nanoparticles (CANPs) against acute hepatitis induced by d-Galactosamine and gamma radiation exposure (D-Gal/radiation) in the rat model and to suggest the implied molecular mechanism of CANPs. Acute hepatitis seriousness and the serum enzyme activities of ALT, AST, and ALP have been diminished upon oral administration of CANPs. Besides, the hepatic tissue levels of malondialdehyde (MDA) and nitric oxide (NO) have been significantly decreased, and the total antioxidant activity (TAO) depletion was extremely restored. Furthermore, the reduction of hepatic damage caused by pretreatment with CANPs was accompanied by significant suppression in the levels of hepatic proinflammatory cytokines (TNF-α, IL-1β, and IL-18), NF-κB, NLRP3, caspase-1 and proapoptotic protein BAX whereas anti-apoptotic protein Bcl-2 level significantly elevated as compared with D-Gal/radiation-induced acute hepatitis (AH) group. Also, CANPs suppress the D-Gal/radiation-induced IL-1β, IL-18, and ASK1 mRNA gene expression and the protein expression of TLR4 and MyD88 in the hepatic tissue. These biochemical parameters are confirmed by histological examination of the liver tissues. The present results indicated that CANPs can protect the hepatic cells from damage by both its anti-inflammatory and antioxidant influence as well as by modulating oxidation cellular pathways that have contributed to the acute severity of hepatitis. Also, CANPs is capable of suppressing apoptosis. Consequently, Nanoparticles of Cinnamic acid have the medicinal ability to protect the liver from acute hepatitis. •D-Gal/radiation increased oxidative/nitrosative stress.•Liver dysfunction, due to the imbalance of oxidative stress and antioxidant.•ROS activated the NLRP3 inflammasome signaling pathway.•CANPs significantly corrected acute hepatitis.