Curcumin and Selenium Prevent Lipopolysaccharide/Diclofenac-Induced Liver Injury by Suppressing Inflammation and Oxidative Stress

• Published in: Biological trace element research 2020-07, Vol.196 (1), p.173-183
• Main Authors: Al-dossari, Manal H., Fadda, Laila M., Attia, Hala A., Hasan, Iman H., Mahmoud, Ayman M.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; Antioxidants; Biochemistry; Biomarkers - analysis; Biomarkers - metabolism; Biomedical and Life Sciences; Biotechnology; C-reactive protein; Chemical and Drug Induced Liver Injury, Chronic - drug therapy; Chemical and Drug Induced Liver Injury, Chronic - metabolism; Chemical and Drug Induced Liver Injury, Chronic - pathology; Curcumin; Curcumin - administration & dosage; Curcumin - pharmacology; Cytokines; Diclofenac; Diclofenac - administration & dosage; Diclofenac - antagonists & inhibitors; Diclofenac - pharmacology; Drug dosages; Drugs; Glutathione; Heme; Heme oxygenase (decyclizing); Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Injections, Intravenous; Injury prevention; Intravenous administration; Life Sciences; Lipid peroxidation; Lipids; Lipopolysaccharides; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Liver; Male; NF-κB protein; Nitric oxide; Nonsteroidal anti-inflammatory drugs; Nutrition; Oncology; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Oxygenase; Peroxidation; Rats; Rats, Wistar; Selenium; Selenium - administration & dosage; Selenium - pharmacology; Serum; Superoxide dismutase; TLR4 protein; Toll-like receptors
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-019-01910-4

Diclofenac (DCL), an anti-inflammatory drug used to reduce pain and inflammation, ranks in the top causes of drug-induced liver injury. The inflammatory stress induced by inflammagens is implicated in DCL-induced liver injury. Curcumin (CUR) and selenium (Se) possess anti-inflammatory effects; therefore, this study evaluated their protective potential against lipopolysaccharide (LPS)/DCL-induced liver injury. Rats received CUR and/or Se for 7 days followed by a single intravenous administration of LPS 2 h before a single injection of DCL and two other doses of CUR and/or Se 2 and 8 h after DCL. Administration of nontoxic doses of LPS and DCL resulted in liver damage evidenced by the significantly elevated liver function markers in serum. LPS/DCL-induced liver injury was confirmed by histological alterations, increased lipid peroxidation and nitric oxide, and diminished glutathione and superoxide dismutase. CUR and/or Se prevented liver injury, histological alterations, and oxidative stress and boosted antioxidant defenses in LPS/DCL-induced rats. In addition, CUR and/or Se reduced serum C-reactive protein, liver pro-inflammatory cytokines, and the expression of TLR4, NF-κB, JNK, and p38, and upregulated heme oxygenase-1 (HO-1). In conclusion, CUR and/or Se mitigated LPS/DCL-induced liver injury in rats by suppressing TLR4 signaling, inflammation, and oxidative stress and boosting HO-1 and other antioxidants. Therefore, CUR and Se can hinder the progression and severity of liver injury during acute inflammatory episodes.