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

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Abstract

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.

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Funding

This research project was supported by a grant from the Research Center of the Female Scientific and Medical Colleges, Deanship of Scientific Research, King Saud University, Saudi Arabia.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Manal H. Al-dossari, Laila M. Fadda, Hala A. Attia & Iman H. Hasan

  2. Department of Biochemistry, College of Pharmacy, Mansoura University, Mansoura, Egypt

    Hala A. Attia

  3. Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt

    Ayman M. Mahmoud

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  1. Manal H. Al-dossari
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  2. Laila M. Fadda
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  3. Hala A. Attia
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  4. Iman H. Hasan
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  5. Ayman M. Mahmoud
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Correspondence to Ayman M. Mahmoud.

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The experimental protocol and all animal procedures were approved by the Institutional Animal Ethics Committee of King Saud University (IRB NO. KSU-SE-19-06).

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Al-dossari, M.H., Fadda, L.M., Attia, H.A. et al. Curcumin and Selenium Prevent Lipopolysaccharide/Diclofenac-Induced Liver Injury by Suppressing Inflammation and Oxidative Stress. Biol Trace Elem Res 196, 173–183 (2020). https://doi.org/10.1007/s12011-019-01910-4

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