Anti-inflammatory effects of oral and intraperitoneal administration of cerium oxide nanoparticles on experimental hepatic ischemia-reperfusion injury
Akile Zengin1
, Açelya Erikçi2, Gökçen Telli3, Bülent Gümüşel4, Kemal Kösemehmetoğlu5, Gülberk Uçar6, Mustafa Cem Algın7
1Clinic of Gastrointestinal Surgery, Malatya Training and Research Hospital, Malatya, Türkiye
2Department of Biochemistry, Lokman Hekim University Faculty of Pharmacy, Ankara, Türkiye
3Department of Pharmacology, Hacettepe University Faculty of Pharmacy, Ankara, Türkiye
4Department of Pharmacology, Lokman Hekim University Faculty of Pharmacy, Ankara, Türkiye
5Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Türkiye
6Department of Biochemistry, Hacettepe University Faculty of Pharmacy, Ankara, Türkiye
7Department of General Surgery, Kütahya Health Science University, Kütahya, Türkiye
Abstract
Objective: Hepatic ischemia-reperfusion (IR) injury occurs in liver surgery, resection, and transplantation. Reactive oxygen species (ROS) produced following IR starts the cascade of cell damage, necrosis/apoptosis, and proinflammatory responses by activating intracellular signaling cascade to drive hepatocellular damage. Cerium oxide nanoparticles (CONPs) act as anti-inflammatory and antioxidant agents. Thus, we evaluated the protective effects of oral (o.g.) and intraperitoneal (i.p.) administration of CONPs on hepatic IR injury.
Material and Methods: Mice were randomly divided into five groups: control, sham, IR protocol, CONP+IR (i.p.), and CONP+IR (o.g.). Mouse hepatic IR protocol was applied to the animals in the IR group. CONPs (300 μg/kg) were administered 24 hours before IR protocol. Blood and tissue samples were taken after the reperfusion period.
Results: Hepatic IR injury markedly increased enzyme activities, tissue lipid peroxidation, myeloperoxidase (MPO), xanthine oxidase (XO), nitrite oxide (NO), and tissue nuclear factor kappa-B (NF-κB) p65 levels, plasma pro-inflammatory cytokines, chemokines, and adhesion molecules while decreasing antioxidant markers and caused pathological changes in hepatic tissue. The expression of tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2), and 9 increased, and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) expression decreased in the IR group. Pretreatment with CONPs o.g. and i.p. 24 hours before hepatic ischemia improved the biochemical parameters above and alleviated the histopathological findings.
Conclusion: Results of the present study demonstrate a significant reduction in liver degeneration by administering CONPs via i.p. and o.g. route in an experimental liver IR model, suggesting that CONPs have the extensive potential to prevent hepatic IR injury.
Keywords: Ischemia reperfusion, cerium oxide nanoparticles (CONPs), mouse, oxidative stress, inflammation
Cite this article as: Zengin A, Erikçi A, Telli G, Gümüşel B, Kösemehmetoğlu K, Uçar G, et al. Anti-inflammatory effects of oral and intraperitoneal administration of cerium oxide nanoparticles on experimental hepatic ischemiareperfusion injury. Turk J Surg 2022; 38 (3): 255-265.
The approval for this study was obtained from Dumlupınar University Animal Experiments Local Ethics Committee with the Decision no: 2017.04-02, Date: 06.04.2017).
Externally peer-reviewed.
Concept – A.Z., A.E., G.T.; Design – A.Z., A.E., G.T.; Supervision – G.U., M.C.A., B.G.; Materials – A.Z., A.E., G.T.; Data Collection and/ or Processing – K.K., G.T.; Analysis and/or Interpretation – G.U., M.C.A., B.G.; Literature Search – A.Z., K.K.; Writing Manuscript – A.Z., G.U., K.K.; Critical Reviews – G.U., M.C.A., B.G.
The authors have no conflicts of interest to declare.
The authors declared that this study has received no financial support.