Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice

Abstract

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 μL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

Streptococcus thermophilus Attenuates Inflammation in Septic Mice Mediated by Gut Microbiota

“…Tissue slides were stained with hematoxylin and eosin (H&E) for histological analysis. The histopathologic scores of different tissues were evaluated through different scores systems ( Gloor et al, 2000 ; Ji et al, 2018 ; Ko et al, 2020 ; Yang et al, 2020 ).…”

Resistance exercise improves short-term memory through inactivation of NF-κB pathway in mice with Parkinson disease

“…The enzyme-linked immunoassay for TNF-α, IL-6, and IL-1β in the hippocampus was done using enzyme immunoassay kit (Abcam, Cambridge, UK) as written below ( Ko et al, 2020 ).…”

“…Inflammatory cells produced tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the secretion of these proinflammatory cytokines was enhanced by nuclear factor (NF)-κB activation ( Wang et al, 2019 ). Overproduction of TNF-α, IL-1β, and IL-6 exacerbated the progress of acute liver injury ( Ko et al, 2020 ), and thus inhibition of proinflammatory cytokines is presented as a guideline for the treatment of acute liver injury.…”

“…Inhibition on NF-κB suppressed inducible nitric oxide, cyclooxygenase 2, nitric oxide, and prostaglandin 2 (inflammatory mediators) expression and TNF-α, IL-6, and IL-1β (proinflammatory cytokines) production ( Subedi et al, 2019 ). CCl 4 injection induced liver damage by NF-κB activation through IkBα phosphorylation ( Ko et al, 2020 ). Voluntary wheel running effectively reduced the NF-κB pathway activated by brain inflammation ( Ko and Ko, 2020 ).…”

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“…Tissue slides were stained with hematoxylin and eosin (H&E) for histological analysis. The histopathologic scores of different tissues were evaluated through different scores systems (Gloor et al, 2000;Ji et al, 2018;Ko et al, 2020;Yang et al, 2020).…”