Hepatoprotective Impact Of TLR9 Antagonist ODN 2088 Against Carbon Tetrachloride (CCl₄)-Induced Hepatic Injury

Abstract

The main objective of this study is to evaluate the hepatoprotective impact of TLR9 antagonist ODN 2088 against carbon tetrachloride (CCl 4)-induced acute liver injury. In this study, 24 mice were grouped into four groups. CCl 4 was introduced in all groups except for the control group intraperitoneally after pretreatment with ODN 2088 and silymarin for seven days. To assess the liver injury, serum alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) were estimated and histopathological changes in the liver tissue were investigated. Expression of pro-inflammatory cytokines including TNF-α and IL-6 were measured. It was observed that the serum levels of biochemical parameters such as ALT and AST were remarkably elevated in mice treated only with CCl 4 compared with the control mice (treated with corn oil). This increase in levels of ALT and AST was remarkably diminished by pretreatment with ODN 2088. The hepatoprotective impact of ODN 2088 on CCl 4-intoxicated mice was verified by histopathological studies. ODN2088 pretreatment inhibited liver inflammation by diminishing the liver expression of CCl 4-induced activity of TNF-α and IL-6. In conclusion, TLR9 antagonist, ODN 2088, protected the mice against CCl 4-induced liver damage and inflammation by down-regulating the expression of pro-inflammatory cytokines.

Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury

“…All these findings indicate that targeting TLRs could mitigate the clinical presentation, outcomes, and prognosis of COVID-19. ODN2088 is a murine TLR9 antagonist that has been shown to be potent in preventing hepatic inflammation and fibrosis in a CCl4-induced liver fibrosis mouse model [ 23 , 33 ]. In this study, we evaluated ODN2088 as a potential therapeutic agent for prevention of pulmonary injury, inflammation, and fibrosis.…”

“…The oligonucleotide ODN2088 (a DNA sequence) inhibits the activity of TLR9 and its downstream signaling effectors by disturbing the co-localization of unmethylated CpG di-nucleotides with TLR9 [ 22 ]. A previous study showed that ODN2088 inhibits the liver inflammation and fibrosis induced by CCl4 [ 23 ]. In the present study, a bleomycin-induced lung injury mouse model was used to evaluate the impact of TLR9 inhibition by ODN2088 on the lung damage, inflammation, and fibrosis commonly seen in ARDS in COVID-19 patients.…”