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Chloroquine ameliorates hind‐limb ischemia/reperfusion‐induced remote hepatic injury via attenuating p38‐Mapk/NF‐κB p65 cue

2021; Wiley; Volume: 35; Issue: S1 Linguagem: Inglês

10.1096/fasebj.2021.35.s1.01872

1530-6860

Miar M. Sherif, Amany M. Gad, Hala M. Fawzy, Hanan S. El‐Abhar, Dalaal M. Abdallah,

Cell death mechanisms and regulation

Lower limb ischemia-reperfusion (I/R) injury elicits systemic inflammation associated with multiple organ dysfunctions, a series of organ damage different from the initial insult. Chloroquine is an antimalarial drug that has been repurposed to manage a plethora of diseases, among which is rheumatoid arthritis, lupus erythematosus, and more recently Covide-19 based on its potent anti-inflammatory potential. This study aimed to investigate the effect of chloroquine as a treatment for the remote liver injury triggered by the hind-limb I/R insult. The experiment was conducted on three groups divided into control, hind-limb I/R induced by applying orthodontics rubber bands to one hind-limb for one and half hours followed by reperfusion for seven days, and chloroquine post-hind-limb I/R administration for seven days. Chloroquine protected the liver against the hind-limb I/R injury evident by decreasing the serum levels of the aminotransferases (ALT & AST) and deactivating the hepatic p38 mitogen-activated protein kinase (MAPK)/ nuclear factor (NF)-κB p65 cue to inhibit tumor necrosis factor-α with the elevation of interleukin-10 to verify its anti-inflammatory effect. Additionally, it readjusted redox imbalance indicated by the inhibition of nitric oxide, 8-hydroxy 2 deoxyguanosine, and malondialdehyde versus enhancing the total anti-oxidant capacity; also, the drug reduced caspase-3 and LC3 II. Accordingly, the present study showed that the chloroquine attenuates the hind-limb I/R-induced liver injury via its anti-inflammatory, anti-oxidant, and anti-apoptotic potentials mainly by deactivating the hepatic p38/p65 cue.