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Chloroquine ameliorates hind‐limb ischemia/reperfusion‐induced remote hepatic injury via attenuating p38‐Mapk/NF‐κB p65 cue
Author(s) -
Sherif Miar,
Gad Amany,
Fawzy Hala,
ElAbhar Hanan,
Abdallah Dalaal
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01872
Subject(s) - hindlimb , medicine , pharmacology , chloroquine , p38 mitogen activated protein kinases , inflammation , reperfusion injury , ischemia , tumor necrosis factor alpha , mapk/erk pathway , nitric oxide , immunology , kinase , chemistry , biochemistry , malaria
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.