A3 adenosine receptor agonist, CF102, protects against hepatic ischemia/reperfusion injury following partial hepatectomy.
Ischemia/reperfusion (IR) injury during clinical hepatic procedures is characterized by inflammatory conditions and the apoptosis of hepatocytes. Nuclear factor‑κB (NF‑κB), nitric oxide and the expression levels of inflammatory cytokines, tumor necrosis factor‑α and interleukin‑1 were observed to increase following IR and mediate the inflammatory response in the liver. CF102 is a highly selective A3 adenosine receptor (A3AR) agonist, and has been identified to induce an anti‑inflammatory and protective effect on the liver via the downregulation of the NF‑κB signaling pathway. The present study aimed to determine the effect of CF102 on protecting the liver against IR injury. The potential protective effect of CF102 (100 µg/kg) was assessed using an IR injury model on 70% of the liver of Wistar rats, which was induced by clamping the hepatic vasculature for 30 min. The regenerative effect of CF102 was assessed by the partial hepatectomy of 70% of the liver during 10 min of IR. CF102 reduced the levels of liver enzymes following IR injury. A higher regeneration rate in the CF102 treatment group was observed compared with the control group, suggesting that CF102 had a positive effect on the proliferation of hepatocytes following hepatectomy. CF102 had a protective effect on the liver of Wistar rats subsequent to IR injury during hepatectomy. This may be due to an anti‑inflammatory and anti‑apoptotic effect mediated by the A3AR.
Department of Surgery A/B, Rabin Medical Center, Campus Golda, Sackler Faculty of Medicine Tel‑Aviv University, Petah Tikva 49100, Israel.
Gil
G
Ohana
Can‑Fite BioPharma, Ltd., Kiryat‑Matalon, Petah Tikva 49170, Israel.
Shira
S
Cohen
Department of Pathology, Rabin Medical Center, Campus Golda, Sackler Faculty of Medicine Tel‑Aviv University, Petah Tikva 49100, Israel.
Lea
L
Rath-Wolfson
Can‑Fite BioPharma, Ltd., Kiryat‑Matalon, Petah Tikva 49170, Israel.
Pnina
P
Fishman
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058909:Adenosine A3 Receptor Agonists / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D058909:Adenosine A3 Receptor Agonists; D043684:Receptor, Adenosine A3; D014409:Tumor Necrosis Factor-alpha; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide