الفهرس | Only 14 pages are availabe for public view |
Abstract Zymosan (ZYM), a natural compound, provokes acute peritonitis and multiple organ dysfunction that affects the kidney, beside other organs via exaggerated inflammatory response. The aim of the present study is to test the role of cholinergic anti-inflammatory pathway (CAP) in alleviating acute kidney injury (AKI) induced by ZYM in BALB/c mice, using galantamine (GAL), a cholinesterase inhibitor.This agent is able to activate Ü7nicotinic acetylcholine receptor (nAChR) to stimulate CAP. GAL verified its anti-inflammatory effect by elevating acetylcholine level with abating the interleukin (IL)-6/Janus kinase 2 (Y1007/1008)/signal transducer and activator of transcription 3 (Y705) inflammatory axis, with a consequent inhibition in suppressor of cytokine signaling 3. These effects repressed also the high mobility group box protein-1/ nuclear factor-kappa B (p65) signaling pathway. Furthermore, the reno-protective effect of Ü7nAChR agonist was associated by reduction in plasma creatinine, cystatin-C, IL-18, and renal neutrophil gelatinase-associated lipocalin, as well as kidney injury molecule in parallel to improved kidney architecture deteriorated by sterile sepsis. Blocking the Ü7nAChR by methyllycaconitine abolished the beneficial effects of GAL to document the involvement of this receptor and the CAP in the amelioration of AKI induced by ZYM |