Octreotide and melatonin alleviate inflammasome-induced pyroptosis through inhibiting TLR4-NF- κB-NLRP3 pathway in hepatic ischemia/reperfusion injury.

Octreotide and melatonin alleviate inflammasome-induced pyroptosis through inhibiting TLR4-NF-κB-NLRP3 pathway in hepatic ischemia/reperfusion injury. Toxicol Appl Pharmacol. 2020 Nov 29;:115340 Authors: El-Sisi AEE, Sokar SS, Shebl AM, Mohamed DZ, Abu-Risha SE Abstract BACKGROUND AND AIM: The Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway is essential in the pathogenesis of hepatic ischemia/ reperfusion (HIR) injury. Pyroptosis is a proinflammatory programmed cell death that is related to several diseases. Thus, the purpose of this study was to examine whether pretreatment with octreotide (somatostatin analogue, OCT) at different doses or OCT at 75 μg/kg combined with melatonin (N-acetyl-5-methoxytryptamine, MLT) could produce hepatic protection against HIR injury. METHODS: Rats were randomized into sham, HIR, OCT (50, 75, and 100 μg/kg, respectively), MLT, and MLT + OCT75 groups. Ischemia was induced for 30 min followed by 24 h reperfusion. RESULTS: OCT pretreatment at doses (50 or 75 μg/kg), MLT alone, and MLT + OCT75 significantly ameliorated the biochemical with histopathological changes, oxidative stress, inflammation, apoptosis, then augmented anti-oxidant and anti-apoptotic markers with downregulation of HMGB1, TLR4, MyD88, TRAF-6, p-IκBα (S32), p-NF-κBp65 (S536), NLRP3, ASC, caspase-1(p20), and GSDMD-N expressions compared with HIR group. Lastly, Octreot...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research