Colchicine attenuates renal ischemia-reperfusion-induced liver damage: implication of TLR4/NF-κB, TGF-β, and BAX and Bcl-2 gene expression

Abstract

Ischemia-reperfusion injury (IRI) is typically associated with a vigorous inflammatory and oxidative stress response to hypoxia and reperfusion that disturbs the function of the organ. The remote effects of renal IRI on the liver, however, require further study. Renal damage associated with liver disease is a common clinical problem. Colchicine, a polymerization inhibitor of microtubules, has been used as an anti-inflammatory and anti-fibrotic drug for liver diseases. The goal of the current study was to investigate the possible protective mechanisms of colchicine on liver injury following renal IRI. Forty rats were divided randomly into four groups: sham group, colchicine-treated group, IRI group, and colchicine-treated + IRI group. Treatment with colchicine significantly reduced hepatic toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) transcription factor, myeloid differentiation factor 88 (MyD88), and tumor necrosis factor-alpha (TNF-α) contents; downregulated BCL2 associated X apoptosis regulator (BAX) gene expression, transforming growth factor-β (TGF-β) content, and upregulated hepatic B cell lymphoma 2 (Bcl-2) gene expression as compared with the IRI group. Finally, hepatic histopathological examinations have confirmed the biochemical results. Renal IRI-induced liver damage in rats was alleviated by colchicine through its anti-inflammatory, anti-apoptotic, and anti-fibrotic actions.

Ramelteon attenuates renal ischemia and reperfusion injury through reducing mitochondrial fission and fusion and inflammation

“…This result elucidates that ramelteon alleviates IRI by mitigating the inflammatory response. TLR4 is involved in the pathophysiology of inflammation and AKI induced by renal IRI ( 36 ). Yang et al showed that MT promotes autophagy and ameliorates renal IRI though TLR4/MyD88/MEK/ERK/mTORC1 ( 37 ).…”

Study on the mechanism of action of colchicine in the treatment of coronary artery disease based on network pharmacology and molecular docking technology

“…Colchicine gel was reported to inhibit myocardial apoptosis and fibrosis in mice with myocardial infarction and improved cardiac function and structure ( Chen et al, 2020 ). Colchicine exerts its anti-inflammatory, anti-apoptotic and anti-fibrotic effects through upregulated hepatic B-cell lymphoma 2 (Bcl-2) and downregulated Bcl-2 associated X protein (BAX) expression and transforming growth factor-β (TGF-β) content, which attenuates rat liver injury induced by renal ischemia-reperfusion injury ( Awad et al, 2022 ). It was shown that when cytochrome C is released from mitochondria, it activates the caspase-3 apoptotic pathway and promotes cardiomyocyte apoptosis, making cardiac function impaired ( Radhakrishnan et al, 2007 ).…”

Technologies for Solubility, Dissolution and Permeation Enhancement of Natural Compounds

“…Moreover, Gasparyan et al (2015) [151] and Paré et al (2020) [152] reported an enhanced anti-inflammatory activity associated with colchicine. Furthermore Casanova et al (2015) stated that colchicine may also be used against various cardiovascular disorders [223] and recently Awad et al (2022) revealed an enhanced healing of damaged liver through colchicine [153].…”