RESUMO
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-ß (TGF-ß) 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.
Assuntos
Colchicina/farmacologia , Colchicina/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Nefropatias/tratamento farmacológico , Nefropatias/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Animais , Anti-Inflamatórios , Antifibróticos , Apoptose/efeitos dos fármacos , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologiaRESUMO
Ischemia-reperfusion injury (IRI) induces an inflammatory response and production of reactive oxygen species, which affects the organs remote to the sites of renal IR. However, remote effects of renal IRI on the liver need further investigations. Renal injury associated with liver disease is a common clinical problem. Colchicine is an established drug for microtubule stabilization that may reduce tissue injury and has antioxidant and antiinflammatory effects. The aim of the present study was (i) to assess the hepatic changes after induction of renal IRI, (ii) to explore the possible protective effect of colchicine on liver injury following renal IRI, and (iii) to investigate the possible mechanisms underlying the potential effect. Forty rats were randomly divided into four groups: sham operation group, colchicine-treated group, IR group, and colchicine-treated IR group. Colchicine treatment improved liver function (ALT/AST) after renal IRI, decreased hepatic oxidative stress and cell apoptosis by reducing hepatic MDA, upregulating hepatic total antioxidant capacity, Nrf2, and HO-1. Furthermore, colchicine inhibited inflammatory responses by downregulating hepatic NLRP3 inflammasome, IL-1ß, and caspase-1. Colchicine attenuates renal IRI-induced liver injury in rats. This effect may be due to reducing inflammation and oxidative stress markers.
