Probucol attenuates lipopolysaccharide-induced leukocyte recruitment and inflammatory hyperalgesia: effect on NF-кB activation and cytokine production

European Journal of Pharmacology
Amanda Z ZucolotoWaldiceu A Verri

Abstract

Probucol 4,4'- (Isopropylidenedithio)bis(2,6-di-tert-butylphenol) is a synthetic molecule clinically used for prevention and treatment of hypercholesterolemia and atherosclerosis. Recent studies have shown that the beneficial effects of probucol mainly derive from its anti-inflammatory and antioxidant properties. Gram-negative bacteria are common infectious agents and their wall components, e.g. lipopolysaccharide (LPS), are important elicitors of inflammation. LPS is sensed by tissue resident cells and it triggers a Toll-like receptor 4/MyD88-dependent signaling cascade resulting in endothelial activation, leukocyte recruitment and nociception. Therefore the present study aimed to investigate the anti-inflammatory and analgesic effects of probucol in models of LPS-induced acute inflammation. Probucol at 0.3-30mg/kg was administrated to male Swiss mice per oral 1h before intraplantar or intraperitoneal lipopolysaccharide stimulus. Probucol at 3mg/kg reduced lipopolysaccharide-induced mechanical and thermal hyperalgesia. These effects were accompanied by reduced leukocyte influx and cytokine production in both paw skin and peritoneum exudate. Unexpectedly, probucol did not alter lipopolysaccharide-induced tissue oxidative stress...Continue Reading

References

Jul 21, 1999·Kidney International. Supplement·M OzakiW Sakamoto

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Citations

Sep 19, 2018·Free Radical Research·Paul R J AmesJose DelgadoAlves
Sep 7, 2018·Neural Plasticity·Cristine de Paula Nascimento-CastroPatricia S Brocardo
Apr 28, 2020·Journal of Atherosclerosis and Thrombosis·Shizuya YamashitaUNKNOWN PROSPECTIVE Study Group
Apr 17, 2021·Bioorganic & Medicinal Chemistry Letters·Dilidaer AjiaikebaierJingya Li
Oct 16, 2021·Experimental and Therapeutic Medicine·Eun Ji YeoSoo Young Choi

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