RESUMO
Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress.
Assuntos
Doxiciclina/química , Sequestradores de Radicais Livres/química , Sistema Livre de Células , Doxiciclina/farmacologia , Sequestradores de Radicais Livres/farmacologia , Células HEK293 , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Malondialdeído/química , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxidos/química , Superóxidos/metabolismoRESUMO
On January 26, 2018, the 23rd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado. The meeting consisted of plenary sessions with oral presentations and a poster presentation session. There were four plenary sessions that covered a wide range of topics relating to alcohol use: Alcohol and Liver Disease; Alcohol, Inflammation and Immune Response; Alcohol and Organ Injury; Heath Consequences and Alcohol Drinking. The meeting provided a forum for the presentation and discussion of novel research findings regarding alcohol use and immunology.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Alcoolismo/imunologia , Pesquisa Biomédica/tendências , Congressos como Assunto/tendências , Imunidade Celular/imunologia , Consumo de Bebidas Alcoólicas/patologia , Alcoolismo/diagnóstico , Animais , Pesquisa Biomédica/métodos , Colorado , Humanos , Imunidade Celular/efeitos dos fármacosRESUMO
OBJECTIVE: To compare anti-malondialdehyde-acetaldehyde (MAA) antibody concentrations between rheumatoid arthritis (RA) patients and healthy and rheumatic disease controls. METHODS: Anti-MAA antibody (IgA, IgM, IgG) was measured using ELISA and banked serum from patients with RA (nâ¯=â¯284), osteoarthritis (OA, nâ¯=â¯330), spondyloarthropathy (SpA, nâ¯=â¯50), and systemic lupus erythematosus (SLE, nâ¯=â¯88) as well as healthy controls (nâ¯=â¯82). Anti-MAA antibody concentrations and the frequency of positivity were compared across groups. Multivariable linear regression analysis limited to RA and OA patients (due to sample size and data availability) was used to identify factors associated with anti-MAA antibody concentrations. RESULTS: Although RA patients demonstrated among the highest circulating concentrations across isotypes, only IgA anti-MAA antibody was significantly higher than all other groups (pâ¯≤â¯0.02). Proportions (7% to 74%) of OA and SLE (less so for SpA) samples were positive for anti-MAA antibody, limiting the discriminatory capacity of anti-MAA antibody in RA (positive in 18% to 80%). In analyses limited to those with RA or OA, factors associated with higher anti-MAA antibody concentrations included RA case status, younger age (IgM), male sex (IgG), African American race (IgA, IgG) and current smoking (IgA). C-reactive protein levels and comorbidities were not associated with anti-MAA antibody concentrations. CONCLUSION: With the possible exception of the IgA isotype, serum anti-MAA antibodies measured with currently available assays do not appear to adequately discriminate RA from other rheumatic conditions. With the identification of specific proteins that are MAA-modified in diseased tissues and requisite assay refinement, anti-MAA antibody holds potential promise as a biomarker in RA.