Measurement and meaning of markers of reactive species of oxygen, nitrogen and sulfur in healthy human subjects and patients with inflammatory joint disease

Abstract

<jats:p>Reactive species of oxygen, nitrogen and sulfur play cell signalling roles in human health, e.g. recent studies have shown that increased dietary nitrate, which is a source of RNS (reactive nitrogen species), lowers resting blood pressure and the oxygen cost of exercise. In such studies, plasma nitrite and nitrate are readily determined by chemiluminescence. At sites of inflammation, such as the joints of RA (rheumatoid arthritis) patients, the generation of ROS (reactive oxygen species) and RNS overwhelms antioxidant defences and one consequence is oxidative/nitrative damage to proteins. For example, in the inflamed joint, increased RNS-mediated protein damage has been detected in the form of a biomarker, 3-nitrotyrosine, by immunohistochemistry, Western blotting, ELISAs and MS. In addition to NO•, another cell-signalling gas produced in the inflamed joint is H2S (hydrogen sulfide), an RSS (reactive sulfur species). This gas is generated by inflammatory induction of H2S-synthesizing enzymes. Using zinc-trap spectrophotometry, we detected high (micromolar) concentrations of H2S in RA synovial fluid and levels correlated with clinical scores of inflammation and disease activity. What might be the consequences of the inflammatory generation of reactive species? Effects on inflammatory cell-signalling pathways certainly appear to be crucial, but in the current review we highlight the concept that ROS/RNS-mediated protein damage creates neoepitopes, resulting in autoantibody formation against proteins, e.g. type-II collagen and the complement component, C1q. These autoantibodies have been detected in inflammatory autoimmune diseases.</jats:p>

Tolerancia oral en artritis experimental inducida por antígeno en conejos por administración de hidrolizado de cartílago articular

“…El curso clínico de la AR es extremadamente variable, mostrando un amplio espectro de manifestaciones clínicas desde una enfermedad leve y autolimitada hasta una rápidamente progresiva con inflamación, destrucción de la articulación y discapacidad física severa 2 . La patobiología de la AR involucra varias poblaciones celulares como linfocitos T, B, macrófagos y fibroblastos, así como una compleja interacción de citoquinas proinflamatorias, que incluye óxido nítrico (NO) y, más específicamente, interferón ␥ (INF-␥), interleukina 2 (IL-2) y factor de necrosis tumoral ␣ (TNF-␣) y genera a nivel histológico un infiltrado muy importante de linfocitos y plasmocitos, con angiogénesis importante [3][4][5][6] .…”

Application of Fullerenes in Nanomedicine: An Update

“…However, it is a highly sensitive process and, when unbalanced, leads to the generation of free radicals or ROS, which have been proposed as being the mechanism underlying many chronic human diseases, including MC activation and inflammatory arthritis [47] . Fullerenes can be specifically designed to target and accumulate in the internal mitochondrial membrane bilayers.…”

Role of reactive oxygen and nitrogen species in formation of acute and chronic experimental arthritis

“…Характерною ознакою РА є запальні процеси у суглобах і супутніх тканинах, що визначає важ-кість перебігу цього захворювання [17]. Відомо, що у розвиток запалення залучені оксидативні процеси за участю активних форм оксигену (АФО) й активних форм нітрогену (АФН) [10,18]. Для вивчення механізмів розвитку ревматоїдного артриту широко використовують експериментальні моделі у щурів [8,13].…”