Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model

Abstract

AIMTo evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model.METHODSAn acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured.RESULTSIn DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05).CONCLUSIONRosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease.

Protective Effect of Iridoid Glycosides of the Leaves of Syringa oblata Lindl. on Dextran Sulfate Sodium-Induced Ulcerative Colitis by Inhibition of the TLR2/4/MyD88/NF-κB Signaling Pathway

“…DSS is a chemical colitogen with anticoagulant properties that induce damage in the epithelial monolayer lining in the intestine, leading to the dissemination of proinflammatory intestinal contents including ROS production, bloody diarrhea, weight loss, colon shortening, and mucosal ulceration [5,19]. Hence, DSS-induced colitis models are commonly used to study for IBD.…”

“…Although the exact pathogenesis of UC has not been ascertained up to now, the abnormal mucosal immunity and colonic inflammation have been demonstrated to be major mechanisms involved in the pathophysiology of UC [3,4]. The abnormal activity of the host immune system and inflammatory response are predominantly characterized by increased production of proinflammatory cytokines and the activation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [5,6]. In this regard, modulation of both abnormal mucosal immunity and inflammatory response could be an important therapeutic modality for UC.…”

“…Specially, the expression of NOX1 in human colonic epithelial cells is higher, and lymphocytes in lesions of CD and UC showed high levels of NOX1 expression [13]. In addition, oxidative stress contributes to the accumulation of oxidative damage products in the colon tissue such as 8-hydroxydeoxyguanosine (8-OHdG) [5]. Recent studies reveal that toll-like receptors (TLRs), such as TLR2, TLR4, and TLR6, are activated in the progression of UC [14].…”

“…BioMed Research International proinflammatory cytokines, such as interleukin-(IL-) 2, IL-4, IL-5, IL-12p40, and IL-13 [5,15]. Therefore, targeted inhibition of TLRs/MyD88/NF-κB by removal or deactivation of inflammatory mediators and oxidative stress could be an important protective and therapeutic treatment for UC.…”

Effect of rosuvastatin combined with trimetazidine on the cardiac function in the treatment of patients with coronary heart disease

“…The muscle contraction energy, growth of the heart, metabolism, and all the substances required for physiological activity are supplied by a blood vessel deriving from the aortic root. Clinical practice has shown that the inflammatory response plays a significant role in the pathogenesis of coronary heart disease, such as lymphocytes and granulocytes, which can help the patients with coronary heart disease [7]. Previous studies on coronary heart disease have found that the relationship between the cardiovascular disease and endothelial function is increasingly getting closer, which can aggravate the damage degree of vascular endothelial function to a certain extent and then aggravate the patient's condition.…”