Effect of acute Atorvastatin treatment in an experimental model of colitis

Abstract

Acute atorvastatin treatment in an experimental model of colitis was studied using the acetic acid induction modality for colitis in rats. This study was aimed to evaluate possible therapeutic effects of atorvastatin against acetic acid-induced colitis in a rat model and to find out the correlation between severity index with oxidative stress parameters and inflammatory markers. Experimental colitis was induced in rats by rectal administration of 4% acetic acid (vol/vol). Rats with colitis were received either atorvastatin 10mg/kg or sulfasalazine 100mg/kg orally for 7 days. Macroscopical and microscopical assessment and the measurement of the colonic cytokines (IL-6 and TNF-α), oxidative stress markers; myeloperoxidase (MPO) and malondialdehyde (MDA), and adhesion molecules (E-Selectin and ICAM-1). Both the macroscopical lesion area and histological colonic injury induced by acetic acid were reduced significantly by both atorvastatin and sulfasalazine. These were associated by attenuation of the increased colonic MPO activity, MDA and proinflammatory cytokines. In addition, there is the downregulation of the adhesion molecules. In the present study, Atorvastatin had shown therapeutic effects in experimental colitis. The anti-inflammatory actions involve antioxidant effect related to phenolic moiety along with inhibition of adhesion molecule synthesis in the colonic tissues.

Atorvastatin improves intestinal mucositis induced by 5-fluorouracil in mice by modulating the and epithelial barrier and inflammatory signaling pathways

“…Treatment with 10 mg/kg ATV in this study reduced the scores and delayed the onset of diarrhea. Similarly, other studies using rosuvastatin, simvastatin, and ATV in colitis models have demonstrated a reduction in the disease activity index (22,46,47).…”

Therapeutic effects and the impact of statins in the prevention of ulcerative colitis in preclinical models: A systematic review

“…In addition, statins have been highlighted in reducing lipid peroxidation. This effect was also observed in the studies analyzed, 25,27,30,35,36,39,40 which described the reduction in Malondialdehyde (MDA) and 2‐thiobarbituric acid (TBA) In experimental UC, MDA is generally increased Oxygen radicals produce membrane peroxidation and MDA formation, which are detrimental to cell function 100–102 . However, statins have stood out in reducing MDA 99,103 …”

“…They are quickly mobilized to the infection sites and exert their defenses against microorganisms through phagocytosis and the release of soluble and protein antimicrobial compounds 76 . Usually, high levels of MPO are found in IBD, and among the studies analyzed, all detected an increase in the levels of this enzyme in animals with UC 25,27,35,40,41,77 . Statins have been reported to reduce mRNA levels of the MPO gene by 20‐ to 200‐fold in monocyte–macrophage and bone marrow precursors 78 .…”

“…76 Usually, high levels of MPO are found in IBD, and among the studies analyzed, all detected an increase in the levels of this enzyme in animals with UC. 25,27,35,40,41,77 Statins have been reported to reduce mRNA levels of the MPO gene by 20-to 200-fold in monocyte-macrophage and bone marrow precursors. 78 Statins block MPO expression by inhibiting the production of isoprenoid intermediates, including GPP, in the HMG-CoA pathway.…”