Effects of statins on experimental colitis in normocholesterolemic rats.
OBJECTIVE
The results of previous studies suggest that statins have a direct anti-inflammatory effect that is not directly related to their cholesterol-lowering activity. The aim of this study was to investigate the effect of simvastatin (SIM) and fluvastatin (FLU) on trinitrobenzene sulfonic acid (TNBS)-induced colonic inflammation in rats.


METHODS
The drugs were given for 3 days (0.1 and 1 mg/kg day-1; intraperitoneally) after induction of colitis. The lesions in the distal colon were scored at the macroscopic and microscopic level. Tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were assessed and formation of reactive oxygen species and peroxynitrite was monitored by chemiluminescence (CL) assay. Trunk blood was collected for the measurement of serum tumor necrosis factor (TNF)-alpha level.


RESULTS
Treatment with SIM reduced the lesion score of the colitis group at macroscopic level (p<0.05), but there was no effect of treatment with FLU. The increase in colonic MDA level of the colitis group was reduced by both drugs at all doses (p<0.05-0.001). The decrease in GSH and the an increase in MPO activity in the colitis group were reversed by SIM at all doses (p<0.01), but FLU had no effect. An increase in colonic lucigenin CL value in the colitis group was reduced by SIM and FLU at all doses (p<0.001) and an increase in peroxynitrite ratio in the colitis group showed a significant reduction in SIM-treated groups; FLU reduced this effect at a dose of 1 mg/kg (p<0.01). An increase in tissue collagen content and serum TNF-alpha level in the colitis group was reversed by both drugs at all doses (p<0.001).


CONCLUSIONS
SIM and FLU seemed to be beneficial in a TNBS-induced rat colitis model through the prevention of lipid peroxidation, superoxide generation, cytokine production and neutrophil accumulation.
Jahovic
Nermina
N
Department of Physiology, Marmara University School of Medicine, and Kasimpaşa Military Hospital, Divison of Biochemistry, Haydarpaşa, Istanbul, Turkey.
Gedik
Nursal
N
Ercan
Feriha
F
Sirvanci
Serap
S
Yüksel
Meral
M
Sener
Göksel
G
Alican
Inci
I
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000032:analysis; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D000077340:Fluvastatin; D005978:Glutathione / Q000032:analysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use*; D049449:Luminescence; D008315:Malondialdehyde / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis; D019821:Simvastatin / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000077340:Fluvastatin; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D003094:Collagen; D002784:Cholesterol; D019821:Simvastatin; D009195:Peroxidase; D005978:Glutathione