Effects of low-dose atorvastatin combined with reduced-dose prednisolone in acetic acid-induced ulcerative colitis in rats.

Long-term corticosteroid treatment for ulcerative colitis (UC) is often limited by dose-dependent adverse effects, highlighting the need for strategies that reduce steroid exposure. This study evaluated the efficacy of a combination of half-doses of Atorvastatin and Prednisolone in rats with acetic acid-induced colitis. Thirty-five rats were allocated to five groups (n = 7 per group): normal control, vehicle-treated UC control, UC treated with atorvastatin (10 mg/kg/day, orally), UC treated with prednisolone (10 mg/kg/day, orally), and UC treated with the combination of atorvastatin (5 mg/kg/day) plus prednisolone (5 mg/kg/day), orally. Treatment continued for 10 days. Disease activity index (DAI), colonic edema index, histopathological leukocyte infiltration, pro-inflammatory cytokines, myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide (NO), and tissue levels of Nrf2, HO-1, and NF-kB were evaluated. Compared with untreated UC, all treatment groups showed attenuation of disease-associated changes. The half-dose combination was associated with the lowest cumulative DAI and day-10 DAI, markedly reduced leukocyte infiltration, and lower MPO and inflammatory cytokine levels than either monotherapy in several comparisons. It also normalized MDA and brought NF-kB levels toward those observed in healthy controls, while increasing Nrf2 and HO-1 levels. These findings indicate that low-dose atorvastatin combined with reduced-dose prednisolone can attenuate experimental colonic injury and inflammation more strongly than either monotherapy under the conditions tested.