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 severe side effects that depend on the dosage. This makes it necessary to find new ways to reduce steroid use. This study looked at how well a combination of half-doses of Atorvastatin and Prednisolone worked in rats with acetic acid-induced colitis. Male Wistar rats were divided into several groups: a normal control group, an untreated UC group, groups receiving full doses of either Atorvastatin (10 mg/kg) or Prednisolone (10 mg/kg), and a group receiving the half-dose combination therapy. After 10 days of oral treatment, researchers analyzed the severity of the disease, colon swelling, tissue damage, pro-inflammatory cytokines, markers of oxidative/nitrosative stress, and related signaling pathways. The half-dose combination treatment was significantly more effective than either full-dose monotherapy. It resulted in the lowest disease severity and almost completely prevented immune cell infiltration in the colon lining. Biochemically, the combination worked together to suppress the NF-κB signaling pathway. This completely normalized levels of tumor necrosis factor-alpha (TNF-α), malondialdehyde (a marker of lipid damage), and NF-κB to healthy levels. It also greatly reduced interleukin-1-beta (IL-1β), interleukin-6 (IL-6), myeloperoxidase activity, and nitric oxide production. Additionally, this combined approach maximized the activity of the protective Nrf2/HO-1 antioxidant pathway more than either monotherapy alone. These results show that combining low-dose Atorvastatin with reduced-dose Prednisolone provides superior anti-inflammatory, immune-modulating, and antioxidant effects through complementary mechanisms. Ultimately, this steroid-sparing treatment offers a very effective strategy to promote mucosal healing in UC while minimizing the severe risks associated with high-dose corticosteroid management.