Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

Abstract

Lipoic acid (LA) and N-acetylcysteine (NAC) are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC). This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS) (2% w/v). LA and/or NAC (100 mg·kg·day−1, each) were given, once a day, in the diet, in a pretreatment phase (7 days) and during UC induction (5 days). Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®). A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2), malondialdehyde (MDA) levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage.

Effects of alpha lipoic acid and its derivative “andrographolid‐lipoic acid‐1” on ulcerative colitis: A systematic review with meta‐analysis of animal studies

“…Three out of 10 studies have assessed the TNF-α level following ALA administration compared with the controls in rats. Moura et al 54 indicated that ALA reduced colonic TNF-α level insignificantly. Similarly, Sehirli et al 51 reported that ALA caused a notable decline in TNF-α expression in colitis rats.…”

“…47 showed that ALA (different doses) significantly reduced the TNF-α content in tissue or the plasma during the treatment course and afterward when compared with the control group. 50,51,54 El-Goweli et al 50 found that ALAtreated group with a potency similar to cyclosporine (CSA) and their combination decreased the TNF-α level significantly when compared with the control. Three out of 10 studies have assessed the TNF-α level following ALA administration compared with the controls in rats.…”

“…51 treatment, the MPO content was insignificantly decreased when compared with the control animals. 54 Yang et al 55 demonstrated that AL-1 at all concentration tested, considerably suppressed the MPO activity compared with the control mice (Table 3). 54 Yang et al 55 demonstrated that AL-1 at all concentration tested, considerably suppressed the MPO activity compared with the control mice (Table 3).…”

“…46 According to Sun et al, 46 ALA significantly inhibited the increase of MDA compared with placebo ( Table 1). 50 Moura et al 54 (2016) illustrated that ALA alone or in combination with F I G U R E 4 Individual and pooled effect size for the outcome of "ΔMPO" in the studies considering ALA compared with placebo therapy in UC in 32 rats. 50-54 Sehirli et al 51 and Kolgazi et al 53 showed that ALA treatment significantly lessened the MDA level in rat UC model, where administered orally or intraperitoneally compared with the control.…”

Evaluation of the Potential Antioxidant Role of High-Density Lipoprotein-Cholesterol (HDL-C) in Patients with Ulcerative Colitis

“…In addition, use of antioxidants is an important complementary treatment in cardiometabolic, neurological, and gastrointestinal disorders (29), such as ulcerative colitis. The findings of the present study demonstrated that the serum HDL-C level decreased in patients with ulcerative colitis in comparison to the healthy controls.…”