Therapeutic potentials of vitamin C, zinc, and selenium in DSS-induced colitis in mice: Zinc combination exhibits superior synergistic effects

Standard treatments of inflammatory bowel diseases frequently demonstrate limited long-term efficacy and are associated with significant side effects, necessitating the exploration of safer therapeutic alternatives. This study aimed to compare the therapeutic efficacy of vitamin C (VitC) administered alone or in combination with either zinc (Zn) or selenium (Se) in a murine dextran sodium sulfate (DSS)-induced colitis model. Sixty male BALB/c mice were randomly allocated into five groups (n = 12): Control, DSS, and three DSS-treated groups receiving VitC monotherapy (100 mg/kg), VitC plus Zn (100 mg/kg + 30 mg/kg), or VitC plus Se (100 mg/kg + 0.5 mg/kg). Treatments were administered daily from day 19 to 28 post-DSS exposure. Body weight, temperature, serum TNF-α and IgG2a levels, and colonic histopathology were assessed. DSS-induced weight loss, hypothermia, cytokine elevation, and colonic damage were significantly reduced in all treatment groups compared with DSS-only controls (p < 0.05). By day 28, the VitC plus Se group achieved the highest body weight (22.8 ± 0.3 g), followed by VitC plus Zn (22.0 ± 0.5 g). However, the VitC plus Zn combination demonstrated superior efficacy in temperature stabilization, TNF-α suppression, and histological preservation of mucosal integrity compared to both monotherapy and the Se combination. These findings indicate that VitC combined with Zn exhibits potent anti-inflammatory and tissue-protective effects mediated primarily through immunomodulatory mechanisms rather than nutritional restoration. Furthermore, Zn-containing micronutrient formulations may represent promising adjunctive strategies for managing inflammatory bowel disease, warranting further translational investigation.