S-allylmercaptocysteine attenuates posaconazole-induced adverse effects in mice through antioxidation and anti-inflammation

Posaconazole is a broad-spectrum antibacterial drug for the treatment of invasive fungal infections. However, its clinical usage is limited by a lot of adverse reactions such as diarrhea. S-allylmercaptocysteine (SAMC), a garlic organosulfur compound, has a strong antioxidative and anti-inflammatory activity. This study aimed to examine the protective effects of SAMC on posaconazole-induced adverse effects. Mice were treated with the blank control, enteric coated posaconazole microparticles (POS group) and its combination with SAMC (Combination group). Oxidative stress markers, antioxidative activities and histological changes in the study mice were investigated. We found that the percentage of mice diarrhea was reduced by 20% in the combination group after administration for 1 week. The results reveal that the levels of TNF-α (p < 0.05), IL-1β (p < 0.01) and IL-6 (p < 0.01) in the serum of the POS group were significantly higher compared to the control group while the combination group decreased the POS-induced cytokine elevations (p < 0.05). The MDA content in colon tissues of the POS group increased distinctly (p < 0.01) compared with the control group. The combination groups dosed with the low and high strengths of SAMC decreased the MDA level about 20% and 30%, respectively, compared to the POS group. The histopathological results display that the colonic tissues of the combination groups had significant improvement in mucosal adhesions and inflammatory infiltration versus the POS group. Briefly, SAMC could alleviate the POS-induced adverse reactions by the mechanisms of antioxidation and anti-inflammation.