Research Paper Volume 17, Issue 3 pp 757—777

Figure 2. ADAM19 inhibition by BB-94 treatment reduces intestinal permeability and inflammation in mice caused by doxorubicin treatment. (A) Experimental design to determine the effect of ADAM19 inhibition in a mouse model. Mice received a single dose, i.p. Dox (10 mg/Kg) or vehicle (SHAM Ctrl) at the start of the experiment. Followed by a subset of mice receiving Batimastat BB-94 doses of 5 mg/Kg and 20 mg/Kg once a week, every other week till week 5. Intestinal permeability and inflammation were measured on week six in the colon of dissected mice. (B) Albumin levels were measured using an ELISA assay in early morning fecal samples from each group. The graph presents albumin levels as mean ± SEM, expressed in mg per 100 mg/ml of fecal material, from (n = 6) across. Significant differences in albumin levels between groups (e.g., Sham vs. doxo, doxo vs. BB-94 treated mice at 5 mg/kg and 20 mg/kg, etc.) were assessed using ANOVA, with p-values indicated as ^*p < 0.05, ^**p < 0.01, ^***p < 0.001. Elevated albumin levels in feces may indicate increased intestinal permeability or gut damage, reflecting potential gastrointestinal dysfunction in doxo-treated mice, while treatment with BB-94 significantly reduced it. (C) qRT-PCR was performed with RNA prepared from dissected colon tissue of mice treated as described above. The results are presented as mean relative fold change in the gene expression of IL-6 and normalized to the housekeeping gene Actin. (D) Mean relative fold change in the gene expression of p21 and normalized to the housekeeping gene Actin. (B–D) Error bars indicate SEM. The significance level was determined by ANOVA and denoted by asterisks: ^*p < 0.05, ^**p < 0.01, ^***p < 0.001, and ^****p < 0.0001.