Phenylbutazone

Myotonic dystrophy type 1 (DM1), caused by expanded CTG repeats that sequester the splicing regulator MBNL1, was the focus of this preclinical investigation. In DM1 model mice, phenylbutazone (PBZ) boosted MBNL1 expression by reducing methylation of an enhancer region in the Mbnl1 gene. PBZ also directly weakened MBNL1 binding to expanded CUG repeats, diminishing nuclear foci formation. Treatment corrected aberrant splicing of Clcn1, Nfix, and Rpn2, restored chloride channel expression, reduced central nuclei in muscle fibers, and improved wheel‑running activity. The authors conclude that PBZ increases functional MBNL1 availability through dual mechanisms, offering a potential DM1 therapy.

Fig. 1 PBZ upregulates MBNL1 expression in C2C12 myoblasts and myotubes. (Chen G, et al., 2016)

In a blinded randomized study, 30 healthy horses received phenylbutazone (a NSAID) with or without a nutritional therapeutic to assess gastrointestinal injury. Phenylbutazone increased gastric ulceration scores by a mean of 1.1 grade and raised circulating bacterial 16S rDNA 3.02‑fold, indicating impaired intestinal barrier function. It also caused specific fecal microbiota changes, including loss of Pseudobutyrivibrio. Co‑administration of the nutritional therapeutic attenuated these detrimental effects. The authors conclude that phenylbutazone causes significant GI injury and barrier dysfunction, which can be partially ameliorated by concurrent nutritional intervention.

Fig. 2 Principal coordinate analysis plots based on the unweighted UniFrac distance measure for each sample within each treatment group as indicated. (Whitfield-Cargile CM, et al., 2021)