Exploring the Therapeutic Potential of Ectoine in Duchenne Muscular Dystrophy: Comparison with Taurine, a Supplement with Known Beneficial Effects in the mdx Mouse

Abstract

Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mdx mouse model for DMD but interfered with murine development. In this study, ectoine is evaluated as an alternative for taurine in vitro in CCL-136 cells and in vivo in the mdx mouse. Pre-treating CCL-136 cells with 0.1 mM taurine and 0.1 mM ectoine prior to exposure with 300 U/mL IFN-γ and 20 ng/mL IL-1β partially attenuated cell death, whilst 100 mM taurine reduced MHC-I protein levels. In vivo, histopathological features of the tibialis anterior in mdx mice were mitigated by ectoine, but not by taurine. Osmolyte treatment significantly reduced mRNA levels of inflammatory disease biomarkers, respectively, CCL2 and SPP1 in ectoine-treated mdx mice, and CCL2, HSPA1A, TNF-α and IL-1β in taurine-treated mdx mice. Functional performance was not improved by osmolyte treatment. Furthermore, ectoine-treated mdx mice exhibited reduced body weight. Our results confirmed beneficial effects of taurine in mdx mice and, for the first time, demonstrated similar and differential effects of ectoine.

Ectoine Globally Hypomethylates DNA in Skin Cells and Suppresses Cancer Proliferation

“…To study the possibility of ectoineinduced tumors in HaCaT keratinocytes, we treated cells with ectoine for 30 weeks and xenografted them into athymic nude mice. This experiment was modified from the previous studies [69,70]. Approximately 5 × 10 6 HaCaT cells treated with ectoine for 24 weeks were subcutaneously injected into the dorsal flank of athymic nude mice.…”

Ectoine Globally Hypomethylates DNA in Skin Cells and Suppresses Cancer Proliferation

“…To study the possibility of ectoine-induced tumors in HaCaT keratinocytes, we treated cells with ectoine for 30 weeks and xenografted them into athymic nude mice. This experiment was modified from the previous studies [38,39]. Approximately 5 × 106 HaCaT cells treated with ectoine for 24 weeks were subcutaneously injected into the dorsal flank of athymic nude mice.…”

Changes to the Autophagy-Related Muscle Proteome Following Short-Term Treatment with Ectoine in the Duchenne Muscular Dystrophy Mouse Model MDX

“…In this respect, the use of taurine has been most widely studied and beneficial effects have been observed in mouse models, however, interference with murine development has also surfaced [23], warranting the exploration of alternative compounds. In an earlier study we were the first to study ectoine in the MDX and reported improved skeletal muscle histopathology and anti-inflammatory effects [24]. Ectoine is a natural compound found in extremophiles [25].…”