Mitigation of chronic glucotoxicity-mediated skeletal muscle atrophy by arachidonic acid.

Toxicity caused by chronic hyperglycemia is a significant factor affecting skeletal muscle myogenesis, resulting in diabetic myopathy. Chronic and persistent hyperglycemia causes activation of the atrophy-related pathways in the skeletal muscles, which eventually results in inflammation and muscle degeneration. To counteract this process, various bioactive compound has been studied for their reversal or hypertrophic effect. In this study, we explored the molecular mechanisms associated with reversing glucotoxicity's effect in C2C12 cells by arachidonic acid (AA). We found a substantial increase in the pro-inflammatory cytokines and ROS production in hyperglycemic conditions, mitigated by AA supplementation. We found that AA supplementation restored protein synthesis that was downregulated under glucotoxicity conditions. AA enhanced myogenesis by suppressing high glucose induced inflammation and ROS production and enhancing protein synthesis. These results imply that AA has cytoprotective actions against hyperglycemia-induced cytotoxicity.

Arachidonic acid modulates the cellular energetics of human pluripotent stem cells and protects the embryoid bodies from embryotoxicity effects in vitro.

Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory effect on mesenchymal stem cells and the vasculogenesis of embryonic stem cells. 3D embryoid bodies (EBs) from pluripotent stem cells (PSCs) have been used as in vitro models for embryotoxicity for various compounds/drugs. Valproic acid (VA), a common anti-epileptic drug, is known to be embryotoxic and cause malformations in embryos. As early embryogenesis depends on AA, we investigated the embryo protective effects of AA against the embryotoxic drug VA in this study. The effects of AA on the proliferation and cell cycle parameters of PSCs were studied. In particular, the potential of AA to abrogate VA-induced embryotoxicity in vitro was evaluated using ROS detection and antioxidant assays. In response to AA, we observed modulation in cell proliferation of induced pluripotent stem cells (iPSCs) and pluripotent NTERA-2 embryonal carcinoma (EC) cells. The present study substantiates the cytoprotective effects of AA against VA. These results imply that AA plays a critical role in the proliferation and differentiation of iPSCs and EC cells and protects the EBs from cytotoxic damage, thereby ensuring normal embryogenesis. Thus, the bioactive lipid AA may be explored for supplementation to benefit pregnant women treated with long-term anti-epileptic drugs to prevent in-utero fetal growth malformations.

Assessment of Mineral Pathophysiology in Patients with Diabetic Foot Ulcer.

Chronic non-healing diabetic foot ulcers (DFU) with a recurrence rate of over 50% in 3 years account for more than 1,08000 non-traumatic lower extremity amputations. Reports of altered mineral status and their role in pathogenesis of diabetes are well documented. However, little is known regarding their status and impact on severity of complications like foot ulcer. A hospital-based case control study was conducted in 64 subjects aged 40-60 years, attending the Podiatric and the Diabetes clinic of the institutional hospitals. Study subjects included were 32 diagnosed cases of type 2 diabetes having foot ulcers along with 32 age-matched diabetics without foot ulcer as controls. Fasting and post-prandial plasma glucose were estimated by glucose oxidase peroxidase method and HbA1c by high-performance liquid chromatography method. Serum zinc, magnesium and copper levels were estimated by colorimetric methods in semi-autoanalyser. Serum levels of zinc, copper and magnesium were significantly decreased in DFU cases as compared with diabetics without ulcers (p < 0.05). Correlation analysis revealed a significant inverse correlation of these minerals with all the glycaemic indices; the association being the strongest in case of zinc in both groups. The higher degree of mineral insufficiencies in the foot ulcer group of this study could be responsible for worsening the glycaemic control in diabetics leading to delayed healing of foot ulcers. The observed decrease of serum copper, magnesium and zinc levels in diabetics with foot ulcers appears to be proportionally related to the length of the diabetic disease. Thus, continuous monitoring and dietary supplementation of minerals in case of severe deficiencies might be beneficial in halting the progression of such complications.