Previous studies of thermal degradation of folic acid have not given consistent rate expressions or activation energies. The present study employed a model system which eliminated oxygen mass transfer limitations to examine degradation as a result of heating. A pseudo first-order reaction rate constant (k ah& and an activation energy (E,) for thermal degradation due to an oxidative mechanism were estimated to be 0.154 f 0.044 min-' and 16.3 kcal/mol, respectively.In the presence of Nz, these parameters were estimated to be 0.094 ? 0.009 min-' and 23.3 kcal/mol, respectively. While elimination of oxygen will not ensure folic acid retention, the overall degradation rate will be reduced significantly.
Background
In this study we investigated the contribution of high-fat diet-induced metabolic overload to osteoarthritis (OA) progression originally caused by mild mechanical trauma to the mouse knee joint. We hypothesized that metabolic stress would induce a proinflammatory environment by altering systemic lipid levels and immune cell populations.
Methods
Twelve-week-old male C57BL/6J mice (n=20) were given a low-fat diet (LFD, 10%kcal from fat) or high-fat diet (HFD, 45%kcal from fat) for 18 weeks. OA was initiated by transecting the medial meniscotibial ligament of the right knee joint at t=10 weeks. OA severity and changes in M1/M2 polarization of synovial macrophage populations were determined in serial coronal FFPE-mounted sections. Eicosanoid levels and monocyte populations were evaluated before and after ligament transection.
Results
Diet-induced metabolic stress assessed by body weight, systemic cholesterol levels, and insulin resistance index was significantly higher in HFD mice. This group also showed increased cartilage damage, synovitis, and osteophyte formation compared with LFD controls. High-fat feeding elevated systemic arachidonic acid levels, which mainly resulted in increased levels of its cytochrome P450-catalysed diol metabolites 5,6-dihydroxyeicosatrienoic acid (DHET) and 8,9-DHET. High-fat feeding also triggered an increase in pro-inflammatory intermediate CD43++Ly6Cint monocytes after ligament resection. Ligament resection in addition to high-fat feeding induced increased expression of the activation marker CD11c selectively on non-classical CD43++Ly6Clow monocytes. No significant changes in synovial macrophage polarization were observed.
Conclusions
Metabolic stress resulted in a proinflammatory environment and aggravated injury-induced OA progression. Our results suggest that a CYP450-focused eicosanoid metabolism and activated circulating monocytes may be drivers of this metabolic stress-induced OA progression, contributing to the mechanistic understanding and potentially serving as future diagnostic and prognostic biomarkers for metabolic OA.
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