RESUMO
The lack of therapeutics along with complex pathophysiology made non-alcoholic fatty liver disease (NAFLD) a research hotspot. Studies showed that the deficiency of Vitamin D plays a vital role in NAFLD pathogenesis. While several research studies focused on vitamin D supplementation in NAFLD, there is still a need to understand the regulatory mechanism of direct vitamin D receptor activation in NAFLD. In the present study, we explored the role of direct Vitamin D receptor activation using paricalcitol in choline-deficient high-fat diet-induced NAFLD rat liver and its modulation on protein acetylation. Our results showed that paricalcitol administration significantly reduced the fat accumulation in HepG2 cells and the liver of NAFLD rats. Paricalcitol attenuated the elevated serum level of alanine transaminase, aspartate transaminase, insulin, low-density lipoprotein, triglyceride, and increased high-density lipoprotein in NAFLD rats. Paricalcitol significantly decreased the increased total protein acetylation by enhancing the SIRT1 and SIRT3 expression in NAFLD liver. Further, the study revealed that paricalcitol reduced the acetylation of NFκB and FOXO3a in NAFLD liver along with a decrease in the mRNA expression of IL1ß, NFκB, TNFα, and increased catalase and MnSOD. Moreover, total antioxidant activity, glutathione, and catalase were also elevated, whereas lipid peroxidation, myeloperoxidase, and reactive oxygen species levels were significantly decreased in the liver of NAFLD after paricalcitol administration. The study concludes that the downregulation of SIRT1 and SIRT3 in NAFLD liver was associated with an increased acetylated NFκB and FOXO3a. Paricalcitol effectively reversed hepatic inflammation and oxidative stress in NAFLD rats through transcriptional regulation of NFκB and FOXO3a, respectively, by inhibiting their acetylation.
Assuntos
Ergocalciferóis , Proteína Forkhead Box O3 , Fígado , NF-kappa B , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , NF-kappa B/metabolismo , Acetilação/efeitos dos fármacos , Ergocalciferóis/farmacologia , Ergocalciferóis/uso terapêutico , Humanos , Masculino , Ratos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Células Hep G2 , Inflamação/metabolismo , Sirtuína 1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ratos Sprague-Dawley , SirtuínasRESUMO
Delayed wound healing is often caused by bacterial infections and persistent inflammation. Multifunctional materials with anti-bacterial, anti-inflammatory, and hemostatic properties are crucial for accelerated wound healing. In this study, we report a biomacromolecule-based scaffold (ArCh) by uniquely combining arabinogalactan (Ar) and chitosan (Ch) using a Schiff-based reaction. Further, the optimized ArCh scaffolds were loaded with Glycyrrhizin (GA: anti-inflammatory molecule) conjugated NIR light-absorbing Copper sulfide (CuS) nanoparticles. The resultant GACuS ArCh scaffolds were characterized for different wound healing parameters in in-vitro and in-vivo models. Our results indicated that GACuS ArCh scaffolds showed excellent swelling, biodegradation, and biocompatibility in vitro. Further results obtained indicated that GACuS ArCh scaffolds demonstrated mild hyperthermia and enhanced hemostatic, anti-oxidant, anti-bacterial, and wound-healing effects when exposed to NIR light. The scaffolds, upon further validation, may be beneficial in accelerating wound healing and tissue regeneration response.