RÉSUMÉ
Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of Ghrh and Sst in the hypothalamus does not change, except for Npy and Agrp, while at the pituitary level the Gh, Ghrhr and Ghr genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated Ghr and Igf1r expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.
Sujet(s)
Encéphalomyélite auto-immune expérimentale , Hormone de croissance , Facteur de croissance IGF-I , Animaux , Encéphalomyélite auto-immune expérimentale/métabolisme , Encéphalomyélite auto-immune expérimentale/anatomopathologie , Encéphalomyélite auto-immune expérimentale/génétique , Femelle , Rats , Hormone de croissance/métabolisme , Facteur de croissance IGF-I/métabolisme , Facteur de croissance IGF-I/génétique , Hypothalamus/métabolisme , Hypothalamus/anatomopathologie , Hypophyse/métabolisme , Hypophyse/anatomopathologie , Récepteur STH/métabolisme , Récepteur STH/génétique , Récepteur hormones hypothalamiques hypophysotropes régulatrices/génétique , Récepteur hormones hypothalamiques hypophysotropes régulatrices/métabolisme , Sclérose en plaques/métabolisme , Sclérose en plaques/anatomopathologie , Sclérose en plaques/génétique , Hormone de libération de l'hormone de croissance/métabolisme , Hormone de libération de l'hormone de croissance/génétique , Foie/métabolisme , Foie/anatomopathologie , Modèles animaux de maladie humaineRÉSUMÉ
This study aimed to assess the antioxidant capacity of lemon flavonoid extract Eriomin® (LE) and its impact on cholesterol metabolism in the context of healthy aging. We orally treated 24-month-old male Wistar rats with an LE (40 mg/kg) suspended in 0.3 mL of sunflower oil. At the same time, control groups received an equal volume of sunflower oil (CON) or remained untreated (ICON) daily for 4 weeks. We examined LE's effects on superoxide dismutase and catalase- and glutathione-related enzyme activities, the concentration of lipid peroxides and protein carbonyls, total oxidant status (TOS) and antioxidant status (TAS), and oxidative stress index (OSI) in the liver, jejunum, and ileum. We also measured total cholesterol, its biosynthetic precursors (lanosterol, lathosterol, desmosterol), its degradation products (bile acid precursors) in the serum, liver, jejunum, and ileum, and serum phytosterols (intestinal absorption markers). LE reduced TOS, TAS, and OSI (p < 0.05) compared with control values, indicating its consistent antioxidant action in all examined organs. LE lowered hepatic desmosterol (p < 0.05) while also reducing 7α- and 24-hydroxycholesterol levels in the liver and ileum (p < 0.01). Serum cholesterol, hepatic gene expression, and the immunostaining intensity of CYP7A1 were unchanged. In conclusion, LE exerted non-enzymatic antioxidant effects and reduced cholesterol degradation, reducing its biosynthesis products, thereby maintaining serum cholesterol levels.