ABSTRACT
Palmitoylethanolamide (PEA) regulates many pathophysiological processes in the central nervous system, including pain perception, convulsions and neurotoxicity, and increasing evidence points to its neuroprotective action. In the present study, we report that PEA, acting as a ligand of peroxisome-proliferator activated receptor (PPAR)-α, might regulate neurosteroidogenesis in astrocytes, which, similar to other glial cells and neurones, have the enzymatic machinery for neurosteroid de novo synthesis. Accordingly, we used the C6 glioma cell line and primary murine astrocytes. In the mitochondrial fraction from cells stimulated with PEA, we demonstrated an increase in steroidogenic acute regulatory protein (StAR) and cytochrome P450 enzyme (P450scc) expression, both comprising proteins considered to be involved in crucial steps of neurosteroid formation. The effects of PEA were completely blunted by GW6471, a selective PPAR-α antagonist, or by PPAR-α silencing by RNA interference. Accordingly, allopregnanolone (ALLO) levels were increased in supernatant of PEA-treated astrocytes, as revealed by gas chromatography-mass spectrometry, and this effect was inhibited by GW6471. Moreover, PEA showed a protective effect, reducing malondialdehyde formation in cells treated with l-buthionine-(S,R)-sulfoximine, a glutathione depletor and, interestingly, the effect of PEA was partially inhibited by finasteride, a 5α-reductase inhibitor. A similar profile of activity was demonstrated by ALLO and the lack of an additive effect with PEA suggests that the reduction of oxidative stress by PEA is mediated through ALLO synthesis. The present study provides evidence indicating the involvement of the saturated acylethanolamide PEA in ALLO synthesis through PPAR-α in astrocytes and explores the antioxidative activity of this molecule, confirming its homeostatic and protective role both under physiological and pathological conditions.
Subject(s)
Astrocytes/metabolism , Brain Neoplasms/metabolism , Glioma/metabolism , PPAR alpha/physiology , Palmitic Acids/pharmacology , Pregnanolone/biosynthesis , Amides , Animals , Animals, Newborn , Astrocytes/cytology , Astrocytes/drug effects , Brain Neoplasms/pathology , Cell Culture Techniques , Cell Line, Tumor , Cells, Cultured , Drug Evaluation, Preclinical , Endocannabinoids , Ethanolamines , Glioma/pathology , Mice , Mice, Inbred BALB C , PPAR alpha/genetics , PPAR alpha/metabolism , Rats , Up-Regulation/drug effectsSubject(s)
Neuroimmunomodulation/physiology , Prolactin/physiology , Adult , Animals , Brain/metabolism , Carrageenan/toxicity , Edema/chemically induced , Edema/physiopathology , Humans , Hyperprolactinemia/physiopathology , Hypothalamus/metabolism , Infant, Newborn , Inflammation/physiopathology , Kidney , Lymphocytes/metabolism , Pituitary Gland/transplantation , Pleurisy/chemically induced , Pleurisy/physiopathology , Prolactin/metabolism , Rabbits , Rats , Receptors, Prolactin/metabolism , Receptors, Prolactin/physiology , Transplantation, HeterotopicABSTRACT
The laxative effect of senna has been investigated in normal and essential fatty acid deficient (EFAD) rats. Oral administration of senna pod extract (7-5-90 mg kg-1) produced a dose-dependent increase in the number of soft faeces excreted by normal rats. Senna 30 mg kg-1 also reversed net absorption of water and increased the prostaglandin (PG) production in the colonic lumen of normal rats by about four times. Oral administration of senna pod extract to rats, maintained on a fat-free diet for 30-90 days, produced diarrhoea and reversed net absorption of water as in normal rats. However, a fat-free diet reduced the PG production drastically in the colonic lumen both in senna-free rats and in senna-treated rats. In EFAD rats carrageenan oedema, but not dextran oedema, was also drastically reduced. Since PG mediation is not present in EFAD rats we conclude that the PG are not essential for laxation induced by senna and that water secretion and PG production in the rat intestinal lumen are unrelated.
Subject(s)
Cathartics , Fatty Acids, Essential/deficiency , Senna Extract/pharmacology , Animals , Body Water/metabolism , Diet , Edema/physiopathology , Feces , Male , Prostaglandins/biosynthesis , Rats , Rats, Inbred Strains , Time FactorsABSTRACT
Fungi of six families, encompassing 28 species, have been screened for their inhibitory effects on adenosine-5'-diphosphate (ADP), acetyl-glyceryl-phosphorylcholine (PAF) or collagen-induced rabbit platelet aggregation. Some fungi have also been studied for their ability to inhibit neutrophil aggregation induced by calcium ionophore A 23187. The results suggest that fungi may be a potential source of inhibitors of platelet and neutrophil aggregation.
Subject(s)
Fungi/metabolism , Neutrophils/drug effects , Platelet Aggregation/drug effects , Adenosine Diphosphate/pharmacology , Animals , Calcimycin/pharmacology , Cell Aggregation/drug effects , Collagen/pharmacology , Dialysis , Freeze Drying , Fungi/analysis , In Vitro Techniques , Male , RabbitsABSTRACT
The laxation induced by senna is not modified in rats either maintained on a diet deficient in essential fatty acids (EFAD) or exposed to cold (6 degrees C) or with yeast-induced fever. In light of our findings it appears conceivable that non-PG-mediated mechanism(s) play a relevant role in laxation induced by senna.