Epoxyeicosatrienoic acids (EETs) and their synthetic analogs have cardiovascular protective effects. Here, we investigated the action of a novel EET analog EET-B on the progression of post-myocardial infarction (MI) heart failure in spontaneously hypertensive rats (SHR). Adult male SHR were divided into vehicle- and EET-B (10 mg/kg/day; p.o., 9 weeks)-treated groups. After 2 weeks of treatment, rats were subjected to 30-min left coronary artery occlusion or sham operation. Systolic blood pressure (SBP) and echocardiography (ECHO) measurements were performed at the beginning of study, 4 days before, and 7 weeks after MI. At the end of the study, tissue samples were collected for histological and biochemical analyses. We demonstrated that EET-B treatment did not affect blood pressure and cardiac parameters in SHR prior to MI. Fractional shortening (FS) was decreased to 18.4 ± 1.0% in vehicle-treated MI rats compared with corresponding sham (30.6 ± 1.0%) 7 weeks following MI induction. In infarcted SHR hearts, EET-B treatment improved FS (23.7 ± 0.7%), markedly increased heme oxygenase-1 (HO-1) immunopositivity in cardiomyocytes and reduced cardiac inflammation and fibrosis (by 13 and 19%, respectively). In conclusion, these findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce cardiac remodeling in SHR subjected to MI.

• MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• infarkt myokardu farmakoterapie   genetika   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• kyseliny arachidonové aplikace a dávkování   chemie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední SHR MeSH
• srdce patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Brain monoamines are involved in many of the same processes affected by neuropsychiatric disorders and psychotropic drugs, including cannabinoids. This study investigated in vitro effects of cannabinoids on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters and affecting brain development and function. The effects of the phytocannabinoid Delta(9)-tetrahydrocannabinol (THC), the endocannabinoid anandamide (N-arachidonoylethanolamide [AEA]), and the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) on the activity of MAO were measured in a crude mitochondrial fraction isolated from pig brain cortex. Monoamine oxidase activity was inhibited by the cannabinoids; however, higher half maximal inhibitory concentrations (IC(50)) of cannabinoids were required compared to the known MAO inhibitor iproniazid. The IC(50) was 24.7 micromol/l for THC, 751 micromol/l for AEA, and 17.9 micromol/l for WIN when serotonin was used as substrate (MAO-A), and 22.6 micromol/l for THC, 1,668 micromol/l for AEA, and 21.2 micromol/l for WIN when phenylethylamine was used as substrate (MAO-B). The inhibition of MAOs by THC was noncompetitive. N-Arachidonoylethanolamide was a competitive inhibitor of MAO-A and a noncompetitive inhibitor of MAO-B. WIN was a noncompetitive inhibitor of MAO-A and an uncompetitive inhibitor of MAO-B. Monoamine oxidase activity is affected by cannabinoids at relatively high drug concentrations, and this effect is inhibitory. Decrease of MAO activity may play a role in some effects of cannabinoids on serotonergic, noradrenergic, and dopaminergic neurotransmission.

• MeSH
• benzoxaziny aplikace a dávkování   farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• inhibitory MAO aplikace a dávkování   farmakologie   MeSH
• iproniazid aplikace a dávkování   farmakologie   MeSH
• kyseliny arachidonové aplikace a dávkování   farmakologie   MeSH
• monoaminoxidasa účinky léků   metabolismus   MeSH
• morfoliny aplikace a dávkování   farmakologie   MeSH
• mozek účinky léků   enzymologie   MeSH
• naftaleny aplikace a dávkování   farmakologie   MeSH
• polynenasycené alkamidy aplikace a dávkování   farmakologie   MeSH
• prasata MeSH
• tetrahydrokanabinol aplikace a dávkování   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: Dysregulation of the balance between cell growth and death in the colonic epithelium is associated with cancer promotion. Understanding how cell death in this self-renewing tissue is regulated and how it is influenced by interaction of specific dietary components, especially fat and fibre, could lead to improved treatment and prevention strategies for cancer. AIM OF THE STUDY: The effects of two types of polyunsaturated fatty acids (PUFAs)--arachidonic (AA, 20:4, n-6) or docosahexaenoic (DHA, 22:6, n-3)--on the response of human colon adenocarcinoma HT-29 cells to sodium butyrate (NaBt) were investigated. METHODS: The parameters reflecting cell proliferation and cell death were studied together with oxidative response, mitochondrial membrane potential (MMP) and changes of selected regulatory molecules associated with cell cycle (p27(Kip1) and p21(Cip1/WAF1)) and apoptosis (caspase-3, caspase-9, poly (ADP-ribose) polymerase--PARP, Bcl-2, Bax, Bak,Mcl-1). RESULTS: We demonstrated that pre-treatment with either AA or DHA attenuated cell cycle arrest caused by NaBt which is associated with modulation of p27(Kip1), but not p21(Cip1/WAF1) protein expression. On the other hand, PUFAs sensitised HT-29 cells to NaBt-induced apoptosis. An increased amount of floating cells and cells in the subG(0)/G(1) population was associated with increased reactive oxygen species production, lipid peroxidation, decrease of MMP, activation of caspase-3 and -9, PARP cleavage, and decrease in the expression of antiapoptotic Mcl-1 protein. The observed effects were modulated by the addition of a protein synthesis inhibitor, cycloheximide, and partially reversed by the antioxidant Trolox. CONCLUSIONS: PUFAs may have beneficial effects in the colon enhancing apoptosis induced by NaBt. Alteration of cell membrane lipid composition and potentiation of oxidative processes accompanied by changes in mitochondria followed by stimulation of apoptotic cascade components play a role in these effects.

• MeSH
• adenokarcinom * metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• buňky HT-29 MeSH
• butyráty * metabolismus   MeSH
• fluorescenční mikroskopie MeSH
• kaspasa 3 MeSH
• kaspasa 9 MeSH
• kaspasy metabolismus   účinky léků   MeSH
• kyseliny arachidonové aplikace a dávkování   MeSH
• kyseliny dokosahexaenové aplikace a dávkování   MeSH
• lidé MeSH
• membránové potenciály účinky léků   MeSH
• nádory tračníku * metabolismus   MeSH
• nenasycené mastné kyseliny * metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• poly(ADP-ribosa)-polymerasy metabolismus   účinky léků   MeSH
• protoonkogenní proteiny metabolismus   účinky léků   MeSH
• průtoková cytometrie MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH