FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2010414623> ?p ?o ?g. }

• W2010414623 abstract "Abstract Background Current evidence suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of basal ganglia injury. Reportedly, nonsteroidal anti-inflammatory drugs (NSAIDs) mitigate DAergic neurotoxicity in rodent models of PD. Consistent with these findings, epidemiological analysis indicated that certain NSAIDs may prevent or delay the progression of PD. However, a serious impediment of chronic NSAID therapy, particularly in the elderly, is gastric, renal and cardiac toxicity. Nitric oxide (NO)-donating NSAIDs, have a safer profile while maintaining anti-inflammatory activity of parent compounds. We have investigated the oral activity of the NO-donating derivative of flurbiprofen, [2-fluoro-α-methyl (1,1'-biphenyl)-4-acetic-4-(nitrooxy)butyl ester], HCT1026 (30 mg kg -1 daily in rodent chow) in mice exposed to the parkinsonian neurotoxin MPTP. Methods Ageing mice were fed with a control, flurbiprofen, or HCT1026 diet starting ten days before MPTP administration and continuing for all the experimental period. Striatal high affinity synaptosomial dopamine up-take, motor coordination assessed with the rotarod, tyrosine hydroxylase (TH)- and dopamine transporter (DAT) fiber staining, stereological cell counts, immunoblotting and gene expression analyses were used to assess MPTP-induced nigrostriatal DAergic toxicity and glial activation 1-40 days post-MPTP. Results HCT1026 was well tolerated and did not cause any measurable toxic effect, whereas flurbiprofen fed mice showed severe gastrointestinal side-effects. HCT1026 efficiently counteracted motor impairment and reversed MPTP-induced decreased synaptosomal [ 3 H]dopamine uptake, TH- and DAT-stained fibers in striatum and TH + neuron loss in subtantia nigra pars compacta (SNpc), as opposed to age-matched mice fed with a control diet. These effects were associated to a significant decrease in reactive macrophage antigen-1 (Mac-1)-positive microglial cells within the striatum and ventral midbrain, decreased expression of iNOS, Mac-1 and NADPH oxidase (PHOX), and downregulation of 3-Nitrotyrosine, a peroxynitrite finger print, in SNpc DAergic neurons. Conclusions Oral treatment with HCT1026 has a safe profile and a significant efficacy in counteracting MPTP-induced dopaminergic (DAergic) neurotoxicity, motor impairment and microglia activation in ageing mice. HCT1026 provides a novel promising approach towards the development of effective pharmacological neuroprotective strategies against PD." @default.
• W2010414623 created "2016-06-24" @default.
• W2010414623 creator A5001302471 @default.
• W2010414623 creator A5013252840 @default.
• W2010414623 creator A5020938978 @default.
• W2010414623 creator A5021181399 @default.
• W2010414623 creator A5026727116 @default.
• W2010414623 creator A5031496401 @default.
• W2010414623 creator A5075407827 @default.
• W2010414623 creator A5077892371 @default.
• W2010414623 date "2010-11-23" @default.
• W2010414623 modified "2023-09-30" @default.
• W2010414623 title "Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease" @default.
• W2010414623 cites W1480874656 @default.
• W2010414623 cites W1528904262 @default.
• W2010414623 cites W1530199299 @default.
• W2010414623 cites W1563590122 @default.
• W2010414623 cites W1580441010 @default.
• W2010414623 cites W1775749144 @default.
• W2010414623 cites W1967805987 @default.
• W2010414623 cites W1974924674 @default.
• W2010414623 cites W1975331070 @default.
• W2010414623 cites W1975774284 @default.
• W2010414623 cites W1980541855 @default.
• W2010414623 cites W1983455948 @default.
• W2010414623 cites W1985577234 @default.
• W2010414623 cites W1988424636 @default.
• W2010414623 cites W1989279492 @default.
• W2010414623 cites W1990000696 @default.
• W2010414623 cites W1992911806 @default.
• W2010414623 cites W1993829231 @default.
• W2010414623 cites W1994464747 @default.
• W2010414623 cites W1997781505 @default.
• W2010414623 cites W1999627663 @default.
• W2010414623 cites W2003070284 @default.
• W2010414623 cites W2003473535 @default.
• W2010414623 cites W2005089402 @default.
• W2010414623 cites W2006306666 @default.
• W2010414623 cites W2012557172 @default.
• W2010414623 cites W2013884291 @default.
• W2010414623 cites W2015450850 @default.
• W2010414623 cites W2017364016 @default.
• W2010414623 cites W2020656090 @default.
• W2010414623 cites W2022325044 @default.
• W2010414623 cites W2022911097 @default.
• W2010414623 cites W2028972354 @default.
• W2010414623 cites W2030536065 @default.
• W2010414623 cites W2032067765 @default.
• W2010414623 cites W2033558692 @default.
• W2010414623 cites W2036600670 @default.
• W2010414623 cites W2037847760 @default.
• W2010414623 cites W2038814798 @default.
• W2010414623 cites W2039357975 @default.
• W2010414623 cites W2039519865 @default.
• W2010414623 cites W2040558323 @default.
• W2010414623 cites W2041046421 @default.
• W2010414623 cites W2042630261 @default.
• W2010414623 cites W2043676089 @default.
• W2010414623 cites W2052770514 @default.
• W2010414623 cites W2056546282 @default.
• W2010414623 cites W2059884588 @default.
• W2010414623 cites W2063285691 @default.
• W2010414623 cites W2064127705 @default.
• W2010414623 cites W2064143300 @default.
• W2010414623 cites W2068312274 @default.
• W2010414623 cites W2069849992 @default.
• W2010414623 cites W2073557865 @default.
• W2010414623 cites W2074425861 @default.
• W2010414623 cites W2076403655 @default.
• W2010414623 cites W2077840364 @default.
• W2010414623 cites W2079768378 @default.
• W2010414623 cites W2079856528 @default.
• W2010414623 cites W2082510957 @default.
• W2010414623 cites W2084100208 @default.
• W2010414623 cites W2084506085 @default.
• W2010414623 cites W2085667648 @default.
• W2010414623 cites W2090412410 @default.
• W2010414623 cites W2091267020 @default.
• W2010414623 cites W2093994279 @default.
• W2010414623 cites W2095149099 @default.
• W2010414623 cites W2095376584 @default.
• W2010414623 cites W2098097762 @default.
• W2010414623 cites W2100042702 @default.
• W2010414623 cites W2103597137 @default.
• W2010414623 cites W2103738800 @default.
• W2010414623 cites W2109759840 @default.
• W2010414623 cites W2110902451 @default.
• W2010414623 cites W2111464898 @default.
• W2010414623 cites W2114049362 @default.
• W2010414623 cites W2116819366 @default.
• W2010414623 cites W2120331429 @default.
• W2010414623 cites W2120412340 @default.
• W2010414623 cites W2128631317 @default.
• W2010414623 cites W2131884118 @default.
• W2010414623 cites W2136004258 @default.
• W2010414623 cites W2143500251 @default.
• W2010414623 cites W2144078756 @default.
• W2010414623 cites W2145903555 @default.
• W2010414623 cites W2146008698 @default.
• W2010414623 cites W2147830608 @default.

• next