Papel de produtos finais de glicação avançada nas alterações hepáticas e metabólicas em modelo experimental de síndrome metabólica / Role of advanced glycation end products in liver and metabolic changes in an experimental model of metabolic syndrome

A doença hepática gordurosa não alcoólica (DHGNA) afeta um terço da população adulta e é definida como o acúmulo de gordura no fígado de indivíduos que não consomem excessiva quantidade de álcool. No entanto, os mecanismos moleculares responsáveis pela progressão da doença ainda não foram completamente elucidados. Estudos anteriores do nosso grupo e outros autores demonstraram que o aumento nos níveis de produtos finais de glicação avançada (AGEs) e distúrbios da microcirculação estão presentes na DHGNA, mas nenhuma evidência direta da ligação entre os níveis de AGEs, estresse oxidativo, inflamação e alterações microcirculatórias hepáticas foi demonstrada. No presente trabalho, nós investigamos os efeitos protetores da piridoxamina (PirPM), um inibidor da formação de AGEs, nas complicações metabólicas e microcirculatórias na DHGNA. A DHGNA foi induzida por uma dieta hiperlipídica (HFD) em ratos Wistar durante 28 semanas. O tratamento com Pir (60 mg/Kg/dia, i.p.) foi administrado entre as semanas 20 e 28. Na microcirculação do fígado, o recrutamento de leucócitos e o número de células estreladas hepáticas (HSC´s) ativadas foram examinados por microscopia intravital.

A perfusão tecidual foi acessada por fluxometria utilizando o laser speckle. O estresse oxidativo e o marcador de inflamação foram avaliados pela dosagem de substâncias reativas ao ácido tiobarbitúrico (TBARs) e RT-PCR, respectivamente. Os AGEs no fígado foram avaliados por espectroscopia de fluorescência. Foi observado que a alteração no metabolismo da glicose e aumento do peso corporal, hepático e de tecido adiposo e esteatose no grupo DHGNA foi revertido pelo tratamento com Pir. Em relação aos parâmetros microcirculatórios hepáticos, ratos com DHGNA apresentaram aumento do rolamento e adesão de leucócitos, da ativação de HSCs e diminuição da perfusão tecidual. A Pir mostrou um efeito vasoprotetor nas alterações da microcirculação hepática induzidas pela DHGNA. O fígado de grupo DHGNA apresentou níveis elevados de peroxidação lipídica, que foram parcialmente revertidos pelo tratamento com Pir. Em conclusão, a Pir apresenta importante efeito vasoprotetor e antioxidante, além de modular os distúrbios metabólicos, sendo, portanto, um potencial tratamento para complicações microcirculatórias e metabólicas associadas à DHGNA. (AU)

Effect of telmisartan and pyridoxamine on oxidative stress in brain tissue of spontaneously hypertensive rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effect of telmisartan and pyridoxamine on oxidative stress in brain tissue of spontaneously hypertensive rats.</p><p><b>METHODS</b>Twenty-four spontaneously hypertensive rats were randomly divided into four groups (n = 6): hypertensive control group (HC group), telmisartan group (T group ), pyridoxamine group (P group ), telmisartan and pyridoxamine group (TP group). Wistar-Kyoto (WKY) rats of the same age were served as a normal control group (NC group). Drug treatment lasted for 16 weeks the level of hyde (MDA) in rat brain tissue, as well as superoxide dismutase (SOD) activity and nicotinamide adenine dinucleotide phosphate(NADHP) oxidase p47phox mRNA expression were observed in this study.</p><p><b>RESULTS</b>The MDA level in brain in HC group were higher than that in NC group and the SOD activity were lower (P < 0.05). T group, P group and TP group had lower MDA level and higher SOD activity than HC group (P < 0.05). The NADPH mRNA in brain in HC group were significantly higher than that in NC group (P < 0.01). T group and TP group had decreased levels of NADPH mRNA (P < 0.01), there was no significant difference between HC group and P group (P > 0.05).</p><p><b>CONCLUSION</b>The brain tissue of spontaneous hypertensive rats had been under the status of oxidative stress. Single application of either telmisartan or pyridoxamine could inhibit oxidative stress of brain tissue. However, compare with single treatment of telmisartan, no beneficial effects were observed in combined use of telmisartan and pyridoxamine.</p>

Effects of telmisartan and pyridoxamine on abdominal aorta vascular remodeling in spontaneously hypertensive rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of telmisartan and pyridoxamine on vascular smooth muscle cells (VSMCs) proliferation and apoptosis as well as abdominal aorta vascular remodeling in spontaneously hypertensive rats (SHRs).</p><p><b>METHODS</b>SHRs randomly received placebo, telmisartan (6 mg kg(-1) x d(-1)), pyridoxamine (200 mg x kg(-1) x d(-1)) or telmisartan (6 mg x kg(-1) x d(-1)) plus pyridoxamine (200 mg x kg(-1) x d(-1), n = 12 each) for 16 weeks. Wistar-Kyoto (WKY, n = 12) rats serve as normotensive control. The systolic blood pressure (SBP) of rat was measured before and weekly thereafter. The serum advanced glycation end-products (AGEs) were detected by competitive ELISA. The serum super oxide dismutase (SOD) and nitric oxide (NO) were measured. The abdominal aorta were assessed by image analysis in HE stained sections. The VSMCs apoptosis and proliferation in abdominal aorta were detected with in situ end labeling technique and proliferating cell nuclear antigen (PCNA) immunohistochemistry staining respectively.</p><p><b>RESULTS</b>SBP were significantly lower in telmisartan and telmisartan plus pyridoxamine therapy group than in placebo treated hypertensive rats while not affected by pyridoxamine (P > 0.05). Activity of SOD and NO were significantly higher and AGEs significantly lower in telmisartan, pyridoxamine and combination therapy treated SHRs than in placebo treated hypertensive rats (P < 0.01). The telmisartan, pyridoxamine and combination therapy can significantly inhibit the PCNA expression and significantly enhance the apoptosis value in abdominal aorta (P < 0.01). The efficacy of combined treatment was significantly higher than telmisartan and pyridoxamine alone (P < 0.05).</p><p><b>CONCLUSION</b>Telmisartan and pyridoxamine could attenuate abdominal aorta vascular remodeling via reducing oxidative stress and AGEs production as well as restoring the balance of VSMCs proliferation and apoptosis in SHRs abdominal aorta.</p>

Complexes of vitamin B6 ternary complexes of Cu[2] with pyridoxamine and amino acids, DNA units or peptides

Equilibrium-based computer models were used to calculate the stability constants of the ternary complexes of CuII involving pyridoxamine [PM] as well as amino acids, DNA units or peptides, from the results of pH-metric data at 25 degree. It was concluded that PM would be the first compound bound to CuII, followed by ligation of the secondary ligand [amino acids, DNA or peptides]. Mixed ligand complexes of the general formula Cu [PM] L, where L = threonine, uracil and glycyl- glycine, were synthesized and characterized by elemental analysis, molar conductance, magnetic susceptibility, electronic spectra, IR, and X-ray diffraction measurements