RESUMO
Abstract Purpose To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, able to modulate the histological changes caused by the NASID (meloxicam). Methods Wistar rats were assigned into three groups (n=6 rats/group): Sham group (saline solution), NSAID group (meloxicam - 15 mg/kg) and Rut-bpy group (100 mg/kg of Rut-bpy associated with 15mg/kg of meloxicam). At the end of experiments, kidneys were removed for histological study, fractal dimension and lacunarity in all animals. Results At the histological examination, all animals (six animals - 100 %) in the NSAID group had membrane thickening and other changes (necrosis, acute tubular congestion and vascular congestion); on the other hand, only one animal (16.6 %) of the Rut-bpy group had congestion. The fractal dimension and lacunarity were greater in the control and Rut-bpy group than in NSAIDs group (p<0.05). Conclusion Rut-bpy may prevent renal histological changes in rats caused by meloxicam.
Assuntos
Animais , Masculino , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Doadores de Óxido Nítrico/farmacologia , Meloxicam/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Distribuição Aleatória , Reprodutibilidade dos Testes , Ratos Wistar , Fractais , Nefropatias/patologiaRESUMO
This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.
Assuntos
Animais , Humanos , Antimaláricos/farmacologia , Complexos de Coordenação/síntese química , Compostos Ferrosos/farmacologia , Compostos Organometálicos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Rutênio/farmacologia , Antimaláricos/síntese química , Linhagem Celular , Cromatografia em Camada Fina , Complexos de Coordenação/farmacologia , Citotoxinas/farmacologia , Compostos Ferrosos/síntese química , Haplorrinos , /parasitologia , Técnicas In Vitro , Compostos Organometálicos/síntese química , Rutênio/química , Tamoxifeno/químicaRESUMO
PURPOSE: To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor in Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6), named according to the treatment applied (G1-Saline, G2-Rut-bpy, G3-L-NAME and G4-L-NAME+Rut-bpy). L-NAME (30 mg/Kg) was injected intraperitoneally 30 minutes before the administration of Rut-bpy (100 mg/Kg). Mean abdominal aorta arterial blood pressure (MAP) was continuously monitored. RESULTS: Mean arterial blood pressure (MAP) in G3 rats rose progressively, reaching 147±16 mmHg compared with 100±19 mm Hg in G1 rats (p<0.05). In G4 rats, treated with L-NAME+Rut-bpy, MAP reached 149+11 mm Hg while in G2 rats, treated with Rut-bpy, MAP values were 106±11 mm Hg. In G1 rats these values decreased progressively reaching 87+14 mm Hg after 30 minutes. An important finding was the maintenance of the MAP throughout the experiment in G2 rats. CONCLUSION: Rut-bpy does not decrease the MAP in L-Name induced hypertensive rats. However, when it is used in anesthetized hypotensive rats a stable blood pressure is obtained.
OBJETIVO: Avaliar o efeitos do Rut-bpy (Cis-[Ru (bpy)2(SO3)(NO)] PF6), um novo doador de óxido nítrico, em ratos hipertensos induzidos pelo éster metílico de N-nitro-L-arginina (L-NAME). MÉTODOS: Vinte e quatro ratos Wistar machos foram distribuídos aleatoriamente em quatro grupos (n = 6), nomeados de acordo com o tratamento aplicado (G1-Salina, G2-Rut-bpy, G3-L-NAME e G4-L-NAME+Rut -bpy). L-NAME (30 mg / Kg) foi injetado por via intraperitoneal 30 minutos antes da administração de Rut-bpy (100 mg / kg). A pressão arterial média (PAM) da aorta abdominal foi monitorada continuamente. RESULTADOS: A pressão arterial média (PAM) em ratos do grupo G3 subiu progressivamente, chegando a 147 ±16 mm Hg, em comparação com 100 ±19 mm Hg em ratos do G1 (p <0,05). Em ratos G4, tratados com L-NAME + Rut-bpy, a PAM atingiu 149±11 milímetros de Hg, enquanto no G2 (ratos tratados com Rut bpy) os valores da PAM foram 106 ±11 mm Hg. No G1 esses valores decresceram progressivamente, atingindo 87±14 mm Hg após 30 minutos. Um achado importante foi a manutenção da PAM durante todo o experimento em ratos do grupo G2. CONCLUSÃO: O uso de Rut bpy não diminui a PAM em ratos hipertensos por L-NAME. No entanto, quando ele é usado em ratos anestesiados, hipotensos, uma pressão arterial estável é obtida.
Assuntos
Animais , Masculino , Ratos , Pressão Sanguínea/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Hipertensão/tratamento farmacológico , Doadores de Óxido Nítrico/farmacologia , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Vasodilatadores/farmacologia , Anestesia , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/biossíntese , Compostos Organometálicos/metabolismo , Distribuição Aleatória , Ratos Wistar , Rutênio/metabolismo , Resultado do Tratamento , Vasodilatadores/metabolismoRESUMO
Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.