ABSTRACT
Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds.
Plataformas capazes de armazenar, liberar ou capturar NO de forma controlada e específica são de grande interesse tendo-se em vista aplicações biológicas. Dentre as possíveis matrizes que podem ser utilizadas para esse fim, os dendrímeros são excelentes candidatos. Essas moléculas têm sido empregadas em sistemas para o transporte de fármacos e apresentam propriedades interessantes tais como a possibilidade de modificações químicas em sua superfície, a capacidade de estocar altas concentrações de compostos de interesse em uma só molécula e a possibilidade de aumentar a solubilidade e a biocompatibilidade dos compostos a eles ligados. Esta revisão enfatiza os recentes avanços no desenvolvimento e nas aplicações biológicas de diferentes dendrímeros liberadores de NO e a forma em que o óxido nítrico é liberado nesses compostos.
Subject(s)
Dendrimers/analysis , Nitric Oxide/analysis , Chemistry, PharmaceuticalABSTRACT
BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70 percent) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02). CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.