Ambiguous effect of dendrimer PAMAM G3 on rat heart respiration in a model of an experimental diabetes - Objective causes of laboratory misfortune or unpredictable G3 activity?

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• 作者：Karolina Siewiera^a ; ¹ ; ^{ksiewiera@gmail.com} ; Magdalena Labieniec-Watala^b ; ¹ ; ^{magdalab@biol.uni.lodz.pl}
• 关键词：AGEs ; advanced glycation end products ; DM ; diabetes mellitus ; ETS ; electron transfer system ; MG ; methylglyoxal ; OXPHOS ; oxidative phosphorylation ; PAMAM G3 ; generation 3 of poly(amido)amine dendrimer ; RCR ; respiratory control ratio ; ROS ; reactive oxygen s
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：1 July, 2012
• 卷：430
• 期：1-2
• 页码：258-265
• 文件大小：381 K

摘要

Poly(amido)amine (PAMAM) dendrimer G3 was investigated for its ability to support the proper functioning of rat heart mitochondria exposed to hyperglycemia, in both the in vitro and in vivo experiments. The main aims of this study were to check whether PAMAM G3 dendrimer improves the efficiency of the impaired respiration of rat heart mitochondria.

This study showed that mitochondria isolated from animals studied in different seasons respond to G3 (100 渭M) exposure to a different extent. Probably, seasonal variations had the impact on rat metabolism and consequently on the received data. The used biological samples formed a heterogenous group and therefore the obtained results were not pooled together but treated separately. Nevertheless, the in vitro part of this study revealed that PAMAM G3 could be successfully used in the protection of heart mitochondria against MG-induced impaired respiratory activity. Despite these promising data, the protective effect of G3 was not confirmed in the in vivo experiment. This study revealed that dendrimer G3 (20 mg/kg bw) is toxic and very high mortality among the animals administered with G3 did not allow to perform a reliable data analysis.