Abstract
Both oxidative stress and the exacerbated generation of advanced glycation end products (AGEs) have crucial roles in the onset and progression of diabetic complications. Curcumin has antioxidant and antidiabetic properties; its combination with compounds capable of preventing the advanced glycation events, such as aminoguanidine, is an interesting therapeutic option to counteract diabetic complications. This study is aimed at investigating the effects of treatments with curcumin or aminoguanidine, alone or in combination, on metabolic alterations in streptozotocin-diabetic rats; the focus was mainly on the potential of these bioactive compounds to oppose the glycoxidative stress. Curcumin (90 mg/kg) or aminoguanidine (50 and 100 mg/kg), alone or in combination, slightly decreased glycemia and the biomarkers of early protein glycation, but markedly decreased AGE levels (biomarkers of advanced glycation) and oxidative damage biomarkers in the plasma, liver, and kidney of diabetic rats. Some novel insights about the in vivo effects of these bioactive compounds are centered on the triggering of cytoprotective machinery. The treatments with curcumin and/or aminoguanidine increased the activities of the antioxidant enzymes (paraoxonase 1, superoxide dismutase, and catalase) and the levels of AGE detoxification system components (AGE-R1 receptor and glyoxalase 1). In addition, combination therapy between curcumin and aminoguanidine effectively prevented dyslipidemia in diabetic rats. These findings demonstrate the combination of curcumin (natural antioxidant) and aminoguanidine (prototype therapeutic agent with anti-AGE activity) as a potential complementary therapeutic option for use with antihyperglycemic agents, which may aggregate beneficial effects against diabetic complications.
Highlights
The increasing prevalence of diabetes mellitus (DM) is a major health concern worldwide
An important contribution of this study was the triggering of cytoprotective machinery involved in the elimination of reactive oxygen species (ROS) and products/intermediates of advanced glycation by curcumin and aminoguanidine treatments, which go beyond their well-known per se antioxidant and anti-advanced glycation end products (AGEs) properties
The study of the underlying biochemical cascades that lead to advanced glycation and ROS generation in DM may provide new therapeutic strategies to attenuate or even prevent the progression of the diabetic complications
Summary
The increasing prevalence of diabetes mellitus (DM) is a major health concern worldwide. Diabetic complications have been associated with poor metabolic control and transient episodes of hyperglycemia, which result in the phenomenon called “metabolic memory” that causes relevant changes in many tissues. Oxidative Medicine and Cellular Longevity of the diabetic complications, even after the achievement of metabolic control; it is the collective result of several mechanisms, including the generation of advanced glycation products, oxidative stress, inflammation, and epigenetic changes [2]. From a clinical point of view, metabolic memory necessitates rapid intensive treatment of diabetic individuals following the diagnosis to quickly achieve metabolic control and minimize the long-term detrimental impacts of hyperglycemia in tissues [3, 4]. In addition to an intensive and more prompt therapy for glycemic control in diabetic individuals, novel combined therapeutic approaches have been suggested, including the use of bioactive agents capable of inhibiting the biochemical cascades triggered by advanced glycation, reactive oxygen species (ROS), and inflammation, effectively mitigating diabetic complications [5]
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