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Exenatide (a GLP-1 agonist) improves the antioxidative potential of in vitro cultured human monocytes/macrophages.

Bułdak Ł, Łabuzek K, Bułdak RJ, Machnik G, Bołdys A, Okopień B - Naunyn Schmiedebergs Arch. Pharmacol. (2015)

Bottom Line: According to our findings, exenatide reduced ROS and malondialdyhyde (MDA) level by decreasing the expression of ROS-generating NADPH oxidase and by increasing the expression and activities of SOD and GSH-Px.We also showed that this effect was significantly inhibited by exendin 9-39 (a GLP-1 antagonist) and blocked by H89.This effect relied on the stimulation of GLP-1 receptor.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Medykow 18, 40-752, Katowice, Poland, lbuldak@gmail.com.

ABSTRACT
Macrophages are dominant cells in the pathogenesis of atherosclerosis. They are also a major source of reactive oxygen species (ROS). Oxidative stress, which is particularly high in subjects with diabetes, is responsible for accelerated atherosclerosis. Novel antidiabetic drugs (e.g., glucagon-like peptide-1 (GLP-1) agonists) were shown to reduce ROS level. Therefore, we conceived a study to evaluate the influence of exenatide, a GLP-1 agonist, on redox status in human monocytes/macrophages cultured in vitro, which may explain the beneficial effects of incretin-based antidiabetic treatment. Human macrophages obtained from 10 healthy volunteers were in vitro subjected to the treatment with GLP-1 agonist (exenatide) in the presence of lipopolysaccharide (LPS), antagonist of GLP-1 receptors (exendin 9-39), or protein kinase A inhibitor (H89). Afterwards, reactive oxygen species, malondialdehyde level, NADPH oxidase, and antioxidative enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase] expression was evaluated. Finally, we estimated the activity of the abovementioned enzymes in the presence of H89. According to our findings, exenatide reduced ROS and malondialdyhyde (MDA) level by decreasing the expression of ROS-generating NADPH oxidase and by increasing the expression and activities of SOD and GSH-Px. We also showed that this effect was significantly inhibited by exendin 9-39 (a GLP-1 antagonist) and blocked by H89. Exenatide improved the antioxidative potential and reduced oxidative stress in cultured human monocytes/macrophages, and this finding may be responsible for the pleiotropic effects of incretin-based therapies. This effect relied on the stimulation of GLP-1 receptor.

No MeSH data available.


Related in: MedlinePlus

The viability of cultured monocytes/macrophages assessed by the 0.4 % trypan blue exclusion test and MTT
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Fig1: The viability of cultured monocytes/macrophages assessed by the 0.4 % trypan blue exclusion test and MTT

Mentions: Results are expressed as the mean ± standard deviation (SD). The normality of distribution was checked by means of Shapiro–Wilk’s test. The statistical analysis of the data was performed using one-way ANOVA followed by the post hoc Tukey honestly significant difference test or Kruskal–Wallis test with Mann–Whitney tests according to parameter distribution. The Bonferroni adjustment was applied for multiple comparisons. Differences were considered significant for p < 0.05. Statistical analysis was performed using a SPSS statistical software package (SPSS 16.0 for Windows).


Exenatide (a GLP-1 agonist) improves the antioxidative potential of in vitro cultured human monocytes/macrophages.

Bułdak Ł, Łabuzek K, Bułdak RJ, Machnik G, Bołdys A, Okopień B - Naunyn Schmiedebergs Arch. Pharmacol. (2015)

The viability of cultured monocytes/macrophages assessed by the 0.4 % trypan blue exclusion test and MTT
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537507&req=5

Fig1: The viability of cultured monocytes/macrophages assessed by the 0.4 % trypan blue exclusion test and MTT
Mentions: Results are expressed as the mean ± standard deviation (SD). The normality of distribution was checked by means of Shapiro–Wilk’s test. The statistical analysis of the data was performed using one-way ANOVA followed by the post hoc Tukey honestly significant difference test or Kruskal–Wallis test with Mann–Whitney tests according to parameter distribution. The Bonferroni adjustment was applied for multiple comparisons. Differences were considered significant for p < 0.05. Statistical analysis was performed using a SPSS statistical software package (SPSS 16.0 for Windows).

Bottom Line: According to our findings, exenatide reduced ROS and malondialdyhyde (MDA) level by decreasing the expression of ROS-generating NADPH oxidase and by increasing the expression and activities of SOD and GSH-Px.We also showed that this effect was significantly inhibited by exendin 9-39 (a GLP-1 antagonist) and blocked by H89.This effect relied on the stimulation of GLP-1 receptor.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Medykow 18, 40-752, Katowice, Poland, lbuldak@gmail.com.

ABSTRACT
Macrophages are dominant cells in the pathogenesis of atherosclerosis. They are also a major source of reactive oxygen species (ROS). Oxidative stress, which is particularly high in subjects with diabetes, is responsible for accelerated atherosclerosis. Novel antidiabetic drugs (e.g., glucagon-like peptide-1 (GLP-1) agonists) were shown to reduce ROS level. Therefore, we conceived a study to evaluate the influence of exenatide, a GLP-1 agonist, on redox status in human monocytes/macrophages cultured in vitro, which may explain the beneficial effects of incretin-based antidiabetic treatment. Human macrophages obtained from 10 healthy volunteers were in vitro subjected to the treatment with GLP-1 agonist (exenatide) in the presence of lipopolysaccharide (LPS), antagonist of GLP-1 receptors (exendin 9-39), or protein kinase A inhibitor (H89). Afterwards, reactive oxygen species, malondialdehyde level, NADPH oxidase, and antioxidative enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase] expression was evaluated. Finally, we estimated the activity of the abovementioned enzymes in the presence of H89. According to our findings, exenatide reduced ROS and malondialdyhyde (MDA) level by decreasing the expression of ROS-generating NADPH oxidase and by increasing the expression and activities of SOD and GSH-Px. We also showed that this effect was significantly inhibited by exendin 9-39 (a GLP-1 antagonist) and blocked by H89. Exenatide improved the antioxidative potential and reduced oxidative stress in cultured human monocytes/macrophages, and this finding may be responsible for the pleiotropic effects of incretin-based therapies. This effect relied on the stimulation of GLP-1 receptor.

No MeSH data available.


Related in: MedlinePlus