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Protective effect of melatonin on the development of abdominal aortic aneurysm in a rat model
Li Tang1, Zhuangzhuang Cong1, Shuangying Hao2
1Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Background:
Oxidative injury, inflammation, and apoptosis are involved in the progression of abdominal aortic aneurysm (AAA). Melatonin (MLT) has been reported with an effective antioxidant activity. The objective of the present study was to investigate whether MLT could suppress the development of AAA.
Methods:
The AAA model was introduced by intraluminal perfusion of elastase in rats. All rats were divided into three groups as follows: (1) sham; (2) AAA + vehicle; and (3) AAA + MLT. Daily administration of MLT (10 mg/kg/d) or vehicle started 3 d before the perfusion and continued for 28 d after perfusion. An ultrasound system was applied to measure the dilation of the aorta. Histologic assays were performed to evaluate the structure, morphology, and apoptotic cells of the aortas; biochemical assays to determine the levels of proteins and lipid peroxide, activities of superoxide dismutase and NADPH oxidases, and cell viability; dihydroethidium fluorescence staining and flow cytometry to detect the presence of reactive oxygen species, and/or cell apoptosis; and electron microscopy to observe the ultrastructure of mitochondria. Cell lines A7R5 and RAW 264.7 were used for in vitro experiments.
Results:
MLT treatment inhibited dilation of the aorta very likely through its antioxidant property; significantly reduced the levels of lipid peroxide, activities of NADPH oxidases, and content of reactive oxygen species; remarkably inhibited NF-κB signaling pathway and activities of matrix metalloproteinases triggered by elastase perfusion. As a result, the mitochondrion-dependent apoptosis was suppressed, cellular energy (ATP) supply was recovered, and mitochondrial morphology remained intact.
Conclusions:
Our results demonstrate the beneficial effects of MLT on inhibition of AAA formation, suggesting that MLT could be a potential agent for prevention of the development of human AAA.
Insights
Melatonin (MLT) effectively suppressed abdominal aortic aneurysm (AAA) development in rats by reducing oxidative stress and inflammation. This suggests MLT may be a potential therapeutic agent for preventing human AAA.
Area of Science:
- Vascular Biology
- Pharmacology
- Biochemistry
Background:
- Abdominal aortic aneurysm (AAA) progression involves oxidative injury, inflammation, and apoptosis.
- Melatonin (MLT) exhibits potent antioxidant properties.
- The study investigated MLT's potential to inhibit AAA development.
Purpose of the Study:
- To determine if melatonin (MLT) can suppress the development of abdominal aortic aneurysm (AAA).
- To evaluate the protective effects of MLT against AAA formation in a rat model.
Main Methods:
- An elastase-induced AAA model in rats was used, with groups receiving sham, vehicle, or MLT.
- Administration of MLT (10 mg/kg/d) or vehicle commenced before and continued after perfusion for 28 days.
- Aortic dilation, histology, biochemical assays, ROS detection, and mitochondrial ultrastructure were assessed.
Main Results:
- MLT treatment significantly inhibited aortic dilation, likely via its antioxidant effects.
- MLT reduced lipid peroxide levels, NADPH oxidase activity, and reactive oxygen species (ROS).
- MLT suppressed NF-κB signaling, matrix metalloproteinases, and mitochondrion-dependent apoptosis, preserving mitochondrial morphology and ATP supply.
Conclusions:
- Melatonin (MLT) demonstrated beneficial effects in inhibiting AAA formation.
- MLT's antioxidant and anti-inflammatory actions contribute to its protective effects against AAA.
- MLT shows potential as a preventive agent for human abdominal aortic aneurysm.
