Comparison of the Neuroprotective Effects of Aspirin, Atorvastatin, Captopril and Metformin in Diabetes Mellitus

Abstract

Objective: The aim of this study was to investigate the effect of combined intake of a high dose of aspirin, atorvastatin, captopril and metformin on oxidative stress in the brain cortex and hippocampus of streptozotocin (STZ)-induced diabetic rats. Material and methods: Rats were randomly divided into the following 11 groups: control and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg) and/or atorvastatin (AT, 40 mg/kg) as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA) and (D + M + C + AT + ASA). The rats in treatment groups received drugs by gavage daily for six weeks. Serum lipid profile and levels of oxidative markers in the brain cortex and hippocampus tissues were evaluated. Results: The levels of malondialdehyde in the brain cortex and hippocampus in all the treated groups decreased significantly (p < 0.05). There was a significant increase in the total thiol concentration as well as catalase activity in treated rats in (M + AT), (M + C + ASA), (M + C + AT), (M + AT + ASA) and (M + C + AT + ASA) groups in cortex and hippocampus in comparison with the diabetic rats (p < 0.05). Also, the superoxide dismutase activity in all treated rats with medications was significantly increased compared to the diabetic rats (p < 0.05–0.01). Conclusion: Our findings showed that the combined use of high-dose aspirin, metformin, captopril and atorvastatin potentiated their antioxidant effects on the brain, and hence could potentially improve cognitive function with their neuroprotective effects on hippocampus.

Arabic version of the Hayling sentence completion test: scale validation, normative data and factors associated with executive functions in a sample of the Lebanese adults

“…These results contradict the literature that underlines the negative correlation between executive functions and aging [9]. However, they could be explained by the fact that many of the elderly participants reported taking metformin, aspirin, atorvastatin, and angiotensin converting enzyme inhibitors (ACEi) or ARBs, which, when taken as a combination, could potentiate the anti-oxidant effect of each drug, enhancing their neuroprotective effects on the hippocampus [44].…”

Oxidative/Antioxidative Status in Patients after Myocardial Infarction and in Those without Cardiovascular Event Depending on Anthropometric Factors Defining Body Weight

“…Aspirin, statins, angiotensin converting enzyme II (Ang II) inhibitor, and metformin are commonly used in the secondary prevention of cardiovascular events and treatment of concomitant diseases; they also exhibit many pleiotropic effects [46]. The Paseban et al’s [47] study showed that the combined use of the above-mentioned drugs enhances their antioxidant effect. Aspirin has an antioxidant effect by reducing the production of free radicals, such as peroxide, and prevents a decrease in the activity of antioxidant enzymes (catalase and peroxide dismutase) [48].…”

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

“…Although preclinical studies using animal models suggest that aspirin can interfere in the development of insulin resistance, the results from human clinical trials are less convincing, with ASA alone having a lower effect on metabolic damage than combined therapy. For example, administration of aspirin combined with common diabetes medications potentiated their antioxidant effects and reduced oxidative stress [55]. Furthermore, the increased risk of gastrointestinal bleeding following administration of aspirin limits its use as long-term pharmacotherapy [56].…”