Brazil nut (Bertholletia excelsa) and metformin abrogate cardiac complication in fructose/STZ-induced type 2 diabetic rats by attenuating oxidative stress and modulating the MAPK-mTOR/NFkB/IL-10 signaling pathways.

ABSTRACT

Background: The global prevalence of diabetic heart complication has been on the increase, and some of the drugs that are currently used to treat diabetes mellitus (DM) have not been able to mitigate this complication. Objective: This study determines the effect of Brazil nut (Bertholletia excelsa) and metformin on diabetic cardiomyopathy (DCM) in fructose/streptozotocin (STZ)-induced type 2 diabetic rats and also characterizes using Gas Chromatography Mass Spectrophotometry and Fourier Transform Infrared the bioactive compounds in 50% aqueous ethanol extract of Brazil nut. Design: After inducing type 2 DM, 30 male albino Wistar rats were separated into five groups that comprised of six rats per group, and they were treated as follows groups 1 (Control) and 2 (Diabetic control) rats received rat pellets and distilled water; group 3 (Diabetic + Brazil nut) received rat pellets and Brazil nut extract (100 mg/kg, orally) dissolved in distilled water, group 4 (Diabetic + metformin) received metformin (100 mg/kg, orally) dissolved in distilled water, while group 5 (Diabetic + Brazil nut + metformin) received oral administrations of Brazil nut (100 mg/kg) and metformin (100 mg/kg) dissolved in distilled water. This study lasted for 6 weeks. The dose of Brazil nut used was selected from our pilot study on the minimum therapeutic dose of different concentrations of Brazil nut extract. Results: STZ administration induced insulin resistance, hyperglycemia, loss of weight, dyslipidemia, oxidative stress, inflammation, apoptosis, alteration of mammalian target of rapamycin, mitogen-activated protein kinase, heart function markers (creatine kinase MB, lactate dehydrogenase, and aspartate amino transaminase), and heart histology of the diabetic control, which was ameliorated after treatment with Brazil nut and metformin, but their combined treatment was better than the single treatments. Conclusion: This study shows that Brazil nut contains several bioactive compounds that support its biological properties as well as its candidature as a complementary therapy to metformin in mitigating cardiac complications arising from DM in rats.