Abstract
Oxidative stress and fibrosis foster the development of cardiovascular disease (CVD) in diabetes. Atorvastatin protects against cardiovascular diseases in diabetes patients. However, the mechanisms are not completely known. This study evaluated the impact of atorvastatin on vascular and myocardial oxidative stress, inflammation, and fibrosis in a model of diabetes. Male Wistar rats were assigned into four groups; control rats, atorvastatin-treated rats (Ator, 40 mg/kg given by oral gavage for 6 weeks), diabetes rats (DM, single IP 40 mg/kg streptozotocin), and diabetes rats treated with atorvastatin (DM + Ator). Serum and cardiac inflammatory, oxidant, and fibrotic markers were measured. Cardiac fibrosis was evaluated by Masson trichrome stain. Streptozotocin-induced diabetes as documented by the marked elevation in blood glucose. Levels of oxidant biomarkers of serum and cardiac nitrite, cardiac nitrate, and cardiac thiobarbituric acid reactive substances (TBARS) were increased in the DM group. The use of atorvastatin reduced nitrite and TBARS levels. Serum and cardiac inflammatory factors of endothelin-1 (ET-1) were elevated in the DM group, and the use of atorvastatin reduced these increases. Cardiac C-reactive protein tended to increase in the DM group and the use of atorvastatin reduced its level. Cardiac interstitial fibrosis was increased in the DM group with a parallel increase in the platelet-derived growth factor level. The use of atorvastatin reduced cardiac fibrosis. Diabetes was associated with an increase in serum and/or myocardial markers of oxidative stress, inflammation, and fibrosis. The use of atorvastatin reduced cardiac interstitial fibrosis and decreased cardiac oxidant and inflammatory biomarkers.
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This study was funded by the deanship of research (grant number 405/2021) at Jordan University of Science and Technology, Irbid, Jordan.
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Fadia Mayyas: conceptualization, software, validation, formal analysis, writing original draft, visualization, investigation, resources, project administration, and funding acquisition. Tala Algharram: methodology and data curation, resources, investigation, writing-review, and editing.
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An approval from the Animal Care and Use Committee (ACUC) at Jordan University of Science and Technology (JUST) was obtained, approval number 16/4/12/455.
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Mayyas, F., Al Gharram, T. Impact of atorvastatin on plasma and cardiac biomarkers of inflammation, oxidative stress, and fibrosis in a rat model of streptozotocin-induced diabetes. Naunyn-Schmiedeberg's Arch Pharmacol 396, 261–274 (2023). https://doi.org/10.1007/s00210-022-02318-z
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DOI: https://doi.org/10.1007/s00210-022-02318-z