Swimming exercise improves vascular function and mitigates cardiac apoptotic response via Bcl-2 and Caspase-3 pathway in streptozotocin-induced diabetic rats: in vivo and in silico molecular docking study.

BACKGROUND: Diabetes mellitus (DM) can result in impaired blood flow and apoptosis. This study investigated the in vivo and in silico effects of Streptozotocin-induced DM (STZ-DM) on vascular endothelial functions and cardiac apoptotic markers after swimming exercise. METHODS: This controlled experimental study was conducted using Wistar rats of both sexes. The rats were assigned to five groups (n = 7 each): control (C), diabetic (STZ-Dm), exercise (Ex), diabetic + exercise (STZ-Dm + Ex), and diabetic + insulin (STZ-Dm + In). DM was induced using streptozotocin (65 mg/kg IP), while 6 IU of insulin was administered (IP) to rats in the STZ-Dm + In group. The exercise groups were put through a structured swimming exercise for 27 days, after which blood samples and hearts were collected for biochemical and cardiac apoptotic marker determination, respectively. Molecular docking simulations of STZ on vascular and apoptotic markers were also conducted. RESULTS: Regular swimming exercise minimized hyperglycemia, reduced angiotensin converting enzyme activity, endothelin-1 levels, and raised nitric oxide level in STZ-Dm + Ex compared with STZ-Dm only group (p < 0.05). Hyperglycemia in STZ-Dm + Ex were comparable with control and STZ-Dm + In groups. Cardiac level of Bcl-2 was increased, while caspase-3, serum C-reactive protein, and myoglobin levels were reduced in Ex, STZ-Dm + Ex, and STZ-Dm + In groups when compared with the STZ-Dm group. STZ exhibited the strongest binding energy with ACE [1O86] (-6.9 kcal/mol], endothelin receptor A [5X93(-6.3 kcal/mol)], and less with iNOS, [3E7G, (-5.8 kcal/mol)], myoglobin [1A6M (-5.2 kcal/mol)], caspase-3 [1PAU (-4.6 kcal/mol)] and Bcl-2 [4LVT(-4.4 kcal/mol)]. CONCLUSIONS: Swimming exercise mitigates the adverse effects of STZ-DM, probably by improving endothelial functions and reducing cell damage via the Bcl-2 and caspase-3 pathway.