Background: Cigarette smoking is a major risk factor for cardiovascular disease. Oxidative stress plays a central role in endothelial dysfunction and atherosclerosis. β‑hydroxybutyrate (β‑OHB), a ketone body, has been proposed to exert antioxidant and vascular protective effects. This study aimed to evaluate the effects of β‑OHB on aortic histopathology and von Willebrand Factor (vWF) levels in Wistar rats exposed to cigarette smoke.
Methods: This experimental randomized controlled animal study included 25 male Wistar rats divided into five groups: negative control (K−), positive control (K+; cigarette smoke exposure), and three treatment groups receiving β‑hydroxybutyrate‑(R)‑1,3‑butanediol monoester (DeltaG®, TDeltaS Global Inc., Orlando, FL, USA) at doses of 1.5 g/kg/day (P1), 3 g/kg/day (P2), and 6 g/kg/ day (P3). Rats were exposed to 40 cigarettes/day for 28 days. Aortic tissues were collected after euthanasia on day 28 for histopathological analysis and vWF measurement using ELISA. Data were analyzed using ANOVA with Fisher’s LSD post‑hoc test.
Results: β‑OHB significantly reduced aortic histopathological alterations compared to the smoke‑exposed control group (degeneration p = 0.001, hyperemia p = 0.002, hemorrhage p = 0.001, necrosis p = 0.000). vWF levels differed significantly among groups (p = 0.034), indicating improved endothelial function.
Conclusions: β‑OHB attenuates cigarette smoke‑induced aortic injury and improves endothelial function. These findings support its potential role as a cardiometabolic therapeutic strategy.
