Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats

AIM: We aimed to investigate the possible cardioprotective effects of paricalcitol (PR), its vitamin D receptor agonist, and vitamin D 3 (VIT-D3) on an experimental model of doxorubicin (DX) cardiotoxicity by 99m Tc-PYP scintigraphy, electrocardiographic (ECG) and biochemical methods.METHOD: Forty-two male Wistar/Albino rats (250-300 g; aged 10-12 weeks) were randomly separated into six groups, namely into control (CN), doxorubicin (DX), paricalcitol (PR), vitamin D 3 (VIT-D 3 ), paricalcitol + doxorubicin (PR+DX), and vitamin D 3 + doxorubicin (VIT-D 3 +DX) groups.Cardiotoxicity was induced by three doses of DX (18 mg/kg, i.p.) at 24-hour intervals on days 18, 19 and 20.PR (0.5 ug/ kg, i.p) and VIT-D 3 (5,000 IU/kg, i.p) were injected for 20 days before and after the application of DX (18 mg/kg, i.p.).On day 21 of the experiment, biochemical parameters [tumor necrosis factor TNF-alpha (TNF-α); interleukin-6 (IL-6), nitric oxide (NO), and cardiac troponin T (cTnT)], as well as ECG and scintigraphic ( 99m Tc-PYP) features were assessed.RESULTS: Compared to CN, DX significantly raised TNF-α, IL-6, and NO in heart tissue, cTnT in serum, 99m Tc-PYP uptake in the myocardium, and ECG parameters, specifically QRS complex duration, QT interval duration, and ST-segment amplitude, while also reducing heart rate (p<0.001).Pretreatment with PR and VIT-D 3 mitigated these abnormalities produced by DX in the heart (p<0.001).CONCLUSION: Results show that vitamin D receptor agonist paricalcitol and vitamin D protect against DX-induced cardiotoxicity through anti-inflammatory and antioxidant effects (Fig. 4, Ref. 59).