Key result
Allyl isothiocyanate ameliorated acute cardiotoxicity and oxidative stress induced by doxorubicin (which caused 40% mortality alone) via increasing Nrf2 and HO-1 expression.
Why the study?
Cardiotoxicity restricts the clinical benefit of doxorubicin, prompting investigation into whether the natural antioxidant and anti-inflammatory agent allyl isothiocyanate provides cardioprotection.
Does allyl isothiocyanate prevent doxorubicin-induced acute cardiotoxicity in a rat model?
Does allyl isothiocyanate prevent doxorubicin-induced acute cardiotoxicity in a rat model?
Allyl isothiocyanate demonstrates cardioprotective effects against doxorubicin-induced acute toxicity in rats by reducing oxidative stress and inflammation.
Does not support clinical use of AITC; leaves open human translation of Nrf2/HO-1 cardioprotection.
Doxorubicin (DOX) is an effective anthracycline chemotherapeutic drug. Nevertheless, the cardiotoxicity adverse effect restricts its clinical benefit. Allyl isothiocyanate (AITC) is a natural antioxidant and anti-inflammatory agent. In the present study, we investigated the effect of AITC on cardiotoxicity of DOX. Thirty-two adult male albino rats were divided into four groups; control, AITC, DOX, and AITC + DOX. AITC was administrated orally (25 mg/kg/day) for 7 days, and DOX was given as a single i.p. injection (15 mg/kg) on the third day. Mortality rate was observed during the experiment. Cardiac toxicity markers (lactate dehydrogenase (LDH), creatine kinase (CK-MB), and cardiac Troponin I (cTn-I)) were evaluated in serum samples obtained from all groups after 48 hours of DOX injection. DOX-treated group showed 40% mortality and a significant increase in cardiac enzymes. This increase was accompanied by degenerated cardiomyocytes, and inflammatory cells infiltrates. Interestingly, AITC administration alleviated myocardial oxidative stress induced by DOX as attenuated the increase in malondialdehyde (MDA), and nitric oxide (NO) while resulted in elevations of the antioxidant reduced glutathione (GSH) level as well as superoxide dismutase (SOD) activity. Furthermore, the inflammatory cytokine, TNF-α, was reduced upon administration of AITC with DOX. The cardio-protection of AITC is attributed to increase the expression of cytoprotective nuclear factor erythroid 2-related factor 2 (Nrf2). Subsequently, heme oxygenase 1 (HO-1) level was elevated by AITC to correct the oxidative stress induced by DOX in the heart. Accordingly, AITC ameliorated acute cardiotoxicity associated with DOX treatment via attenuation of oxidative stress and the induced-tissue inflammatory injury. Abbreviations: DOX: doxrubicin; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase 1; AITC: ally isothiocyanate; MDA: malondialdehyde; SOD: superoxide dismutase; GSH: reduced glutathione; TNF-α: tumor necrosis factor alpha.
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Waz et al. (2021) studied Doxorubicin acute toxicity (n=32). Allyl isothiocyanate (AITC) vs. Doxorubicin alone was evaluated on Mortality rate and cardiac toxicity markers. Allyl isothiocyanate ameliorated acute cardiotoxicity and oxidative stress induced by doxorubicin (which caused 40% mortality alone) via increasing Nrf2 and HO-1 expression.
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