Could allicin alleviate trastuzumab-induced cardiotoxicity in a rat model through antioxidant, anti-inflammatory, and antihyperlipidemic properties?

• Published in: Life sciences (1973) 2022-08, Vol.302, p.120656, Article 120656
• Main Authors: Mousa, Ayman M., Soliman, Khaled E.A., Alhumaydhi, Fahad A., Almatroudi, Ahmad, Allemailem, Khaled S., Alsahli, Mohammed A., Alrumaihi, Faris, Aljasir, Mohammad, Alwashmi, Ameen S.S., Ahmed, Ahmed A., Khan, Arif, Al-Regaiey, Khalid A., AlSuhaymi, Naif, Alsugoor, Mahdi H., Aljarbou, Walid A., Elsayed, Abulmaaty M.
• Format: Article
• Language: English
• Subjects: Allicin; Antiapoptotic; Antifibrotic; Antihyperlipidemic; Antioxidants; Apoptosis; Cardiotoxicity; Collagen; Flow cytometry; Garlic; IL-1β; Inflammation; Interleukin 6; Molecular modelling; Myocardium; Toxicity; Trastuzumab; Tumor necrosis factor-α
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120656

Although trastuzumab (TZB)-induced cardiotoxicity is well documented and allicin (one of the main active garlic ingredients) has ameliorating effects against numerous causes of toxicities; however, the influence of allicin on TZB-induced cardiotoxicity has not been investigated yet. Therefore, the current work explored the potential cardioprotective structural, biochemical, and molecular mechanisms of allicin against TZB-induced cardiotoxicity in a rat's model. Forty rats were divided into four equal groups and treated for five weeks. The control group (G1) received PBS, the allicin group (G2) received allicin (9 mg/kg/day), the TZB group (G3) received TZB (6 mg/kg/week), and the allicin+TZB group (G4) received 9 mg of allicin/kg/day +6 mg of TZB/kg/week. Heart specimens and blood samples were processed for histopathological, immunohistochemical, biochemical, and molecular investigations to determine the extent of cardiac injury in all groups. The myocardium of G3 revealed significant increases in the numbers of inflammatory and apoptotic cells and the area percentage of collagen fibers and TNF-α immunoexpression compared with G1 and G2. Besides, qRT-PCR analysis exhibited significant reductions of SOD3, GPX1, and CAT expressions with significant increases in TNFα, IL-1β, IL-6, cTnI, cTnT, and LDH expressions. Additionally, flow cytometry analysis demonstrated a significant elevation in the apoptotic and ROS levels. In contrast, allicin+TZB cotherapy in G4 ameliorated all previous changes compared with G3. The current study proves that allicin could be used as a novel supplementary cardioprotective therapy to avoid TZB-induced cardiotoxicity via its anti-inflammatory, antifibrotic, antioxidant, antihyperlipidemic, and antiapoptotic properties. [Display omitted] •Trastuzumab-induced cardiotoxicity in female rats.•Allicin decreased cardiac inflammatory cells, fibrosis, TNF-α IE, and apoptosis.•Allicin decreased lipid profile, pro-inflammatory cytokines, and cardiac enzymes.•Allicin could be a novel adjuvant therapy against trastuzumab cardiotoxicity.