Capsaicin Ameliorates the Cyclophosphamide-Induced Cardiotoxicity by Inhibiting Free Radicals Generation, Inflammatory Cytokines, and Apoptotic Pathway in Rats

Abstract

Cyclophosphamide is an antineoplastic agent that has a broad range of therapeutic applications; however, it has numerous side effects, including cardiotoxicity. Furthermore, chili peppers contain a substance called capsaicin, having antioxidant and anti-inflammatory effects. Thus, this research paper focuses on the potential mechanism of capsaicin’s cardioprotective activity against cyclophosphamide-induced cardiotoxicity by measuring the expression of oxidative and inflammatory marker such as interleukins and caspases. The following groups of rats were randomly assigned: only vehicle given for 6 days (control group); cyclophosphamide 200 mg/kg intraperitoneal on 4th day only (positive control group); capsaicin 10 mg/kg orally given for 6 days followed by cyclophosphamide 200 mg/kg on 4th day of treatment; capsaicin 20 mg/kg orally for six days followed by cyclophosphamide 200 mg/kg on 4th day of treatment; and maximum amount of capsaicin alone (20 mg/kg) orally for six days. Using ELISA kits, it was found that the cyclophosphamide administration significantly increased the levels of lactate dehydrogenase, troponin-I (cardiac cell damage marker), lipid peroxidation, triglyceride, interleukin-6, tumor necrosis factor-alpha, and caspase 3. However, it markedly reduced the antioxidant enzymes catalase and glutathione levels. Both doses of capsaicin could reverse cardiac cell damage markers, as shown by a significant decline in (lactate dehydrogenase and troponin-I). In addition, capsaicin significantly reduced the cytokine levels (interleukin-6 and tumor necrosis factor-alpha), caspase 3, lipid peroxidation, and triglycerides. However, capsaicin treatment significantly raised the antioxidant content of enzymes such as glutathione and catalase. The capsaicin-treated group restored the oxidative parameter’s imbalance and generated considerable protection against cardiomyocyte harm from cyclophosphamide in male Wistar rats. These protective effects might be beneficial against the negative impacts of cyclophosphamide when used to treat cancer and immune-mediated diseases.

Effects of rosmarinic acid on cyclophosphamide-induced nephrotoxicity in rats

“…A study conducted in mammalian heart tissue cells reported that excessive production of free oxygen radicals during CP therapy caused lipid peroxidation, and the resulting membrane damage disrupted the integrity of the myocardial membrane and caused dysfunction 10 . In his study, Shanholtz 16 .…”

“…On the eighth day, a single dose of CP (200 mg/kg) was administered intraperitoneally. The dosages of CP (Endoxan, 1 g vial containing IV infusion powder, Eczacıbaşı, Baxter Oncology GmbH Halle, Germany) and RA (536954-5 g, 96% Sigma-Aldrich Chemie Gmbh) used in this study were determined according to the literature review 9,10 .…”

New insights into the potential cardioprotective effects of telmisartan and nanoformulated extract of Spirulina platensis via regulation of oxidative stress, apoptosis, and autophagy in an experimental model

“…The present findings demonstrate that the levels of Bax and caspase-3 increase following Cyclo injection while the level of BcL2 declines; this initiates the apoptotic pathway, which is associated with the presence of oxidative stress and subsequent DNA damage. Ultimately, these events culminate in the activation of the mitochondrial apoptotic pathway through a reduction in the levels of antiapoptotic proteins ( Mahmoud et al, 2017 ; Ahmed et al, 2023 ). It has been demonstrated that 150 mg/kg/day of Cyclo markedly increase the proapoptotic proteins caspase-3 and caspase-9 in the cardiac tissues of Wistar rats ( Adeyemi et al, 2024 ).…”

The Impact of Metformin on the Development of Hypothyroidism and Cardiotoxicity Induced by Cyclophosphamide, Methotrexate, and Fluorouracil in Rats

“…The previous literature has extensively reported that the administration of cyclophosphamide and fluorouracil can induce cardiotoxic effects, as indicated by the observed increase in troponin I and CK-MB concentrations [ 56 , 57 , 58 ]. The current study evaluated the concentrations of troponin I, creatine kinase (CK), and creatine kinase-MB (CK-MB) following CMF interventions.…”