Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Abstract

Context. Croton macrostachyus Hochst. ex Delile (Euphorbiaceae) has been used in traditional medicine to manage heart failure and other heart diseases in Ethiopia. Objective. To evaluate the antioxidant and cardioprotective activities of stem bark extract and solvent fractions of Croton macrostachyus on cyclophosphamide-induced cardiotoxicity in rats. Materials and Methods. DPPH free radical scavenging assay method was used to determine antioxidant activity whereas Sprague-Dawley rats were used to evaluate the cardioprotective activity. Except for the normal control, all groups were subjected to cyclophosphamide (200 mg/kg, i.p.) toxicity on the first day. Enalapril at 10 mg/kg was used as a reference. The hydromethanolic crude extract (100, 200, and 400 mg/kg) and aqueous and ethyl acetate fractions (100 and 200 mg/kg, each) were administered for 10 days. The cardioprotective activities were evaluated using cardiac biomarkers such as Troponin I, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), and histopathological studies of heart tissue. Results. Crude extract and ethyl acetate and aqueous fractions exhibited free radical scavenging activities at IC50 of 594 μg/mL, 419 μg/mL, and 716 μg/mL, respectively. Crude extract at 400 mg/kg decreased the levels of troponin, AST, ALT, and ALP to 0.29 ± 0.06 ng/mL, 103.00 ± 7.63 U/L, 99.80 ± 6.18 U/L, and 108.80 ± 8.81 U/L, respectively. In addition, ethyl acetate fraction at 200 mg/kg decreased the levels of troponin, AST, ALT, and ALP to 0.22 ± 0.02 ng/mL, 137.00 ± 14.30 U/L, 90.33 ± 6.13 U/L, and 166.67 ± 13.50 U/L, respectively, compared with the cyclophosphamide control group. Conclusions. Croton macrostachyus possesses cardioprotective activities and it could be a possible source of treatment for cardiotoxicity induced by cyclophosphamide.

<p>Protective Effect of <em>Croton macrostachyus</em> (Euphorbiaceae) Stem Bark on Cyclophosphamide-Induced Nephrotoxicity in Rats</p>

“…All treatment groups prevented increases in kidney-to-body weight ratio compared to cyclophosphamide-treated group. The antioxidant activity 24 of Croton macrostachyus might be the reason for the prevention of kidney and kidney-to-body weight increment.…”

“…Thus, the plant showed anti-bacterial, 21 anti-diarrheal, 13 anti-malarial, 22 anti-convulsant, 23 antidiabetic 16 and cardioprotective activity. 24 The phytochemical screening demonstrated that stem bark of Croton macrostachyus constituted major secondary metabolites such as, tannins, steroids, alkaloids, phenols, terpenoids, saponins, and flavonoids, which may be the reason for the plants' widespread pharmacological activity. 25 In Ethiopian traditional medicine, Croton macrostachyus has been widely used to manage renal diseases.…”

The Role of Antioxidants in Ameliorating Cyclophosphamide-Induced Cardiotoxicity

“…Ayza et al [62] Either sex of Sprague Dawley rats Animals were treated with a single dose of CP (200 mg/kg, i.p.) on the first day followed by hydromethanolic crude extract and solvent fractions of Croton macrostachyus for 10 days.…”

Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways

“…They were also found to activate a cellular redox defense mechanism by stimulating endogenous antioxidant fractions [32] and keep the cells from xenobiotic oxidative stress, DNA impairment, and apoptosis [33]. Much attention has been given to using plant chemicals as a defensive strategy to resolve cardiotoxicity triggered by DOX [34][35][36].…”