The chemotherapeutic and immunosuppressive agent cyclophosphamide has previously been shown to induce complications within the setting of bone marrow transplantation. More recently, cardiotoxicity has been shown to be a dose-limiting factor during cyclophosphamide therapy, and cardiooncology is getting wider attention. Though mechanism of cyclophosphamide-induced cardiotoxicity is not completely understood, it is thought to encompass oxidative and nitrative stress. As such, this review focuses on antioxidants and their role in preventing or ameliorating cyclophosphamide-induced cardiotoxicity. It will give special emphasis to the cardioprotective effects of natural, plant-derived antioxidants that have garnered significant interest in recent times.

Background: Societies in developing countries use traditional medicine as alternatives for management of pain and inflammation. The plant Cucumis ficifolius has been used in Ethiopia to treat many ailments including inflammation and pain. The objective of this study was to evaluate the antinociceptive and anti-inflammatory activities of the crude root extract and solvent fractions of C. ficifolius . Methods: The analgesic activity of crude extract and solvent fractions of C. ficifolius was evaluated with acetic acid-induced writhing, hot plate, and formalin-induced paw licking tests. The anti-inflammatory effect of crude methanolic root extract and solvent fractions of C. ficifolius was evaluated using carrageenan-induced paw edema. The crude extract was given at 200, 400 and 800 mg/kg. Butanol and aqueous fractions were given at 100 and 200 mg/kg doses. The negative control groups were treated with distilled water (10 mL/kg). Standard drugs used were acetylsalicylic acid (ASA) in acetic acid, formalin tests and carrageenan-induced paw edema and morphine (20 mg/kg) in hot plate test. Results: The crude extract, at its maximum dose, produced comparable analgesic activity (72.5%) to ASA in acetic acid writhing test. In the hot plate test, both the crude extract and solvent fractions exhibited a significant prolongation of nociception reaction time. Formalin test result indicated a significant reduction of mean lick time with maximal protection of 64% (early phase) and 83% (late phase). Aqueous and butanol fractions showed good analgesic activity in the three models. Inflammation was decreased by 69% with butanol (200 mg/kg); 71% (800 mg/kg) of crude extract and by 41% and 56% with the use of aqueous fraction at 100 and 200 mg/kg, respectively ( p <0.001). Conclusion: The present study indicates that the crude methanolic root extract, as well as butanol and aqueous solvent fractions, showed anti-nociceptive and anti-inflammatory activities.

Background Globally, cardiovascular diseases (CVDs) are becoming the major cause of death. Urtica simensis is one of endogenous plant which treats a wide range of disease conditions including heart diseases. However, there is limited information on safety and efficacy of the plant. Objective To evaluate the in vitro antioxidant, the in vivo cardioprotective activity of crude extract and solvent fractions of Urtica simensis leaves on cyclophosphamide-induced myocardial injury. Methods The cardioprotective activity of the crude extract, aqueous and hexane fraction of Urtica simensis leaves was evaluated based on anatomical, biochemical and histopathological methods. The in vitro antioxidant activity of the plant was also assayed in terms of free radical scavenging activity (RSA). Results Crude extract and solvent fractions of Urtica simensis significantly prevented the deleterious effect of cyclophosphamide on body weight (P<0.001), heart weight to body ratio (P<0.01), cardiac biomarkers including troponin I (P<0.01), alanine transaminase (ALT) (P<0.001), aspartate aminotransferase (AST) (P<0.01) and lipid profiles including triglycerides (P<0.001) and total cholesterol (P<0.01). The histopathological study confirmed presence of necrosis, oedema and haemorrhage on cyclophosphamide alone-treated groups while the 200mg/kg and 400mg/kg of the crude extract and aqueous fraction showed normal cardiocytes. The antioxidant assay of Urtica simensis plant exhibited free radical scavenging activity of inhibitory concentration of 50% (IC 50 ) for the crude extract with the values of 63.27µg/mL, aqueous fraction with the values of 136.38µg/mL and hexane fraction with the values of 258.70µg/mL. Conclusion Crude extract and solvent fractions of Urtica simensis leaves have cardioprotective activities. The cardioprotective effect could be attributed to the antioxidant activity of the plant extracts. However, this requires further in-depth understanding.

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.

Background: Cyclophosphamide is an alkylating antineoplastic agent and its major limitation is injury to normal tissue, leading to multiple organ toxicity, including kidney, heart, liver and reproductive toxicity. Croton macrostachyus (Euphorbiaceae) has been used in Ethiopian traditional medicine to manage renal diseases. Objective: The present study aims to assess the protective effect of the stem bark extract and solvent fractions of Croton macrostachyus on cyclophosphamide-induced nephrotoxicity in rats. Methods: Nephrotoxicity was induced using cyclophosphamide 200 mg/kg i.p injection on the first day of the experiment. The negative control groups were administered with cyclophosphamide alone (200 mg/kg, i.p.). The crude extracts were administered at three dose levels (100, 200, and 400 mg/kg), while aqueous and ethyl acetate fractions were given at two dose levels (100 and 200 mg/kg). Excepting the normal control, all groups were subjected to cyclophosphamide toxicity on the first day. Results: Treatment with crude extract 100 mg/kg and ethyl acetate fraction significantly decreased kidney-to-body weight ratio (P < 0.001). In addition, treatment with Croton macrostachyus crude extract and solvent fractions significantly decreased serum blood urea nitrogen (BUN) level (P < 0.001). Treatment with 100 and 200 mg/kg of ethyl acetate fraction significantly decreased serum creatinine level. Histopathological results confirmed the protective effect of the crude extract and solvent fractions of Croton macrostachyus. Conclusion: Croton macrostachyus possesses nephroprotective activities and it could be a possible source of treatment for cyclophosphamide-induced nephrotoxicity.