Hemodynamic Changes Provoked through Intravascular Injection of the Echis carinatus Venom in Rats.

Echis carinatus (E. carinatus) is known for its hematological and nephrotoxic properties in the envenomed patients. Based on the limited data upon the cardiovascular changes associated with this dangerous venomous snake in Iran, the current study purposed to evaluate the venom-induced hemodynamic manifestations in rats. Venom (120 µg/kg) was administered intravenously within one minute through the left femoral vein, and the hemodynamic parameters were continuously recorded using a pressure transducer (MLT844, ADInstruments, Australia). The venom caused prominent hypotension leading to death a few minutes after a transient uprise in blood pressure. It also induced a decrease in heart and pulmonary rates, yet it had no arrhythmogenic properties. Additionally, pre-treatment with the pepsin-derived Iranian polyvalent antivenom (30 µl/Kg) completely neutralized the hemodynamic responses but had no effect when instilled two minutes after venom injection. Heparin (300 IU/kg) and epinephrine (1.5 µg/kg) prevented dramatic hypotension when used 10 minutes before venom instillation; however, atropine (1 mg/kg), dexamethasone (1 mg/kg), and ketorolac (10 mg/ml) had no effects. All treated rats were killed post-injection. Histologically, the lung was the most vulnerable organ with mononuclear infiltration, microcystic formation, and significant capillary congestion. Prominent renal pathological deterioration also occurred, including mesangial cell infiltration and diffuse bleeding, leading to acute tubular necrosis. Modest portal inflammation and vascular congestion were observed in the hepatic tissue of the envenomed rats. The crude venom of Iranian Echis carinatus caused hypotension leading to bradycardia, a decrease in pulmonary rate, and death without significant histological changes to the heart.

Doxorubicin Cytotoxicity in Combination with Soy Isoflavone Daidzein on MCF-7 Breast Cancer Cells

Introduction: Combination chemotherapy regimens offer a promising approach to the prevention of recurrence, metastasis and drug resistance during breast cancer management. Combined tumor therapy using natural substances is highly suggested. Daidzein is one of the major isoflavones in soy beans with anti-tumor activity but its effect in combination with common chemotherapeutic agents is still unclear. This study was designed to investigate whether daidzein increases the antitumor activity of doxorubicin against MCF-7 human breast cancer cells. Methods: The cytotoxic activity of doxorubicin, daidzein and a combination of the two drugs was determined at different concentrations using LDH release assay. The average values of each experiment were adjusted to the values determined from untreated controls and 50% inhibitory concentration (IC.) value for each drug was calculated by CompuSyn. In vitro interaction was also calculated using different combinations of doxorubicin and daidzein. Combination indices (CI) were calculated and combination index plot was constructed using the same software. Results: Analysis of the dose-effect curve showed that the treatment of MCF-7 cells with doxorubicin or daidzein for 24 h led to 50% cytotoxicity at 5.4 nM and 146.5 respectively. Conclusion: The Combination index plot showed CI >1 for all combinations used in this study which indicates antagonistic interactions between daidzein and doxorubicin. This study results have implications for patients with breast cancer under treatment with doxorubicin if they are taking daidzein as a dietary supplement.