Pharmacodynamic Interaction of Green Tea Extract with Hydrochlorothiazide against Cyclophosphamide-Induced Myocardial Damage.

OBJECTIVE: Treatment of ischemic hypertensive patients with hydrochlorothiazide can precipitate cardiac arrhythmias. Green tea by virtue of its antioxidant potential is responsible for cardio-protective activity. The present study was undertaken to evaluate the pharmacodynamic interaction of green tea extract with hydrochlorothiazide against cyclophosphamide-induced myocardial toxicity. MATERIALS AND METHODS: Rats were treated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of green tea extract in alone and interactive groups for 10 days. Standard, high, and low dose of interactive groups received hydrochlorothiazide (10 mg/kg, p.o.) for last 7 days. Apart from normal control, all other groups were subjected to cyclophosphamide (200 mg/kg, i.p.) toxicity on day first and the effects of different treatments were evaluated by changes in electrocardiographic parameters, serum biomarkers, and tissue antioxidant levels. Apart from that, lipid profile and histological studies were also carried out. RESULTS: Compared to cyclophosphamide control group, both high and low dose of green tea exhibited significant decrease in serum biomarkers and increase in tissue antioxidant levels. Green tea treatment was also responsible for significant improvement in echocardiography (ECG) parameter, lipid profile, and histological score. Incorporation of high and low dose of green tea with hydrochlorothiazide-exhibited significant protection compared to hydrochlorothiazide-alone-treated group. CONCLUSION: The present findings clearly suggested that green tea extract dose dependently reduces cyclophosphamide-induced myocardial toxicity. Green tea when combined with hydrochlorothiazide can reduce the associated side effects and exhibits myocardial protection.

Effect of daidzein on cisplatin-induced hematotoxicity and hepatotoxicity in experimental rats.

OBJECTIVE: The objective of the study was to investigate the effect of daidzein flavonoid on cisplatin (CP)-induced hematotoxicity and hepatotoxicity in experimental rats. MATERIALS AND METHODS: The Wistar rats were randomly divided into four equal groups: Normal (saline 1 ml p.o.), CP (7.5 mg/kg once intraperioteneally on 16th day), test group of low dose (combination of CP and daidzein 20 mg/kg p.o. for 21 days), and test group of high dose (combination of CP and daidzein 40 mg/kg p.o. for 21 days). Blood samples were collected on 22nd day from each rat and subjected for evaluation of hematological parameters such as red blood corpuscles (RBC), white blood corpuscles, hemoglobin (Hb) and platelets, and serum biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver of each rat was excised and subjected for antioxidants evaluation such as malonyl dialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, and histopathological study. RESULTS: Daidzein had a significant (P < 0.001) beneficial role in CP-induced hemotoxicity by increasing RBC, Hb, packed cell volume, and platelets. Daidzein also exhibited a significant (P < 0.001) protection against CP-induced hepatotoxicity by decreasing ALT, AST, ALP, and MDA level and by elevating the GSH, SOD, and catalase. CONCLUSIONS: Daidzein attenuates CP-induced oxidative stress on blood cells and antioxidants in rats.

Cardioprotective effect of curcumin and piperine combination against cyclophosphamide-induced cardiotoxicity.

OBJECTIVE: Curcumin is a well-established cardioprotective phytoconstituent, but the poor bioavailability associated with it is always a matter of therapeutic challenge. The present study was undertaken to increase the therapeutic efficacy of curcumin by combining with bio-enhancer like piperine against cyclophosphamide (CP)-induced cardiotoxicity in rats. MATERIALS AND METHODS: Rats (n = 8) were treated with curcumin (200 mg/kg, p.o.) alone and different dose combination of curcumin (100, 50, 25 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 10 days. All the treated groups were subjected to CP (200 mg/kg, i.p.) toxicity on day 1. Twenty-four hours after the last treatment, the effects were evaluated by changes in electrocardiographic (ECG) parameters, serum biomarkers, lipid profile, tissue antioxidants, and histopathological examination. Serum and tissue homogenate parameters were measured by semi-autoanalyzer and spectrophotometer, respectively. Results obtained were assessed by one-way analysis of variance followed by Tukey-Karmer multiple comparison test. RESULTS: Incorporation of piperine with the doses of 50 and 25 mg/kg with curcumin exhibited significant beneficial effect compared to curcumin alone-treated group. The best effective group was a combination of curcumin 50 mg/kg with piperine 20 mg/kg which showed extremely significant (P < 0.001) decrease and increase in ECG and serum biomarker level, respectively, and moderate significant (P < 0.01) decrease in lipid profile, antioxidant levels, and histopathological score, compared to curcumin alone-treated group. CONCLUSION: From this study, it can be concluded that a novel dose combination of curcumin (50 mg/kg) with piperine (20 mg/kg) exhibited profound cardioprotection compared to curcumin (200 mg/kg) alone-treated group.

Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against ischemia-reperfusion injury-induced myocardial infarction.

Globally, the rate of development of myocardial diseases and hypertension is very common, which is responsible for incremental morbidity and mortality statistics. Treatment of ischemic hypertensive patients with diuretics such as hydrochlorothiazide (HCTZ) can precipitate myocardial infarction due to hypokalemia. This study was undertaken to evaluate the pharmacodynamic interaction of green tea extract (GTE) with HCTZ against ischemia-reperfusion induced myocardial toxicity. Wistar albino rats of either sex were taken and pretreated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of GTE for 30 days. Standard, high and low dose of interactive groups received HCTZ (10 mg/kg, p.o.) for last 7 days. Ischemia-reperfusion injury was induced by modified Lagendorff apparatus, and the effect of different treatments was evaluated by percentage recovery in terms of heart rate and developed tension, serum biomarkers, and heart tissue antioxidant levels. Prophylactic treatment groups, such as high and low dose of GTE and their interactive groups with HCTZ, exhibited significant percentage recovery in terms of heart rate and developed tension. Apart from that, significant increase in superoxide dismutase and catalase, decrease in thiobarbituric acid reactive species in heart tissue, as well as significant decrease in serum lactate dehydrogenase, creatinine phosphokinase-MB and N-acetylcysteine levels have also been documented. The present findings clearly suggest that GTE dose-dependently reduces myocardial toxicity due to ischemia, and combination with HCTZ can reduce the associated side-effects and exhibits myocardial protection.