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

Abstract

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.

Polyphenon-60 ameliorates metabolic risk factors, oxidative stress, and proinflammatory cytokines and modulates apoptotic proteins to protect the heart against streptozotocin-induced apoptosis

“…This finding agrees with the ability of EGCG to significantly decrease reactive oxygen species (ROS) and cytosolic Ca 2þ and to prevent alterations in the protein expression of the adherens molecules b-catenin and N-cadherin and the gap junction protein connexin 43 in cardiac cells [56]. Green tea significantly reduces the serum biomarker levels, increases the antioxidants levels in cardiac tissue and restores electrocardiographic changes compared with the isoproterenol-only-treated group [57] as well as reduces cyclophosphamide-induced myocardial toxicity [58]. These data clearly show that PP-60 is effective against cardiac stress.…”

Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

“…In another study with pure EGCG, a single 100 mg/kg/i.p significantly increased serum ALT levels but not mortality within 24 h. A single treatment with 150 and 300 mg/kg/i.p led to mortality of male CD-1 mice, in less than 24 h of treatment [14] and male CF-1 mice, treated once with 200 and 400 mg/kg/i.p, 4 out of 5 mice died in 2–3 days and less than 24 h, respectively [62] . Wistar albino rats were orally treated with 100 and 500 mg/kg/p.o/day of GTE for 30 days [2] reporting no toxicity. Nevertheless, in this study [2] , EGCG content from aqueous extract is not indicated.…”

“…Wistar albino rats were orally treated with 100 and 500 mg/kg/p.o/day of GTE for 30 days [2] reporting no toxicity. Nevertheless, in this study [2] , EGCG content from aqueous extract is not indicated. In another report, a single lethal dose of 200 mg/kg/i.p of EGCG (>98% purity) triggered hepatotoxicity, suppressed major antioxidant enzymes and Nrf2 rescue pathway, a non-lethal dose of repeated 75 mg/kg/i.p/day treatment for 5 consecutive days, markedly decreased the anti-oxidant enzymes and activated the Nrf2 rescue response, while a consecutive 7 day MTD of 45 mg/kg/i.p/day did not reproduce the above changes [74] .…”

Protective Effect of Ellagic Acid Against Lead Induced Myocardial Toxicity

“…The myocardial damage was determined by scoring method based on the severity: no change -0 score, mild -1 score (focal myocytes damage, small multifocal degeneration with slight degree of inflammation), moderate -2 score (extensive myofibrillar degeneration) and marked -3 score (necrosis with diffuse inflammation). 22,23…”