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.

The advancement in therapy has provided a dramatic improvement in the rate of recovery among cancer patients. However, this improved survival is also associated with enhanced risks for cardiovascular manifestations, including hypertension, arrhythmias, and heart failure. The cardiotoxicity induced by chemotherapy is a life-threatening consequence that restricts the use of several chemotherapy drugs in clinical practice. This article addresses the prevalence of cardiotoxicity mediated by commonly used chemotherapeutic and immunotherapeutic agents. The role of susceptible genes and radiation therapy in the occurrence of cardiotoxicity is also reviewed. This review also emphasizes the protective role of antioxidants and future perspectives in anticancer drug-induced cardiotoxicities.

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. 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. 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. 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.

Pomegranate can inhibit cytochrome P450 (CYP) 2C9 activity, which is largely responsible for the metabolism of sulfonylureas. The present study was undertaken to evaluate the pharmacokinetic and pharmacodynamic interaction of pomegranate and tolbutamide (TOL) against diabetic-induced complications. Diabetes was induced via administration of alloxan (150 mg/kg, intraperitoneally). Rats (n = 8) were treated with pomegranate juice (PJ) [3 mL/animal, per os (p.o.)], TOL (20 mg/kg, p.o.), and their combination for 4 weeks. Twenty-four hours after the last treatment, the pharmacodynamic interaction of PJ and TOL was evaluated by antinociceptive activity, electrocardiographic parameters, serum glucose, biomarkers, and lipid profile values. The influence of PJ on the pharmacokinetics of TOL was studied using the high performance liquid chromatography method. The combination of PJ and TOL resulted in a significant improvement against diabetic complications compared to the group treated with TOL alone. The combination group was found to be the best protective group by significant improvement of antinociceptive activity, restoration of electrocardiographic parameters, serum glucose, biomarkers, and lipid profile compared to the group treated with TOL alone. Results of the pharmacokinetic study revealed that PJ increases bioavailability and half-life, along with a decrease in clearance and elimination rate of TOL. From this study, it can be concluded that the combination of PJ and TOL exhibited profound protection compared to TOL alone against diabetic complications. The findings of pharmacokinetic interaction justified the results of pharmacodynamic interaction.

Diabetes mellitus is a common disease affecting millions of people worldwide. This disease is not limited to metabolic disorders but also affects several vital organs in the body and can lead to major complications. People with diabetes mellitus are subjected to cardiovascular complications, such as cardiac myopathy, which can further result in major complications such as diabetes-induced cardiac failure. The mechanism underlying diabetes-induced cardiac failure requires further research; however, several contributing factors have been identified to function in tandem, such as reactive oxygen species production, inflammation, formation of advanced glycation end-products, altered substrate utilisation by mitochondria, activation of the renin–angiotensin–aldosterone system and lipotoxicity. Genetic factors such as microRNAs, long noncoding RNAs and circular RNAs, as well as epigenetic processes such as DNA methylation and histone modifications, also contribute to complications. These factors are potential targets for developing effective new therapies. This review article aims to facilitate in depth understanding of these contributing factors and provide insights into the correlation between diabetes mellitus and cardiovascular complications. Some alternative targets with therapeutic potential are discussed to indicate favourable targets for the management of diabetic cardiomyopathy.

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.