Vitamin D Protects Against Cardiac Hypertrophy Through the Regulation of Mitochondrial Function in Aging Rats.

Cardiac aging is defined as mitochondrial dysfunction of the heart. Vitamin D (VitD) is an effective agent in ameliorating cardiovascular disorders. In this study, we indicated the protective effects of VitD against cardiac aging. Male Wistar rats were randomly divided into four groups: control (CONT), D-galactose (D-GAL): aged rats induced by D-GAL, D-GAL + Ethanol: aged rats treated with ethanol, and D-GAL + VitD aged rats treated with VitD. Aging was induced by D-GAL at 150 mg/kg via intraperitoneal injection for 8 weeks. Aged rats were treated with VitD (D-GAL + VitD) by gavage for 8 weeks. The serum samples were used to evaluate biochemical factors, and heart tissues were assessed to determine oxidative stress and gene expression. The D-GAL rats exhibited cardiac hypertrophy, which was associated with decreased antioxidant enzyme activity, enhanced oxidative marker, and changes in the expression of mitochondrial genes in comparison with the control rats. Co-treatment with VitD ameliorated all these changes. In conclusion, VitD could protect the heart against D-GAL-induced aging via enhancing antioxidant effects, and the expression of mitochondrial genes.

Effect of diminazene on cardiac hypertrophy through mitophagy in rat models with hyperthyroidism induced by levothyroxine.

Hyperthyroidism is associated with the alteration in molecular pathways involved in the regulation of mitochondrial mass and apoptosis, which contribute to the development of cardiac hypertrophy. Diminazene (DIZE) is an animal anti-infection drug that has shown promising effects on improving cardiovascular disease. The aim of the present study was to investigate the therapeutic effect of DIZE on cardiac hypertrophy and the signaling pathways involved in this process in the hyperthyroid rat model. Twenty male Wistar rats were equally divided into four groups: control, hyperthyroid, DIZE, and hyperthyroid + DIZE. After 28 days of treatment, serum thyroxine (T4) and thyroid stimulating hormone (TSH) level, cardiac hypertrophy indices, cardiac damage markers, cardiac malondialdehyde (MDA), and superoxide dismutase (SOD) level, the mRNA expression level of mitochondrial and apoptotic genes were evaluated. Hyperthyroidism significantly decreased the cardiac expression level of SIRT1/PGC1α and its downstream involved in the regulation of mitochondrial biogenesis, mitophagy, and antioxidant enzyme activities including TFAM, PINK1/MFN2, Drp1, and Nrf2, respectively, as well as stimulated mitochondrial-dependent apoptosis by reducing Bcl-2 expression and increasing Bax expression. Treatment with DIZE significantly reversed the downregulation of SIRT1, PGC1α, PINK1, MFN2, Drp1, and Nrf2 but did not significantly change the TFAM expression. Moreover, DIZE suppressed apoptosis by normalizing the cardiac expression levels of Bax and Bcl-2. DIZE is effective in attenuating hyperthyroidism-induced cardiac hypertrophy by modulating the mitophagy-related pathway, suppressing apoptosis and oxidative stress.

Cardioprotective effect of naringin against the ischemia/reperfusion injury of aged rats.

Aging is known as a main risk factor in the development of cardiovascular diseases. Naringin (NRG) is a flavonoid compound derived from citrus fruits. It possesses a wide spectrum of pharmacological properties, including antioxidant anti-inflammatory, and cardioprotective. This investigation aimed to assess the cardioprotective effect of NRG against the ischemia/reperfusion (I/R) injury in aged rats. In this study, D-galactose (D-GAL) at the dose of 150 mg/kg/day for 8 weeks was used to induce aging in rats. Rats were orally gavaged with NRG (40 or 100 mg/kg/day), in co-treatment with D-GAL, for 8 weeks. The Langendorff isolated heart was used to evaluate the effect of NRG on I/R injury in aged rats. NRG treatment diminished myocardial hypertrophy and maximum contracture level in aged animals. During the pre-ischemic phase, reduced heart rate was normalized by NRG. The effects of D-GAL on the left ventricular end diastolic pressure (LVDP), the rate pressure product (RPP), and the minimum and maximum rate of left ventricular pressure (±dp/dt) improved by NRG treatment in the perfusion period. NRG also enhanced post-ischemic recovery of cardiac functional parameters (± dp/dt, and RPP) in isolated hearts. An increase in serum levels of the lactate dehydrogenase (LDH), the creatine kinase-MB (CK-MB), and the tumor necrosis factor-alpha (TNF-α) were reversed by NRG in aged rats. It also normalized the D-GAL-decreased the superoxide dismutase (SOD) activity in the heart tissue. NRG treatment alleviated cardiac injury in aged hearts under conditions of I/R. NRG may improve aging-induced cardiac dysfunction through anti-oxidative and anti-inflammatory mechanisms.

Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy.

BACKGROUND: Cardiac apoptosis plays a key role in increased morbidity associated with aging-induced-cardiac disorder. Mitochondria play an important role in cardiac apoptosis, and dynamin-related protein 1 (Drp1), as a main mediator of mitochondrial fission, can trigger the mitophagy process to sustain the mitochondrial quality. The present study was done to determine the effect of vitamin D (VitD) treatment on cardiac hypertrophy through mitophagy regulation in aged animals induced by D-galactose (D-GAL). METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups: control, D-GAL (aging group), D-GAL co-injected with VitD (D-GAL ± VitD), and D-GAL plus ethanol (D-GAL ± Ethanol). Aging was induced by an intraperitoneal (i.p.) administration of D-GAL at 150 mg/kg daily for eight weeks and also VitD (400 IU/kg) or ethanol was injected (i.p.) into aging rats. Then, the levels of cardiac mitophagy and cardiac apoptosis were determined by measuring the expression of tensin homologue (PTEN)-induced putative kinase 1 (PINK1), Drp1, Bcl2-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes. Aging in rats was associated with a reduction in mitophagy and also an increase in apoptosis of the heart through down-regulation of Drp1, PINK1, and Bcl2 genes and also up-regulation of Bax. However, VitD improved cardiac hypertrophy through cardiac mitophagy in D-GAL-induced aging rats. CONCLUSION: VitD can inhibit cardiac hypertrophy by an increase in mitophagy and a decrease in apoptosis in the aging heart. The illustration of the suggested mechanism underlying of Vitamin D in cardiac hypertrophy induced by aging.

Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging.

BACKGROUND: Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats. METHODS AND RESULTS: Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels. CONCLUSIONS: GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.

Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a tissue damage during reperfusion after an ischemic condition. I/R injury is induced by pathological cases including stroke, myocardial infarction, circulatory arrest, sickle cell disease, acute kidney injury, trauma, and sleep apnea. It can lead to increased morbidity and mortality in the context of these processes. Mitochondrial dysfunction is one of the hallmarks of I/R insult, which is induced via reactive oxygen species (ROS) production, apoptosis, and autophagy. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play a main regulatory role in gene expression. Recently, there are evidence, which miRNAs are the major modulators of cardiovascular diseases, especially myocardial I/R injury. Cardiovascular miRNAs, specifically miR-21, and probably miR-24 and miR-126 have protective effects on myocardial I/R injury. Trimetazidine (TMZ) is a new class of metabolic agents with an anti-ischemic activity. It has beneficial effects on chronic stable angina by suppressing mitochondrial permeability transition pore (mPTP) opening. The present review study addressed the different mechanistic effects of TMZ on cardiac I/R injury. Online databases including Scopus, PubMed, Web of Science, and Cochrane library were assessed for published studies between 1986 and 2021. TMZ, an antioxidant and metabolic agent, prevents the cardiac reperfusion injury by regulating AMP-activated protein kinase (AMPK), cystathionine-γ-lyase enzyme (CSE)/hydrogen sulfide (H2S), and miR-21. Therefore, TMZ protects the heart against I/R injury by inducing key regulators such as AMPK, CSE/H2S, and miR-21.

Neuroprotective effect of geraniol on neurological disorders: a review article.

BACKGROUND: Neurological disorders are structural, biochemical, and electrical abnormalities that affect the peripheral and central nervous systems. Paralysis, muscle weakness, tremors, spasms, and partial or complete loss of sensation are some symptoms of these disorders. Neurorehabilitation is the main treatment for neurological disorders. Treatments can improve the quality of life of patients. Neuroprotective substances of natural origin are used for the treatments of these disorders. METHODS AND RESULTS: Online databases, such as Google Scholar, PubMed, ScienceDirect, and Scopus were searched to evaluate articles from 1981-2021 using the Mesh words of geraniol (GER), neurological disorders, epilepsy, spinal cord injury (SCI), Parkinson's diseases (PD), and depression. A total of 87 studies were included in this review. GER with antioxidant, anti-inflammatory, and neuroprotective effects can improve the symptoms and reduce the progression of neurological diseases. GER exhibits neuroprotective effects by binding to GABA and glycine receptors as well as by inhibiting the activation of nuclear factor kappa B (NF-κB) pathway and regulating the expression of nucleotide-binding oligomerization of NLRP3 inflammasome. In this study, the effect of GER was investigated on neurological disorders, such as epilepsy, SCI, PD, and depression. CONCLUSION: Although the medicinal uses of GER have been reported, more clinical and experimental studies are needed to investigate the effect of using traditional medicine on improving lifethreatening diseases and the quality of life of patients.

Gallic acid protects against isoproterenol-induced cardiotoxicity in rats.

BACKGROUND: Gallic acid (GA) is a polyphenolic agent with interesting pharmacological impacts on the cardiovascular system. OBJECTIVE: The present study purposed to study the protective effects of GA at 25 and 50 mg/kg against isoproterenol (ISO)-induced cardiac damage in ischemia/reperfusion (I/R) in rats. METHODS: Male Wistar rats were randomly assigned into six groups: Control, Control treated with GA at 25 mg/kg (GA25), Control treated with GA at 50 mg/kg (GA50), Hypertrophic rats induced by ISO (ISO), Hypertrophic rats treated with GA at 25 mg/kg (ISO+GA25), and Hypertrophic rats treated with GA at 50 mg/kg (ISO+GA50). Heart isolation was performed to induce a cardiac I/R injury model. Cardiac hemodynamic parameters were recorded. Serum Lactate Dehydrogenase (LDH) and Creatine Kinase-MB (CK-MB) and cardiac Superoxide dismutases (SOD) levels were evaluated. The gene expression of Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) was assessed. RESULTS: We found that GA at 50 mg/kg was significantly increased cardiac function at post I/R period in ISO-induced hypertrophic hearts. Moreover, it suppressed cardiac hypertrophy, the serum LDH and CK-MB levels in ISO injected rats. Administration of GA at 50 mg/kg was significantly increased SOD level and SERCA2a gene expression in the hypertrophic hearts. CONCLUSION: GA at 50 mg/kg could improve cardiac performance possibly by increasing antioxidant defense enzymes, reducing cell damage, and enhancing SERCA2a gene expression in hypertrophic heart induced by ISO in I/R injury conditions.

The antidiabetic and hepatoprotective effects of myricitrin on aged mice with D-galactose.

AIM: The present study aims to evaluate the effects of antidiabetic and hepatoprotective of myricitrin in the aged mice induced by D-galactose (D-gal). BACKGROUND: Aging occurs during a person's life; there has been no way to stop the aging process, but antioxidant and changing lifestyles can delay it. METHODS: In this experimental study, 72 female adult mice (weighing30-35g) were randomly divided into six groups: 1: control, 2: D-gal at 500mg/kg/d, 3-5: D-gal+ Myricitrin at 5, 10 and 20mg/kg/d 6: D-gal+ Vitamin E at 100mg/kg/d. Aging induced by D-gal for 45 days via intraperitoneal. Myricitrin and Vitamin E administrated orally by gavage for the last 28 days. The blood glucose, insulin level, ß-cell function, insulin resistance, hepatic enzymes, lipid profile, and histology of the liver, and pancreas were evaluated. RESULTS: D-gal injection increased the glucose (p<0.001) and insulin levels (p<0.01) compared to control group. Myricitrin (p<0.01) and Vitamin E (p<0.001) increased insulin and decreased blood glucose levels compared to D-gal group. Myricitrin had a similar impact on insulin levels to vitamin E. Insulin resistance induced in the D-gal group (p<0.001). Myricitrin reduced insulin resistance and increased ß-cell function (p<0.01) compared to D-gal group. D-gal elevated (p<0.01) cholesterol, LDL and triglyceride level, myricitrin (p<0.001), and Vitamin E (p<0.05) were reduced. CONCLUSION: D-gal-induced aging causes the accumulation of RBCs, inflammation in the liver, and changes in the number and diameter of Langerhans islets in the pancreas. Myricitrin improved these D-gal effects. Myricitrin had the anti-diabetic and hepatoprotective effects on the aged mice induced by D-galactose.

Trimetazidine Increases Plasma MicroRNA-24 and MicroRNA-126 Levels and Improves Dyslipidemia, Inflammation and Hypotension in Diabetic Rats.

Trimetazidine (TMZ) improves endothelial dysfunction. However, its beneficial effect on endothelial miRNAs is unexplored in diabetes. The aim of the present study was to evaluate the effects of TMZ on plasma miRNA-24 and miRNA-126, dyslipidemia, inflammation, and blood pressure in the diabetic rats. Adult male Sprague-Dawley rats were randomly assigned into four groups (250 ± 20 g, n = 8): a control (C), an untreated diabetic (D), a diabetic group administrated with TMZ at 10 mg/kg (T10), and a diabetic group administrated with TMZ at 30 mg/kg (T30) for eight weeks. Diabetes was induced by injection of alloxan (120 mg/kg). The plasma levels of miR-24, miR-126, lipid profile, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), blood glucose, body weight and systolic blood pressure were measured. The diabetic rats showed decreased plasma miR-24, HDL-c (P < 0.05), miR-126 (P < 0.01), body weight changes percent, body weight, and systolic blood pressure (P < 0.001) and increased triglycerides (TG), VLDL-c (P < 0.05), TNF-α, total cholesterol (TC) (P < 0.01) glucose, MDA and IL-6 (P < 0.001). Interestingly, all these changes were significantly improved by TMZ treatment. Our findings propose that TMZ has protective effects on decreased plasma miR-24 and miR-126 levels, inflammation, dyslipidemia and hypotension, and it may participate in endothelial dysfunction and atherosclerosis.

Protective effects of gallic acid on cardiac electrophysiology and arrhythmias during reperfusion in diabetes.

OBJECTIVES: Gallic acid (GA), a potent anti-oxidant, plays an important role in reducing diabetic induced cardiac disorders. Therefore, the present investigation was purposed to determine the beneficial effect of GA in cardiac arrhythmias during reperfusion in diabetes induced by alloxan. MATERIALS AND METHODS: Male Sprague-Dawley rats (200-250 g) were randomly divided into three groups (eight in each group): control (C), diabetic (D), and diabetic treated with GA (D+G) groups. GA was administered by gavage (25 mg/kg, daily) for eight weeks. Diabetes was induced by a single intraperitoneal injection of alloxan (120 mg/kg). Ischemia-reperfusion (IR) injury was performed by ischemia and then reperfusion (30 and 120 min, respectively). The score and magnitude of arrhythmias, creatine kinase (CK-MB), and lactate dehydrogenase (LDH) of the heart, electrocardiographic, and hemodynamic parameters were measured. One-way ANOVA followed by LSD tests were used for the differences between groups. The percentage of incidence was also evaluated by Fisher's exact test. RESULTS: The duration (P<0.05), onset (P<0.01), score and incidence of arrhythmia, QT interval (P<0.001), LDH, and CK-MB (P<0.05) were significantly elevated and the contractility of the heart (±dp/dt, P<0.01), LVSP, QRS complex voltage (P<0.05), and heart rate (P<0.01) were significantly reduced in the diabetic animals compared with the control rats. However, administration with GA significantly improved these alterations in the diabetic group compared with the diabetic animals. CONCLUSION: This study indicated the beneficial effects of GA on cardiac electrophysiology and arrhythmias during reperfusion in diabetes.

The Effects of Trimetazidine on QT-interval Prolongation and Cardiac Hypertrophy in Diabetic Rats / Os Efeitos da Trimetazidina no Prolongamento do Intervalo QT e na Hipertrofia Cardíaca em Ratos Diabéticos

Abstract Background: Trimetazidine (TMZ) is an anti-ischemic drug. In spite of its protective effects on cardiovascular system, there is no scientific study on the usefulness of TMZ treatment for prolonged QT interval and cardiac hypertrophy induced by diabetes. Objectives: To evaluate the effects of TMZ on QT interval prolongation and cardiac hypertrophy in the diabetic rats. Methods: Twenty-four male Sprague-Dawley rats (200-250 g) were randomly assigned into three groups (n = 8) by simple random sampling method. Control (C), diabetic (D), and diabetic administrated with TMZ at 10 mg/kg (T10). TMZ was administrated for 8 weeks. The echocardiogram was recorded before isolating the hearts and transfer to a Langendorff apparatus. Hemodynamic parameters, QT and corrected QT interval (QTc) intervals, heart rate and antioxidant enzymes were measured. The hypertrophy index was calculated. The results were evaluated by one-way ANOVA and paired t-test using SPSS (version 16) and p < 0.05 was regarded as significant. Results: The diabetic rats significantly indicated increased hypertrophy, QT and QTc intervals and decreased Left ventricular systolic pressure (LVSP), Left ventricular developed pressure (LVDP), rate pressure product (RPP), Max dp/dt, and min dp/dt (±dp/dt max), heart rate, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in the heart. Treatment with TMZ in the diabetic animals was significantly improved these parameters in comparison to the untreated diabetic group. Conclusions: TMZ improves QTc interval prolongation and cardiac hypertrophy in diabetes.

Resumo Fundamento: A trimetazidina (TMZ) é uma droga anti-isquêmica. Apesar de seus efeitos protetores sobre o sistema cardiovascular, não há estudos científicos sobre a utilidade do tratamento com TMZ para o intervalo QT prolongado e a hipertrofia cardíaca induzida pelo diabetes. Objetivo: Avaliar os efeitos da TMZ no prolongamento do intervalo QT e na hipertrofia cardíaca em ratos diabéticos. Métodos: Vinte e quatro ratos machos Sprague-Dawley (200-250 g) foram distribuídos aleatoriamente em três grupos (n = 8) pelo método de amostragem aleatória simples. Controle (C), diabético (D) e diabético administrado com TMZ a 10 mg/kg (T10). A TMZ foi administrada por 8 semanas. O ecocardiograma foi registrado antes de isolar os corações e transferir para um aparelho de Langendorff. Foram medidos os parâmetros hemodinâmicos, intervalo QT e intervalo QT corrigido (QTc), frequência cardíaca e enzimas antioxidantes. O índice de hipertrofia foi calculado. Os resultados foram avaliados pelo one-way ANOVA e pelo teste t pareado pelo SPSS (versão 16) e p < 0,05 foi considerado significativo. Resultados: Os ratos diabéticos indicaram hipertrofia aumentada, intervalos QT e QTc e diminuição da pressão sistólica no ventrículo esquerdo (PSVE), pressão desenvolvida no ventrículo esquerdo (PDVE), duplo produto (DP), Max dp/dt e min dp/dt (± dp/dt max), frequência cardíaca, superóxido dismutase (SOD), glutationa peroxidase (GPx) e catalase no coração. O tratamento com TMZ nos animais diabéticos melhorou significativamente esses parâmetros em comparação com o grupo diabético não tratado. Conclusões: A TMZ melhora o prolongamento do intervalo QTc e a hipertrofia cardíaca no diabetes.

The Beneficial Effects of Trimetazidine on Reperfusion-Induced Arrhythmia in Diabetic Rats.

Trimetazidine (TMZ), as an anti-ischemic drug, plays a critical role in protecting against cardiovascular complications induced by diabetes. This study was therefore aimed to evaluate the protective effects of TMZ on reperfusion-induced arrhythmias in the diabetic rats. Male Sprague-Dawley rats (250±20 g) were randomly assigned to four (n=8): control rats (C), alloxan induced diabetic rats (D), diabetic rats treated with TMZ (10 mg/kg, D+T10), diabetic rats treated with TMZ (30 mg/kg, D+T30). TMZ was treated orally once daily for 8 weeks. Diabetes was induced by a single intraperitoneal injection of alloxan (120 mg/kg). Ischemia-reperfusion (I/R) was carried out via 30 min of ischemia and following120-min reperfusion. The magnitude and score of arrhythmia, the left ventricular function, infarct size, lactate dehydrogenase (LDH), myocardial creatine kinase (CK-MB) and troponin (cTnI) were measured. The findings were evaluated by two-way repeated measures and one-way ANOVA followed by LSD post hoc test and Fisher's exact test for incidence percentage. The duration, incidence and score of arrhythmia (p<0.001), infarct size (p<0.01) were significantly increased, the cardiac contractility (±dp/dt), LDH, CK-MB (p<0.001) and cTnI (p<0.05) were significantly decreased in the diabetic rats in comparison with the control group. However, treatment with TMZ in the diabetic rats was significantly improved the duration (p<0.001), incidence and score of arrhythmia,±dp/dt LDH, CK-MB, cTnI (p<0.05) and infarct size (p<0.01) in comparison with the untreated diabetic group. The present study indicates anti-arrhythmic effect of TMZ in reducing arrhythmias induced by reperfusion in the diabetic rats.

The Effects of Trimetazidine on QT-interval Prolongation and Cardiac Hypertrophy in Diabetic Rats.

BACKGROUND: Trimetazidine (TMZ) is an anti-ischemic drug. In spite of its protective effects on cardiovascular system, there is no scientific study on the usefulness of TMZ treatment for prolonged QT interval and cardiac hypertrophy induced by diabetes. OBJECTIVES: To evaluate the effects of TMZ on QT interval prolongation and cardiac hypertrophy in the diabetic rats. METHODS: Twenty-four male Sprague-Dawley rats (200-250 g) were randomly assigned into three groups (n = 8) by simple random sampling method. Control (C), diabetic (D), and diabetic administrated with TMZ at 10 mg/kg (T10). TMZ was administrated for 8 weeks. The echocardiogram was recorded before isolating the hearts and transfer to a Langendorff apparatus. Hemodynamic parameters, QT and corrected QT interval (QTc) intervals, heart rate and antioxidant enzymes were measured. The hypertrophy index was calculated. The results were evaluated by one-way ANOVA and paired t-test using SPSS (version 16) and p < 0.05 was regarded as significant. RESULTS: The diabetic rats significantly indicated increased hypertrophy, QT and QTc intervals and decreased Left ventricular systolic pressure (LVSP), Left ventricular developed pressure (LVDP), rate pressure product (RPP), Max dp/dt, and min dp/dt (±dp/dt max), heart rate, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in the heart. Treatment with TMZ in the diabetic animals was significantly improved these parameters in comparison to the untreated diabetic group. CONCLUSIONS: TMZ improves QTc interval prolongation and cardiac hypertrophy in diabetes.

Effects of gallic acid on hemodynamic parameters and infarct size after ischemia-reperfusion in isolated rat hearts with alloxan-induced diabetes.

Diabetic rats are more susceptible to myocardial ischemia-reperfusion injury than control rats. The aim of the present study was to evaluate the cardioprotective effect of gallic acid (GA) on isolated rat hearts with alloxan-induced diabetes mellitus. Adult male Sprague-Dawley rats were divided randomly into three groups: control, untreated diabetic and diabetic animals treated with (GA, 25mg/kg). Diabetes was induced by 120mg/kg alloxan injection. Eight weeks after GA administration, the hearts were isolated and exposed to myocardial ischemia-reperfusion. The body weight, blood glucose, hypertrophy index, left ventricular function, infarct size, cardiac markers and oxidative stress were measured. In the diabetic group, body weight, cardiac contractility (±dp/dt), glutathione peroxidase (GPx) level (p<0.001), left ventricular developed pressure (LVDP), rate pressure product (RPP), superoxide dismutase (SOD) and catalase (CAT) levels (p<0.01) as well as the heart weight (p<0.05) significantly reduced. However, blood glucose, infarct size, hypertrophy index, lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB, p<0.001) and troponin-I (cTnI) levels (p<0.05) significantly increased in the diabetic rats compared with the control group. Nevertheless, administration of GA improved significantly LVDP, ±dp/dt, infarct size, LDH, CK-MB (p<0.001), blood glucose, the heart weight (p<0.01), body weight, RPP, hypertrophy index, antioxidant enzyme and cTnI levels (p<0.05) in the diabetic rats. The results of this study indicated that in the diabetic rats, left ventricular dysfunction and hypertrophy significantly induced possibly by oxidative stress. Moreover, GA as a potent antioxidant improved both left ventricular dysfunction and hypertrophy.