Glutathione-Related Antioxidant Defense System in Elderly Patients Treated for HypertensionRybka, J.; Kupczyk, D.; Kędziora-Kornatowska, K.; Motyl, J.; Czuczejko, J.; Szewczyk-Golec, K.; Kozakiewicz, M.; Pawluk, H.; Carvalho, L.; Kędziora, J.
doi: 10.1007/s12012-010-9096-5pmid: 21140238
The purpose of this study was to analyze glutathione antioxidant defense system in elderly patients treated for hypertension. Studies were carried out in the blood collected from 18 hypertensive and 15 age- and sex-matched controls, all subjects age over 60. Hypertensives were on their usual antihypertensive treatment at the time of blood collection. The concentration of glutathione (GSH) in whole blood and activities of glutathione peroxidase (GPx-1), glutathione transferase (GST), and glutathione reductase (GR) in erythrocytes were measured. The data from patients and controls were compared using independent-samples t test. P value of 0.05 and less was considered statistically significant. We observed increased glutathione-related antioxidant defense in treated hypertensive elderly patients (HT) when compared with healthy controls (C). Mean GSH concentration was significantly higher in HT when compared with C: 3.1 ± 0.29 and 2.6 ± 0.25 mmol/L, respectively, P < 0.001. Mean activity of GR was significantly higher in HT group if compared with C: 83.4 ± 15.25 U/g Hb versus 64.2 ± 8.26 U/g Hb, respectively, P < 0.001. Mean activity of GST was significantly higher in HT group compared with C: 3.0 ± 0.60 mmol CDNB-GSH/mgHb/min and 2.6 ± 0.36 mmol CDNB-GSH/mgHb/min, respectively, P < 0.05. No difference in GPx activity was observed between two groups. These results show that glutathione-related antioxidant defense system was enhanced in elderly hypertensive patients treated for their conditions. This suggests important role of glutathione system in blood pressure regulation. Alterations in concentration and activity of antioxidants observed during antihypertensive medication are likely to be related to the effect of the treatment on NO bioavailability.
Protective Effect of FK506 on Myocardial Ischemia/Reperfusion Injury by Suppression of CaN and ASK1 Signaling CircuitryFeng, Xing; Li, Jing; Liu, Jinyu; Jin, Minghua; Liu, Xiaomei; Du, Haiying; Zhang, Long; Sun, Zhiwei; Li, Xiaoguang
doi: 10.1007/s12012-010-9095-6pmid: 21076890
We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.
Gene Expression, Function and Ischemia Tolerance in Male and Female Rat Hearts After Sub-Toxic Levels of Angiotensin IIAljabri, M.; Lund, T.; Höper, A.; Andreasen, T.; Al-Saad, S.; Lindal, S.; Ytrehus, K.
doi: 10.1007/s12012-010-9100-0pmid: 21170686
To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter–matched rats were treated with 400 ng kg−1 min−1 Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, β-MCH, Ankrd-1, PKC-α, PKC-δ TNF-α); fibrosis (Col I-α1, Col III-α1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response.
Mechanistic Clues in the Cardioprotective Effect of Terminalia Arjuna Bark Extract in Isoproterenol-Induced Chronic Heart Failure in RatsParveen, Adila; Babbar, Rashmi; Agarwal, Sarita; Kotwani, Anita; Fahim, Mohammad
doi: 10.1007/s12012-010-9099-2pmid: 21116736
The present study demonstrated prophylactic and therapeutic potential of Terminalia arjuna bark extract in isoproterenol (ISO)-induced chronic heart failure (CHF). Fifteen days after injection of ISO (85 mg/kg twice at an interval of 24 h, s.c), rats showed decline in maximal rate of rise and fall of left ventricular pressure (LV (dP/dt)max and LV (dP/dt)min), cardiac contractility index (LV (dP/dt)max/LVP), cardiac output and rise in LV end-diastolic pressure. CHF rats showed a significant increase in serum creatine kinase isoenzyme-MB (CK-MB) and malondialdehyde levels, as well as fall in the activities of superoxide dismutase, reduced glutathione. Altered lipid profile and increased level of cytokine tumour necrosis factor-α (TNF-α) along with histological changes in heart were also observed in CHF rats. T. arjuna bark extract (500 mg/kg, p.o) treatment prior and 15 days after ISO injection significantly attenuated cardiac dysfunction and myocardial injury in CHF rats. Cardioprotective action of T. arjuna was comparable to fluvastatin, a synthetic drug. The results suggest that T. arjuna bark extract has a significant prophylactic and therapeutic beneficial effect on protection of heart against ISO-induced CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.
Preventive Effects of Vanillic Acid on Lipids, Bax, Bcl-2 and Myocardial Infarct Size on Isoproterenol-Induced Myocardial Infarcted Rats: A Biochemical and In Vitro Study Prince, P.; Dhanasekar, K.; Rajakumar, S.
doi: 10.1007/s12012-010-9098-3pmid: 21161433
We made an attempt to evaluate the preventive effects of vanillic acid on isoproterenol-induced myocardial infarcted rats. Rats were pretreated with vanillic acid (5 and 10 mg/kg) daily for 10 days. After pretreatment, rats were injected with isoproterenol (100 mg/kg) at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol induction increased the activity of serum creatine kinase-MB and increased the levels of serum and heart cholesterol, triglycerides, free fatty acids in rats. It increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high-density lipoprotein cholesterol. Also, the activity of 3-hydroxy-3methyl glutaryl-coenzyme-A-reductase in the plasma and liver was increased, and lecithin cholesterol acyl transferase activity in the plasma and liver was decreased in isoproterenol-induced rats. Furthermore, isoproterenol-induced rats showed a decrease in myocardial expression of B-cell leukemia/lymphoma-2(bcl-2) gene and an increase in myocardial expression of bcl-2 associated-x (bax)-gene. Vanillic acid pretreated isoproterenol-induced rats positively altered all the above-mentioned biochemical parameters. Vanillic acid pretreatment also reduced myocardial infarct size in myocardial infarcted rats. In vitro study confirmed the potent free radical scavenging effect of vanillic acid. The observed effects are due to free radical scavenging effects of vanillic acid. This study may have a significant impact on myocardial infarcted patients.
Homocysteine Induces Oxidative–Nitrative Stress in Heart of Rats: Prevention by Folic AcidKolling, Janaína; Scherer, Emilene; Cunha, Aline; Cunha, Maira; Wyse, Angela
doi: 10.1007/s12012-010-9094-7pmid: 21076891
Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and thrombosis; however, the mechanisms by which homocysteine triggers these dysfunctions are not fully understood. In the present study, we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely thiobarbituric acid reactive substances, an index of lipid peroxidation, 2′,7′-dichlorofluorescein (H2DCF) oxidation, activities of antioxidant enzymes named superoxide dismutase and catalase, as well as nitrite levels in heart of young rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3–0.6 μmol/g body weight) and/or folic acid (0.011 μmol/g body weight) from their 6th to the 28th day of life. Controls and treated rats were killed 1 h and/or 12 h after the last injection. Results showed that chronic homocysteine administration increases lipid peroxidation and reactive species production and decreases enzymatic antioxidant defenses and nitrite levels in the heart of young rats killed 1 h, but not 12 h after the last injection of homocysteine. Folic acid concurrent administration prevented homocysteine effects probable by its antioxidant properties. Our data indicate that oxidative stress is elicited by chronic hyperhomocystenemia, a mechanism that may contribute, at least in part, to the cardiovascular alterations characteristic of hyperhomocysteinemic patients. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in cardiovascular alterations caused by homocysteine.
A Combination of Melatonin and Alpha Lipoic Acid has Greater Cardioprotective Effect than Either of them Singly Against Cadmium-Induced Oxidative DamageMukherjee, Raktim; Banerjee, Sudeep; Joshi, Niraj; Singh, Prem; Baxi, Darshee; Ramachandran, A.
doi: 10.1007/s12012-010-9092-9pmid: 21046280
Present study evaluates cardioprotective role of melatonin (Mel), alpha lipoic acid (ALA), a combination of melatonin and alpha lipoic acid (Mel + ALA) against cadmium (Cd)-induced oxidative damage. Female albino rats were subjected to 15-day exposure to Cd (5.12 mg/kg bw) alone or treated with ML (10 mg/kg bw) + ALA (25 mg/kg bw) simultaneously. Plasma markers of cardiac damage, cardiac free radical generation, lipid peroxidation, endogenous antioxidant status, cadmium load, metallothionein induction, and histopathology were evaluated in various experimental groups. Combination of Mel + ALA significantly prevented leakage of marker enzymes of cardiac damage, changes in cardiac free radical generation, endogenous antioxidants, antioxidant status, structural alterations and augmented the degree of metallothionein (MT) induction. The results demonstrate that ML + ALA co-administration effectively protected against Cd-induced cardiac oxidative damage.