Cardiac Malondialdehyde Research Articles

Effectiveness of Nano Curcumin and Curcumin as Heart Cell Protectors towards Oxidative Stress through Malondialdehyde (MDA) and Superoxide Dismutase (SOD) Level Analysis in Rats (Rattus norvegicus): A Systematic Review

Background: Oxidative stress is a disturbance which is caused by imbalance of reactive oxygen species (ROS) and antioxidants. Heart is one of the main target organs because it is the highest ROS producer. Malondialdehyde (MDA) and superoxide dismutase (SOD) are two biomarkers often used to evaluate oxidative stress. Due to their antioxidant properties, curcumin and nano curcumin are expected to protect heart from cardiotoxicity caused by oxidative stress. Methods: This is a systematic review of experimental studies available in the literature that reported the curcumin and/or nano curcumin and oxidative stress analyzed through the levels of MDA and SOD in heart of rats. Results: There are 8 out of 8 articles that prove a decrease in cardiac MDA levels after curcumin administration. Seven of them gave significant results with p-value <0.05. Meanwhile, one article stated there is no significant p-value, which is 0.187. A significant increase in SOD levels was shown to occur after curcumin administration in 6 of the 6 articles obtained. Not only curcumin, but nano curcumin can also reduce MDA levels and increase SOD levels of heart significantly. In 4 articles that directly compared the two antioxidants, nano curcumin was able to provide more significant results even at lower doses. Conclusion: Both curcumin and nano curcumin are capable to decrease the level of cardiac MDA and increase the level of cardiac SOD. Nano curcumin is a more effective cardioprotector compared to curcumin through MDA and SOD level analysis in rats.

Novel HM12, A Selective Inhibitor of L‐/T‐type Calcium Channels, Averts Doxorubicin Cardiotoxicity in Male Wistar Rats

Doxorubicin is a cytotoxic anthracycline anticancer drug that is limited by its cardiotoxic action. This study sought to investigate the cardiopreventive potential of HM12, a 1,4‐dihydropyridine (DHP) derivative (CCB) against doxorubicin induced cardiotoxicity in male Wistar rats. HM12 was synthesized as a DHP‐based hexahydroquinoline derivative (2‐[(2‐methylacryloyl)oxy]ethyl 4‐(3,5‐dibromo‐2‐hydro[1]xyphenyl)‐2,6,6‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate) according to the modified Hantzsch reaction via condensation reactions under microwave irradiation. HM12 structure was confirmed using infrared, proton, and carbon‐13 nuclear magnetic resonance, and mass spectra. The CCB activity was evaluated using whole‐cell patch‐clamp assays. Further, fourty‐eight adult male Wistar rats were divided into eight groups of 6/group and received distilled water saline; doxorubicin (DOX, 20 mg/kg, i.p.), HM12 lower (HM12LD) or upper (HM12UD) dose (5 or 20 mg/kg, p.o.), nifedipine (NFD, 20 mg/kg), and their combinations. All rats were sacrificed 24 h after the last administration and changes in blood pressure (BP), heart rate (HR), biochemical, oxidative stress indices, and heart histology were assessed. DOX cardiotoxicity produced spontaneous increased (p&lt;0.05) BP (baseline 106.5/84 mmHg (day 1) versus 170/173.5 mm/Hg (59.6/72%, day 6) and 173.5/167 mmHg (98.8/69.1%, day 7) with altered HR (baseline 99 beats per minutes versus 167.5 bpm (69.1%, day 7). Also, DOX‐treated rats showed a significant increase in tumor necrosis factor‐α (TNF‐α), c‐reactive protein (CRP), and lactate dehydrogenase (LDH). This was accompanied by an increase (p&lt;0.05) in cardiac malondialdehyde (MDAc) and decreased reduced glutathione (GSHc) levels, and activities of catalase (CATc) and superoxide dismutase (SODc). However, HM12UD + DOX had changes BP (baseline 106.5/96 mmHg (day 1) versus 181/179.5 mmHg (70.1/87%, day 6) versus 135/127 mmHg (26.8/32.3%, day 7) with HR (baseline 93.5 beats per minutes versus 164.5 bpm (75.9%, day 6) to 127 bpm (35.8%, day 7). Also, HM12UD was effective against IL‐6, CRP, LDH but not TNF‐α. Further, HM12UD significantly reversed DOX‐induced MDAc by elevating antioxidants GSHc levels as well as activities of CATc and SODs in the treated animals. Additionally, HM12UD averted histopathological changes observed in the rat heart due to DOX intoxication. Overall, the present study conferred new evidence on the protective effects CCBs, in particular, HM12 on DOX‐induced cardiotoxicity, oxidative stress, tumor biomarkers, and cardiac histological changes in rats.

Chronic activation of cardiac Atg-5 and pancreatic Atg-7 by intermittent fasting alleviates acute myocardial infarction in old rats

BackgroundAging is associated with cardiovascular and metabolic changes, increasing the susceptibility to acute myocardial infarction (AMI). Intermittent fasting (IF) has a beneficial effect on the age-associated cardiovascular diseases. The present study was planned to investigate the possible protective effect of IF against acute AMI induced by isoproterenol (ISO) in old rats and its possible underlying mechanisms mediated by heart and pancreatic autophagy. Thirty Male Wistar rats were divided into four groups: adult; old; Old-ISO (rats subjected to AMI by ISO) and Old-F-ISO groups (rats were subjected to IF for 4 weeks and AMI by ISO).ResultsIF significantly increased the mRNA expression of cardiac Atg-5 and pancreatic Atg-7 in Old-F-ISO versus old and adult groups. This was associated with a significant decrease in serum troponin-I, serum creatine kinase (CK-MB), cardiac malondialdehyde and cardiac TNF-α, fasting plasma glucose, and HOMA-IR in Old-F-ISO compared to Old-ISO group. Also, IF significantly decreased the age-related overall and visceral obesity in Old-F-ISO versus old and Old-ISO groups. Histological studies revealed attenuation of the local inflammatory response in Old-F-ISO versus Old-ISO group. Pancreatic Atg-7 and heart Atg-5 were significantly increased in Old-ISO versus old rats.ConclusionsIF protects against acute AMI in old rats, possibly, via chronic activation of heart Atg-5 and pancreatic Atg-7, and alleviation of age-related overall and visceral obesity. Thus, IF could be a dietary lifestyle modification for attenuation of the susceptibility to acute AMI in aged population. On the other hand, acute activation of heart and pancreatic autophagy by ISO might augment cardiac injury.

Hydrogen Attenuates Thyroid Hormone-Induced Cardiac Hypertrophy in Rats by regulating angiotensin II type 1 receptor and NADPH oxidase 2 mediated oxidative stress

Cardiac hypertrophy occurs as a result of high levels of thyroid hormone, which may contribute to heart failure and is closely related to oxidative stress. Hydrogen is a good antioxidant. In this study, we found that intragastric levothyroxine administration for two weeks caused obvious cardiac hypertrophy without reduced systolic function. Additionally, hydrogen inhalation ameliorated the levothyroxine-induced metabolic increase and cardiac hypertrophy in rats. Serum brain natriuretic peptide expression was also attenuated by hydrogen treatment. However, hydrogen had no significant effect on levothyroxine -induced serum troponin I and serum thyroid hormone changes.Hydrogen treatment also reduced the levothyroxine-induced increase in cardiac malondialdehyde, 8-hydroxy-2-deoxyguanosine and serum hydrogen peroxide levels and upregulated superoxide dismutase and glutathione peroxidase activity. Additionally, western blotting results showed that hydrogen inhalation inhibited the expression of cardiac nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), angiotensin II type 1 receptor, sarcoplasmic reticulum Ca2+-ATPase (SERCA2), phospho-phospholamban and α-myosin heavy chain proteins. In conclusion, the present study revealed a protective effect of hydrogen on levothyroxine -induced cardiac hypertrophy by regulating angiotensin II type 1 receptors and NOX2-mediated oxidative stress in rats.

Anti-obesity Activity of Rida Herbal Bitters in High Fat Diet-Induced Obese Rats

Background: Obesity therapies still a serious issue worldwide and herbs from medicinal plants have play crucial roles in management of metabolic diseases. This study investigated the anti-obesity effects of Rida herbal bitters in high-fat diet-induced obese rats. Materials and Methods: Thirty two (32) male Wistar rats were used and randomly divided into four (4) groups, 8rats/group. Group I: normal control; Group II: high-fat diet (obese control); Group III &amp; IV: high-fat diet (obese rats), administered with (0.3ml) Rida herbal bitters and (40mg/kgb.w), Simvastatin respectively for 6 weeks. Food intake was assessed daily and body weight weekly. The animals were sacrificed at the end of the experiment and blood samples were collected for biochemical parameters estimations. Results: High-fat diet significantly (p&lt;0.05) increased the body weight, food intake, blood glucose, insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), very-low density lipoprotein-cholesterol (VLDL-C), atherogenic index, cardiac risk index, leptin, creatinine, urea, uric acid, and malondialdehyde (MDA) level and significantly (p&lt;0.05) reduced high-density lipoprotein-cholesterol (HDL-C), ghrelin, adiponectin, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and reduced glutathione (GSH), levels. Treatments with Rida herbal bitters significantly (p&lt;0.05) lowered the body weight, food intake, blood glucose, insulin, TC, TG, LDL-C, VLDL-C, atherogenic index, cardiac risk index, creatinine, uric acid, urea, leptin and MDA level and significantly (p&lt;0.05) elevates HDL-C, ghrelin, adiponectin, SOD, GPx, CAT, and GSH levels. Conclusion: Rida herbal bitters ameliorate the metabolic alterations induced by high-fat diet and may be a promising therapy for obesity and its complications.

Protective Effect of Kaempferol and Its Nanoparticles on 5-Fluorouracil-Induced Cardiotoxicity in Rats.

Background Fluorouracil (5-FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5-FU-associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti-inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5-FU-induced cardiotoxicity in rats. Methods Thirty Male Wistar rats were divided into five groups as follows: control, 5-FU, 5-FU+10 mg/kg vitamin C, 5-FU+ 1 mg/kg KPF, and 5-FU+ 1 mg/kg KPF-NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF-NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. Results 5-FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX-2 (cyclooxygenase-2) expression, and histopathological degenerations. 5-FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF-NPs reduced oxidative stress, cardiac enzymes, COX-2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF-NPs. Conclusion Our results demonstrated that treatment with KPF and KPF-NPs significantly improved cardiotoxicity induced by 5-FU in rats.

Protective Effects of Chrysin against Cyclophosphamide-Induced Cardiotoxicity in Rats: A Biochemical and Histopathological Approach.

Mounting evidences have indicated that cyclophosphamide (CyC)a potent anticancer and cytotoxic agent is associated with various organ and systemic toxicities and the cytotoxic effects observed after administration of CyC still challenges its clinical use. Chrysin (Chy) is a dietary flavonoid with prevailing antioxidant and anti-inflammatory properties. This study evaluated the protective properties of Chy against CyC-induced cardiotoxicity in rats. The animals were orally treated with Chy (25 and 50 mg/kg/day) for 35 days and exposed to CyC (i. p., 100 mg/kg) once a week for four weeks. The results indicated that CyC caused significant cardiotoxicity as manifested by notable increases in heart weight, cardiac function biomarkers such as lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), troponin T and aspartate transaminase (AST). In addition, cardiac malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL1 β) and interleukin 6 (IL-6) levels were considerably increased. Meanwhile, cardiac antioxidant enzymes activities such as superoxide dismutase (SOD) and catalase (CAT), as well as glutathione (GSH) level were suppressed, while H&E stained histopathological assessment showed marked alterations in cardiac tissues. CyC also significantly lowered red blood cells (RBC) and white blood cells (WBC) parameters, whereas treatment with Chy significantly restored the altered biochemical and histopathological features. Conclusively, aforementioned results inferred that Chy offered cardioprotective potentials against CyC-induced cardiotoxicity which may be due to its antioxidant, and anti-inflammatory properties.

Centella asiatica (L.) Urb. Prevents Hypertension and Protects the Heart in Chronic Nitric Oxide Deficiency Rat Model.

Background: Hypertension is a major risk factor for cardiovascular disease (CVD), which is the number one cause of global mortality. The potential use of natural products to alleviate high blood pressure has been demonstrated to exert a cardioprotective effect. Centella asiatica (L.) Urb. belongs to the plant family Apiaceae (Umbelliferae). It contains a high amount of triterpenoid and flavonoid that have antioxidant properties and are involved in the renin-angiotensin-aldosterone system which is an important hormonal system for blood pressure regulation. Objective: This study aimed to investigate the effects of C. asiatica ethanolic extract on blood pressure and heart in a hypertensive rat model, which was induced using oral N(G)-nitro-l-arginine methyl ester (l-NAME). Methods: Male Sprague-Dawley rats were divided into five groups and were given different treatments for 8 weeks. Group 1 only received deionized water. Groups 2, 4, and 5 were given l-NAME (40 mg/kg, orally). Groups 4 and 5 concurrently received C. asiatica extract (500 mg/kg, orally) and captopril (5 mg/kg, orally), respectively. Group 3 only received C. asiatica extract (500 mg/kg body weight, orally). Systolic blood pressure (SBP) was measured at weeks 0, 4, and 8, while serum nitric oxide (NO) was measured at weeks 0 and 8. At necropsy, cardiac and aortic malondialdehyde (MDA) contents, cardiac angiotensin-converting enzyme (ACE) activity, and serum level of brain natriuretic peptide (BNP) were measured. Results: After 8 weeks, the administrations of C. asiatica extract and captopril showed significant (p < 0.05) effects on preventing the elevation of SBP, reducing the serum nitric oxide level, as well as increasing the cardiac and aortic MDA content, cardiac ACE activity, and serum brain natriuretic peptide level. Conclusion: C. asiatica extract can prevent the development of hypertension and cardiac damage induced by l-NAME, and these effects were comparable to captopril.

Abstract 9380: Rescuing Mitochondrial Fusion/Fission Balance Mitigates Oxidative Stress, Myocardial Injury and Apoptosis in Rats with Doxorubicin-induced Cardiotoxicity

Introduction: Doxorubicin (DOX) has been an extensively used chemotherapeutic drug in handling a wide range of cancers. Cardiotoxicity induced by DOX is a serious adverse effect of oncologic therapy. Although mitochondrial dynamic modulators including mitochondrial fission inhibitor (Mdivi-1) and fusion promoter (M1) have been shown as potential therapeutic remedies to treat various cardiovascular disorders, the cardioprotective effects of Mdivi-1 and M1 in DOX-induced cardiotoxicity is not known. Hypothesis: Mdivi-1 and M1 treatments reduce oxidative stress, myocardial injury, and programmed cell death by apoptosis, leading to improved left ventricular (LV) function in rats with DOX-induced cardiotoxicity. Methods: Male Wistar rats (n=20) were injected with either DOX (3 mg/kg, 6 doses, n=5) or 3% DMSO in NSS (n=5) as a control. In the DOX group, DOX-treated rats were received one of the following treatments: 1) 3% DMSO in NSS (n=5), 2) Mdivi-1 (1.2 mg/kg/day, n=5), 3) M1 (2 mg/kg/day, n=5). All treatments were given to the rats via intraperitoneal injection for 30 days beginning simultaneously with the first DOX injection. LV function, cardiac tissue malondialdehyde (MDA), serum cardiac troponin-I (c-TnI), and cleaved caspase-3 (CC3) protein levels were determined. Results: Injection of DOX markedly increased cardiac MDA, c-TnI, and CC3 levels (Fig. 1A-D). Impaired left ventricular ejection fraction (67% for DOX vs. 91% for control) was observed. Mdivi-1 and M1 co-treatment remarkably reduced the levels of MDA, c-TnI, and CC3, leading to increased LVEF from 67% in DOX to 89% in Mdivi-1 and 90% in M1, respectively (Fig. 1A-D). Conclusions: Mitochondrial fission inhibitor and fusion promoter effectively protected the heart from DOX-induced cardiotoxicity through suppression of oxidative stress, myocardial injury, and apoptosis. These findings indicate the mitochondrial dynamics as novel therapeutic targets in preventing Dox-induced cardiotoxicity.

High-Fat and Combined High-Fat and Sucrose Diets Promote Cardiac Oxidative Stress Independent of Nox2 Redox Regulation and Obesity in Rats.

Oxidative stress is associated with cardiometabolic alterations, and the involvement of excess glucose and fatty acids has been demonstrated in this process. Thus, the aim of this study was to investigate the effects of different hypercaloric diets on cardiac oxidative stress. Wistar rats were randomized into four groups: control (C), high-sucrose (HS), high-fat (HF), and high-fat with sucrose (HFS). Nutritional assessment, food profiles, histological analysis, comorbidities, and cardiovascular characteristics were determined. Cardiac oxidative stress was analyzed by malondialdehyde (MDA) and carbonylated proteins, and the cardiac protein expression levels of type 1 angiotensin receptor (AT-1), nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2), superoxide dismutase (SOD 1 e 2), glutathione peroxidase (GPX), and catalase (CAT) were determined by western blot. The HF group showed an increase in adiposity; however, it did not present adipocyte hypertrophy and comorbidities. Cardiac MDA and carbonylated protein levels were higher in the HF and HFS compared with the C group. The levels of oxidant and antioxidant proteins showed no difference between the groups. HF and HFS dietary interventions promoted cardiac oxidative stress, in the presence and absence of obesity, respectively. However, this process was neither mediated by the pro-oxidants AT1 and Nox2, nor by the quantitative reduction of antioxidant enzymes.

Inhibition of myeloid differentiation factor 2 by MAC28 suppresses reactive oxygen species, inflammation and improves mitochondrial function, leading to improved cardiac function in prediabetic rats

Abstract Background Chronic inflammation involves in the left ventricular (LV) dysfunction in high-fat diet (HFD)-induced prediabetes, along with cardiac mitochondrial dysfunction. This involved an activation of myeloid differentiation factor 2 (MD2)/toll-like receptor 4 (TLR4) by lipopolysaccharide, leading to inflammatory cytokines production in the heart. MAC28 is a novel MD2 inhibitor, which had been shown to provide effects against LPS-induced cytokine secretion from macrophages. However, the potential benefits of MAC28 on the LV function and its underlying mechanisms in HFD-induced prediabetic rats are unknown. Purpose We tested the hypothesis that MAC28 improves LV function in prediabetic rats by reducing cardiac oxidative stress, inflammation, and cardiac mitochondrial dysfunction. Methods Male Wistar rats were fed either a normal diet (ND, n=8) or HFD (n=24) for 16 weeks. At week 12, HFD-fed rats developed prediabetes and LV dysfunction. At this time, these HFD-fed rats were divided into 3 treatment groups (n=8/group): 1) vehicle (HFDV; 1% Na-carboxymethyl cellulose; p.o.); 2) MAC28 (40 mg/kg; p.o.); 3) metformin (300 mg/kg; p.o.; a positive control), the ND-fed rats received a vehicle (NDV). Rats were received their treatment for 4 weeks. Then, LV function and heart rate variability (HRV) were examined, and the heart was removed to determinecardiac malondialdehyde (MDA), cardiac inflammation (TNF-α) and mitochondrial function. Results HFD-induced prediabetes, together with depressed HRV and %LV ejection fraction (LVEF) (Fig. 1A). Moreover, cardiac oxidative stress and inflammation overproduction, and cardiac mitochondrial dysfunction was also observed, shown by elevated cardiac MDA, cardiac TNF-α protein levels, and mitochondrial ROS levels, mitochondrial depolarization and swelling (Fig. 1B). Notably, treatment with MAC28 effectively improved HRV and %LVEF and HRV (Fig. 1A), compared to HFDV group. Moreover, MAC28 significantly reduced cardiac MDA levels, cardiac TNF-α protein levels and cardiac mitochondrial dysfunction in HFD-induced prediabetic rats (Fig. 1B). These beneficial effects were also observed in metformin-treated rats (Fig. 1A, B). Conclusion MAC28 exerts cardioprotection in prediabetic rats by reducing cardiac oxidative stress, inflammation, and mitochondrial dysfunction, leading to restoring LV function. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Thailand Science Research and Innovation

Remote Ischemic Preconditioning Reduces Marathon-Induced Oxidative Stress and Decreases Liver and Heart Injury Markers in the Serum.

Clinical studies continue to provide evidence of organ protection by remote ischemic preconditioning (RIPC). However, there is lack of insight into impact of RIPC on exercise-induce changes in human organs’ function. We here aimed to elucidate the effects of 10-day RIPC training on marathon-induced changes in the levels of serum markers of oxidative stress, and liver and heart damage. The study involved 18 male amateur runners taking part in a marathon. RIPC training was performed in the course of four cycles, by inflating and deflating a blood pressure cuff at 5-min intervals (RIPC group, n=10); the control group underwent sham training (n=8). The effects of RIPC on levels of oxidative stress, and liver and heart damage markers were investigated at rest after 10 consecutive days of training and after the marathon run. The 10-day RIPC training decreased the serum resting levels of C-reactive protein (CRP), alanine transaminase (ALT), γ-glutamyl transpeptidase (GGT), and malondialdehyde (MDA). After the marathon run, creatinine kinase MB (CK-MB), lactate dehydrogenase (LDH), cardiac troponin level (cTn), aspartate aminotransferase (AST), alkaline phosphatase (ALP), ALT, total bilirubin (BIL-T), and MDA levels were increased and arterial ketone body ratio (AKBR) levels were decreased in all participants. The changes were significantly diminished in the RIPC group compared with the control group. The GGT activity remained constant in the RIPC group but significantly increased in the control group after the marathon run. In conclusion, the study provides evidence for a protective effect of RIPC against liver and heart damage induced by strenuous exercise, such as the marathon.

Visnagin prevents isoproterenol-induced myocardial injury by attenuating oxidative stress and inflammation and upregulating Nrf2 signaling in rats.

Oxidative tissue injury and inflammatory responses play major roles in cardiovascular diseases and heart failure. Visnagin (VIS) is a natural bioactive component of Ammi visnaga, with promising radical scavenging and anti-inflammatory activities. This study explored the protective effect of VIS against isoproterenol (ISO)-induced acute myocardial injury and oxidative stress in rats. VIS was supplemented for 14 days, and the rats received ISO (100 mg/kg) twice at an interval of 24 h. ISO-induced myocardial injury was characterized by elevated serum CK-MB, LDH, and troponin-I associated with increased heart weightand several histopathological changes. ISO increased reactive oxygen species (ROS), malondialdehyde (MDA), NF-κB p65, TNF-α, IL-6, and decreased glutathione and antioxidant enzymes in rats' hearts. VIS prevented myocardial injury and ameliorated the cardiac function markers, ROS, MDA, NF-κB p65, and pro-inflammatory cytokines in ISO-intoxicated rats. In addition, VIS decreased Bax mRNA and caspases, and upregulated Nrf2, HO-1, Bcl-2, and PPARγ. Molecular docking simulations revealed the binding method of VIS to NF-κB, Keap1, and PPARγ. In conclusion, VIS protects against ISO-induced acute myocardial injury by attenuating oxidative tissue injury and reducing key inflammatory and apoptosis markers. In vivo and in silico results showed that activation of Nrf2/HO-1 signaling and PPARγ mediates the cardioprotective effect of VIS.

Nano-Curcumin Prevents Cardiac Injury, Oxidative Stress and Inflammation, and Modulates TLR4/NF-κB and MAPK Signaling in Copper Sulfate-Intoxicated Rats.

Copper (Cu) is essential for a plethora of biological processes; however, its high redox reactivity renders it potentially toxic. This study investigated the protective effect of curcumin (CUR) and nano-CUR (N-CUR) against Cu cardiotoxicity, emphasizing the role of oxidative stress, TLR4/NF-κB and mitogen-activated protein kinase (MAPK) signaling and cell death in rats. Rats received 100 mg/kg copper sulfate (CuSO4), a pesticide used for repelling pests, and were concurrently treated with CUR or N-CUR for 7 days. Cu caused cardiac injury manifested by elevated serum cardiac troponin I (cTnI), creatine kinase (CK)-MB, and lactate dehydrogenase (LDH), as well as histopathological alterations. Cardiac malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 were increased, and reduced glutathione (GSH), superoxide dismutase (SOD) and catalase were decreased in Cu-treated rats. CUR and N-CUR prevented cardiac tissue injury, decreased serum cTnI, CK-MB, and LDH, and cardiac MDA, NF-κB p65, TNF-α, and IL-6, and enhanced cellular antioxidants. CUR and N-CUR downregulated TLR4 and AP-1, and decreased the phosphorylation levels of p38 MAPK, JNK, and ERK1/2. In addition, CUR and N-CUR increased cardiac Bcl-2 and BAG-1, decreased Bax and caspase-3, and prevented DNA fragmentation. In conclusion, N-CUR prevents Cu cardiotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis, and modulating TLR4/NF-κB and MAPK signaling. The cardioprotective effect of N-CUR was more potent than the native form.

Cardiovascular Effects Induced by Fruit Peels from Passiflora edulis in Hypertensive Rats and Fingerprint Analysis by HPLC-ESI-MSn spectrometry.

Hypertension is a chronic disease and a global health problem. Due to its high prevalence, it constitutes the most important risk factor for cardiovascular disease. Fruit peels from Passiflora edulis fo. flavicarpa are rich in bioactive natural compounds that may have action in hypertension. This study aimed to perform a fingerprinting analysis of Passiflora edulis fruit peel extract and evaluate its actions on the cardiovascular system in an in vivo model. The extract was obtained from the dried and powdered fruit peels of Passiflora edulis. Glycoside flavonoids were identified in the extract by HPLC-ESI-MSn. The extract showed a significant hypotensive effect after 28days of treatment and improved vascular function in the mesenteric artery. This effect was verified by decreased vascular hypercontractility and increased vasorelaxant in response to sodium nitroprusside and acetylcholine. There was also a decrease in endothelial dysfunction, which can be attributed to nitric oxide's increased bioavailability. Thus, we hypothesize that all these effects contributed to a reduction in peripheral vascular resistance, leading to a significant hypotensive effect. These results are novel for fruit peels from P.edulis. Also, there was a decrease in plasma and cardiac malondialdehyde levels and an increase in glutathione, suggesting a reduction in oxidative stress, as well as an increase of anti-inflammatory cytokines such as IL-10 in the plasma. This study demonstrated that the extract can be a new source of raw material to be applied as food or medicine adjuvant for treating hypertension.

Effects of aerobic interval training on myocardial oxidative stress and inflammation in rats with myocardial infarction and its mechanism

Objective: The present study was to determine the effects of aerobic interval training (AIT) on the expressions of SIRT1, Nox4 and inflammatory factor in the heart of rats with myocardial infarction (MI). Methods: Male Sprague Dawley rats were randomly divided into sham-operated group (C), sedentary MI group (MI) and MI with AIT group (ME) (n=10). The MI model was established by ligation the left anterior descending coronary artery. Rats in C groups were subjected to the same surgery, but only threaded and not ligated. After surgery 1 week, rats in ME groups took adaptability training for 1 week, and then subjected to 4 weeks treadmill exercise training. After training, the hearts were collected for histological observation. The level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in heart was assessed by ultraviolet spectrophotometry. The activity of lactate dehydrogenase (LDH) was determined by enzyme linked immunosorbent assay. The expression of sirtuin1 (SIRT1) mRNA was examined by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of SIRT1, NADPH oxidase 4 (Nox4), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were detected by Western blotting. The levels of reactive oxygen species (ROS) were detected by dihydroethidium (DHE) staining. Results: Compared with the C group, the expression level of cardiac Nox4 protein was increased (P＜0.01), the level of MDA, activity of LDH and the level of ROS were increased significantly (P＜0.01), and the expressions of TNF-α and IL-1β protein were augmented in the heart of rats with MI (P＜0.01). However, the expressions of SIRT1 mRNA and protein and the activity of SOD were obviously decreased in MI group (P＜0.01). Furthermore, compared with the MI group, AIT increased the expressions of SIRT1 mRNA and protein and the activity of SOD in the heart of ME group (P＜0.01); Meanwhile, the expressions of cardiac Nox4, MDA level, LDH activity and ROS level were diminished in ME group (P＜0.01) as well as the decreased expressions of TNF-α and IL-1β protein (P＜0.01). SIRT1 expression was negatively related to the expressions of NOX4 and ROS. Conclusion: AIT obviously inhibited myocardial oxidative stress and inflammatory reaction, improved cardiac function in rats with MI, and the mechanism was closely related to the activation of SIRT1-Nox4-ROS signaling pathway.

Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats.

Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rodents were assigned to four groups (n = 7) and the treatments were given for 12 days as follows; Group 1 (control): were administrated normal saline, Group 2 (DAP control): were administrated DAP (10 mg/kg/day IP), Group 3 (ISO group): were administrated ISO (100 mg/kg, IP on the 11th and 12th days of the experiment), and Group 4 (DAP + ISO): co-treated with DAP plus ISO. The measured parameters were cardiac malondialdehyde (MDA), reduced glutathione (GSH), total nitrite/nitrate (NOx), catalase (CAT), serum cardiac biomarkers; CK-MB, ALT, LDH, and ALK-PH. Also, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), caspase-3 activity, and hepatic BAX and Bcl-2 were also assessed. Also, histological examination and vimentin immuno-expressions were studied. ISO group exhibited MI as evidenced by the elevation in serum cardiac biomarkers, MDA, NOx, IL-1β, TNF-α, and caspase-3 together with the reduction in GSH, Nrf2, HO-1 levels, and a faint vimentin immuno-reaction. Histological alterations revealing distorted cardiomyocytes; vacuolation, edema, pyknosis, and fragmentation were also noticed. DAP significantly ameliorated all the examined toxicity indicators. DAP revealed efficient ameliorative actions against ISO-caused MI by marked reduction in myocardial infarct size and suppressed oxidative stress, inflammation, and apoptosis via the up-regulation of the Nrf2/HO-1; TLR4/TNF-α signaling pathways.

Protective effects of rice bran hydrolysates on heart rate variability, cardiac oxidative stress, and cardiac remodeling in high fat and high fructose diet-fed rats

Objective: To examine the ameliorative effect of rice bran hydrolysates (RBH) on metabolic disorders, cardiac oxidative stress, heart rate variability (HRV), and cardiac structural changes in high fat and high fructose (HFHF)-fed rats. Methods: Male Sprague-Dawley rats were daily fed either standard chow diet with tap water or an HFHF diet with 10% fructose in drinking water over 16 weeks. RBH (500 and 1 000 mg/kg/day) was orally administered to the HFHF-diet-fed rats during the last 6 weeks of the study period. At the end of the treatment, metabolic parameters, oxidative stress, HRV, and cardiac structural changes were examined. Results: RBH administration significantly ameliorated metabolic disorders by improving lipid profiles, insulin sensitivity, and hemodynamic parameters. Moreover, RBH restored HRV, as evidenced by decreasing the ratio of low-frequency to high-frequency power of HRV, a marker of autonomic imbalance. Cardiac oxidative stress was also mitigated after RBH supplementation by decreasing cardiac malondialdehyde and protein carbonyl, upregulating eNOS expression, and increasing catalase activity in the heart. Furthermore, RBH mitigated cardiac structural changes by reducing cardiac hypertrophy and myocardial fibrosis in HFHF-diet-fed rats. Conclusions: The present findings suggest that consumption of RBH may exert cardioprotective effects against autonomic imbalances, cardiac oxidative stress, and structural changes in metabolic syndrome.

Pineapple consumption reduced cardiac oxidative stress and inflammation in high cholesterol diet-fed rats

BackgroundHypercholesterolemia is a major risk factor for cardiovascular disease. It has been reported that pineapple contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. No investigation exists concerning the effect of pineapple consumption modulating hypercholesterolemia-induced cardiac damage in high-cholesterol diet (HCD)-fed rats. This study evaluated the effect of pineapple consumption on lipid-lowering, cardiac oxidative stress and inflammation in HCD-fed rats.MethodsMale Sprague–Dawley rats were fed with HCD, in the presence and absence of Pineapple (Ananas comosus L.) cv. Pattavia powder for 8 weeks. Then, serum lipid profiles, liver and renal function tests, cardiac oxidative stress and pro-inflammatory cytokines were determined.ResultsDaily pineapple consumption reduced weight gain, serum lipid profiles, atherogenic coefficient (AC), cardiac risk ratio (CRR), and liver enzyme activity, without causing renal dysfunction. Pineapple consumption also restores cardiac protein carbonyl (cPC) content, reduces cardiac malondialdehyde (MDA), cardiac pro-inflammation cytokine IL-6 and IL-1β levels.ConclusionPineapple possesses antioxidant and lipid-lowering properties and daily consumption alleviates hypercholesterolemia-induced cardiac lipid peroxidation and pro-inflammation elevation in an in vivo model. This study demonstrates that pineapple is a potential candidate for cardioprotection against hypercholesterolemia.

Attenuation of doxorubicin-induced cardiotoxicity in Wistar rats by aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens

Ethnopharmacological relevanceChromolaena odorata (L) King and Robinson and Tridax procumbens Linn are used in traditional medicine in the treatment of diabetes mellitus and hypertension. Aim of the studyThis study investigated the potential protective role of aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens against cardiotoxicity induced by doxorubicin. Materials and methodsTo this end, their impact on plasma markers of cardiac integrity, cardiac markers of oxidative stress, cardiac lipids and electrolyte profiles, and activities of cardiac ATPases, lactate dehydrogenase and creatine kinase, were monitored in doxorubicin treated rats. Metformin (250 mg/kg body weight, orally) and both extracts (50, 75 and 100 mg/kg, orally) were daily administered for 14 days; while cardiotoxicity was induced with doxorubicin (15 mg/kg, intra-peritioneally, once on the 12th day of study). ResultsThe plasma activities of creatine kinase, lactate dehydrogenase and AST of Test control were significantly (p < 0.05) higher than those of the other groups. Also, the cardiac malondialdehyde, calcium, chloride, sodium, cholesterol and triglyceride concentrations of Test control were significantly (p < 0.05) higher than those of the others. However, the cardiac concentrations of ascorbic acid, reduced glutathione, magnesium and potassium, and cardiac activities of catalase, glutathione peroxidase, superoxide dismutase, Ca2+-ATPase, Mg2+-ATPase, Na+,K+-ATPase, creatine kinase and lactate dehydrogenase of Test control were significantly (p < 0.05) lower than those of the others. ConclusionsPre-treatment with the extracts and metformin elicited a cardioprotective effect, as indicated by the prevention of doxorubicin-induced cardiac oxidative stress and prevention of adverse alterations in plasma cardiac markers, cardiac lipids and electrolyte profiles, as well as improvement of the activities of cardiac ATPases, creatine kinase and lactate dehydrogenase.