Cardiac GSH Research Articles

Can Alpha-Pinene Prevent Methotrexate-Induced Cardiac and Hepatic Damage?

The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy.

In Silico and In Vivo Studies of β-Sitosterol Nanoparticles as a Potential Therapy for Isoprenaline-Induced Cognitive Impairment in Myocardial Infarction, Targeting Myeloperoxidase.

This study aimed to compare the effects of β-sitosterol nanoparticles (BETNs) and β-sitosterol (BET) on cognitive impairment, oxidative stress, and inflammation in a myocardial infarction (MI) rat model using in silico and in vivo methods. β-Sitosterol (BET) and myeloperoxidase (MPO) ligand-receptor binding affinities were evaluated using Autodock Vina for docking and Gromacs for dynamics simulations. BET nanoparticles, prepared via solvent evaporation, had their size confirmed by a nanoparticle analyzer. ISO-induced cognitive impairment in rats was assessed through Morris water maze and Cook's pole climbing tests. Oxidative stress, inflammation, and cardiac injury were evaluated by measuring GSH, SOD, MDA, MPO, CkMB, LDH, lipid profiles, and ECGs. Histopathology of the CA1 hippocampus and myocardial tissue was performed using H&E staining. In silico analyses revealed strong binding affinities between BET and MPO, suggesting BET's potential anti-inflammatory effect. BETN (119.6 ± 42.6 nm; PDI: 0.809) significantly improved MI-induced cognitive dysfunction in rats (p < 0.001 ***), increased hippocampal GSH (p < 0.01 **) and SOD (p < 0.01 **) levels, and decreased hippocampal MDA (p < 0.05 *) and MPO levels (p < 0.01 **). BETNs also elevated cardiac GSH (p < 0.01 **) and SOD (p < 0.01 **) levels and reduced cardiac MPO (p < 0.01 **), CkMB (p < 0.001 **) and LDH (p < 0.001 **) levels. It restored lipid profiles, normalized ECG patterns, and improved histology in the hippocampal CA1 region and myocardium. Compared with BET treatment, BETNs were more effective in improving cognitive impairment, oxidative damage, and inflammation in MI rats, suggesting its potential in treating cognitive dysfunction and associated pathological changes in MI.

Edaravone and obeticholic acid protect against cisplatin-induced heart toxicity by suppressing oxidative stress and inflammation and modulating Nrf2, TLR4/p38MAPK, and JAK1/STAT3/NF-κB signals

Cardiotoxicity is a significant adverse effect of cisplatin (CIS) that necessitates extensive medical care. The current study examines the cardioprotective effects of edaravone (EDV), obeticholic acid (OCA), and their combinations on CIS-induced cardiac damage. Rats were allocated into five groups: the normal control group, the remaining four groups received CIS (7.5 mg/kg, i.p.) as a single dose on the fifth day and were assigned to CIS, OCA (10 mg/kg/day) + CIS, EDV (20 mg/kg/day) + CIS, and the (EDV + OCA) + CIS group. Compared to the CIS-treated group, co-treating rats with EDV, OCA, or their combinations significantly decreased ALP, AST, LDH, CK-MB, and troponin-I serum levels and alleviated histopathological heart abnormalities. Biochemically, EDV, OCA, and EDV plus OCA administration mitigated cardiac oxidative stress as indicated by a marked decrease in heart MDA content with a rise in cardiac antioxidants SOD and GSH associated with upregulating Nrf2, PPARγ, and SIRT1 expression. Besides, it dampened inflammation by decreasing cardiac levels of TNF-α, IL-1β, and IL-6, mediated by suppressing NF-κB, JAK1/STAT3, and TLR4/p38MAPK signal activation. Notably, rats co-administered with EDV plus OCA showed noticeable protection that exceeded that of EDV and OCA alone. In conclusion, our study provided that EDV, OCA, and their combinations effectively attenuated CIS-induced cardiac intoxication by activating Nrf2, PPARγ, and SIRT1 signals and downregulating NF-κB, JAK1/STAT3, and TLR4/p38MAPK signals.Graphical Outlined diagram summarized the possible protective mechanisms of OCA and/or EDV against cisplatin-induced cardiac injury

Malva parviflora seed oil; Isolation, gas chromatographic profiling and its cardioprotective activity against myocardial infraction in animal model

Myocardial infarction (MI), one of the most perilous types of cardiac illness, carries a significant burden of mortality and morbidity. This study aims to shed light on the impact of Malva parviflora seed oil (MPSO) on plasma cardiac function tests, levels of cardiac inflammatory mediators, and the expression of cardiac miRNA140-5p and miRNA208b genes in a rat model of MI induced by isoproterenol (ISO). The methods involved the extraction of MPSO using hexane, with the determination of fatty acid contents accomplished through GC spectrometry. Adult albino rats, weighing 185 ± 7 g, were divided into five groups (n = 6): normal control rats, ISO-treated rats, ISO-treated rats with MPSO (157 and/or 314 mg/kg, respectively), and ISO-treated rats with omega (100 mg/kg, respectively) for a duration of four weeks. The results revealed that Malva parviflora seeds yielded 3.3 gm/100 dry seeds. Among the nine fatty acid components identified, coriolic acid was the most abundant (31.60 %), followed by pentadecanoic acid (30.05 %). The cardioprotective potential of MPSO was assessed in rats subjected to ISO-induced cardiac injury. Following 24 h of ISO treatment, rats displayed elevated levels of plasma cardiac troponin I (cTnI), troponin T (cTnT), lactate dehydrogenase (LDH), and B-Type Natriuretic Peptide (BNP), as well as cardiac BcL-2, P53, toll-like receptor 4 (TLR4), NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells), thiobarbituric acid reactive substances (TBARs), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), miRNA-140-5p, and miRNA-208b gene expression. Histopathological examination confirmed cardiac injury in ISO-treated rats. Furthermore, MPSO mitigated the elevation of cardiac enzymes and TBARS, as well as cardiac inflammatory mediators, while concurrently downregulating the expression levels of miRNA-140-5p and miRNA-208b genes. Conversely, the enhancement of cardiac GSH, SOD, and CAT activity demonstrated the antioxidant capabilities of MPSO against ISO-induced cardiac injury. Histopathological findings underscored MPSO's protective effect on cardiac tissue against oxidative damage in ISO-treated rats. In nutshel, the findings of this study unveil the cardioprotective and free radical scavenging attributes of MPSO in rats with ISO-induced cardiac damage. MPSO appears to provide cardiac protection against free radicals and inflammation induced by xenobiotics, potentially owing to its rich content of polyphenols, flavonoids, polyunsaturated fatty acids (PUFAs), and cyclopropenoid fatty acids.

PS-B11-1: ACETATE RESTORES CARDIAC METABOLIC FLEXIBILITY IN HIGH FAT DIET-INDUCED OBESITY THROUGH HDAC MODULATION

Objectives: Obesity remains a global epidemic and an independent risk factor for cardiovascular disease. Histone deacetylase (HDAC) activity has been implicated to increase adipogenic differentiation and consequent increase in adiposity, which are crucial features of obesity. Short chain fatty acids (SCFAs), which are potential HDAC inhibitors have been shown to be effective for glycemic/immune modulation. However, the involvement of HDAC or ANP/BNP in obesity-associated cardiac metabolic events is inconclusive. The present study hypothesized that cardiac metabolic inflexibility is dependent on cardiac ANP/BNP alteration and HDAC activity. We further sought to investigate the therapeutic potential of SCFA, acetate in high fat diet (HFD)-induced obese rat model. Methods: Adult male Wistar rats were assigned into groups (n = 6/group): Control, Obese, Sodium acetate (NaAc)-treated and Obese+ NaAc-treated groups received distilled water once daily (oral gavage), 40% HFD ad libitum, 200 mg/kg NaAc once daily (oral gavage) and 40% HFD+NaAc respectively. Results: The treatments lasted for 12 weeks. HFD resulted in increased food intake, body weight and cardiac mass. It also caused insulin resistance and enhanced Beta-cell function, increased fasting insulin, lactate, plasma and cardiac triglyceride, total cholesterol, glycogen content, lipid peroxidation, TNF-alpha, IL-6, HDAC and cardiac troponin T and gamma-glutamyl transferase and decreased plasma and cardiac GSH with unaltered cardiac ANP and BNP. However, these alterations were averted when treated with acetate. Conclusions: Taken together, these results indicate that obesity induces defective cardiac metabolic flexibility, which is accompanied by elevated level of HDAC and not ANP/BNP alteration. The results also suggest that acetate ameliorates obesity-induced cardiac metabolic inflexibility by suppression of HDAC and independent of ANP/BNP modulation.

Role of Atenolol and Carvedilol in Prevention of Adrenaline Induced Myocardial Infarction: A Comparative Study on Experimental Animal

Introduction: In some trials in United States of America (USA) and Bangladesh, vasodilating non selective β blockers (e.g. carvedilol, propranolol etc.) have been shown to be better tolerated than nonvasodilating β1 selective blocker (e.g. atenolol, metoprolol etc.) to prevent cardiovascular diseases (Coronary Heart Disease, Ischemic Heart Disease and other cardiovascular conditions) Objective: To compare the role of atenolol and carvedilol in the prevention of adrenaline induced myocardial infarction (MI) in experimental animal (rats). Materials and Methods: This experimental study was carried out in the Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka for a period of one year (from July 2014 to June 2015). Seventy two (72) healthy rats of Long Evan Norwegian strains, 3-4 months of ages of both sexes, weight between 180-220g were used. These rats were randomly selected and ethical issues were addressed. In this study cardio-protective effect was assessed by measuring the serum enzymes (CK-MB and AST) levels and antiperoxidative action was estimated by the hepatic and cardiac reduced glutathione (GSH) contents in experimentally (adrenaline) induced myocardial infarction. Results: Adrenaline (2mg/kg) induced myocardial damage in rat model was evaluated biochemically by significant (P&lt;0.001) increase in CK-MB and AST levels. Free radical production following adrenaline induced myocardial infarction was indirectly reflected by significant (P&lt;0.001) depletion in hepatic &amp; cardiac GSH contents. Cardio protection provided by atenolol and carvedilol pretreatment in adrenaline induced myocardial infraction was assessed by significant prevention of increase in serum CK-MB and AST levels. Antioxidant properties of carvedilol &amp; atenolol were evaluated by significantly (P&lt;0.001) increase in and significantly no (NS) change in GSH (hepatic &amp; cardiac) contents respectively. Conclusion: The study indicated that carvedilol (nonselective β blocker) through their antioxidant property in addition to α and β- blocking effect afforded more cardio protection than atenolol (selective β1adrenoceptor blocker) in experimental MI. JAFMC Bangladesh. Vol 17, No 2 (December) 2021: 65-70

Cardioprotective and Antioxidant Efficiency of Balanites aegyptiaca Extract Against Doxorubicin® Complication.

&lt;b&gt;Background and Objective:&lt;/b&gt; The use of Doxorubicin&lt;sup&gt;®&lt;/sup&gt; (Doxo) in the treatment of different tumours is restricted due to its cardiotoxicity. The objective of this study was to determine the protective effect of&lt;i&gt; Balanites aegyptiaca&lt;/i&gt; extract against cardiotoxicity induced by Doxorubicin&lt;sup&gt;®&lt;/sup&gt; in male rats. &lt;b&gt;Materials and Methods:&lt;/b&gt; Adult male rats (140-160) were parted into 6 groups (10 animals each) as follows: Group (1) Normal rats the control, group (2) Rats were administered BAE (200 mg kg&lt;sup&gt;1&lt;/sup&gt;) orally for 4 weeks, group (3) Rats were treated IP with the anticancer drug (Doxorubicin&lt;sup&gt;®&lt;/sup&gt;) at the dose of (0.5 mg kg&lt;sup&gt;1&lt;/sup&gt;) for 4 weeks, group (4) Administrated orally with BAE in combination with Doxo injection for 4 weeks, group (5) Rats orally with BAE before intoxication with Doxo for 4 weeks and finally group (6) Animals post-administration of BAE for 4 weeks after intoxication with Doxo. After 4 weeks of injections. &lt;b&gt;Results:&lt;/b&gt; Revealed that BAE succeeded to decline the Doxorubicin cardiotoxicity, this was evidenced by the significant reduction of serum LDH, CK-MB, total cholesterol, triglycerides, HDL, TNF-α, IL-1β and IL-6 as well as cardiac MDA and nitric oxide levels coupled with marked improvement in serum LDL, PON1 as well as cardiac GSH, SOD and CAT. Moreover, the BAE induced prominent regeneration of the cardiac muscle. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Balanites aegyptiaca&lt;/i&gt; extract may be a promising cardio-protector against Doxorubicin&lt;sup&gt;®&lt;/sup&gt; toxicity mediated through their antioxidant and radical scavenging activities.

Ficus sur methanol leaf extract ameliorated doxorubicin-induced cardio-renal damage in Wistar albino rats

Doxorubicin is an effective and still-used antineoplastic agent. However, the clinical use of doxorubicin is marred by life-threatening cardiotoxicity and nephrotoxicity. Free radicals have been implicated in the toxicity of doxorubicin. The aim of this study was to determine the phytochemical contents and protective effects of methanol extract of Ficus sur (MEFS) in doxorubicin-induced oxidative damage in Wistar albino rats, using biomarkers of cardiac, renal functions and oxidative stress as indicators. Phytochemical analyses revealed that MEFS is rich in tannins, alkaloid, saponins, flavonoids, but low in steroids. Acute toxicity studies show that MEFS was non-toxic up to 5000mg/kg b.w of Wistar rats. Administration of doxorubicin led to a significant (P&lt; 0.05) increase in Creatine kinase (CK-MB), troponin, creatinine, urea and MDA concentrations. Sodium and potassium concentrations were not significantly (P&gt;0.05) affected. Cardiac and renal superoxide dismutase (SOD), catalase and glutathione (GSH) were also significantly reduced. Results also show that pre-administration of MEFS was cardio- and nephroprotective in doxorubicin oxidative damage as evidenced by significant (P&lt;0.05) reduction of elevated troponin, CK-MB, creatinine and urea concentrations. Concentrations of renal and cardiac SOD, catalase and GSH were also significantly (p&lt;0.05) increased by MEFS compared to doxorubicin-treated group. Cardiac and renal MDA concentrations were significantly reduced. It may be concluded that protective effects of MEFS on doxorubicin toxicity may be due to the antioxidant properties of MEFS.

Effects of methanolic leaf extract of Kigelia africana on hemodynamic parameters and redox status of normotensive wistar rats

Kigelia Africana has a rich history of ethnobotanical usage in the treatment of a wide range of illnesses andcomplications like hypertension, cancer and microbial infections in south western Nigeria. The present work sought to investigate the effects of methanolic leaf extract of Kigelia Africana on the blood pressure and biochemical indices of normotensive albino rats. Twenty five male albino Wistar rats, weighing between 180-200g, and divided into five groups (I-V) of five animals each were used for the experiment. GroupsII – V were administered 1mg/kg b.w ramipril, 25-, 50- and 100mg/kg b.wKigelia Africana respectively by oral gavage for 14 consecutive days. Group I received vehicle (1 mg/kg distilled water) only throughout the duration of the experiment and served as control. Twenty-four hours after the last administration, the blood pressure was determined before sacrificing the animals following anesthesia. The activities of serum biomarkers (aspartate aminotransferase AST, total protein TP, alanine aminotransferase ALT, alkaline phosphatase ALP), serum lipid profile; (cholesterol TC, low/very low density lipoprotein LDL-c/VLDL-c, high density lipoprotein HDL and triglyceride TG) and cardiac antioxidant indices (catalase CAT, superoxide dismutase SOD and glutathione GSH) were determined. Administration of ramipril (1mg/kg b.w) and all dosages of Kigelia africana (25, 50 and 100mg/kg b.w) caused significant (P&lt;0.05) decrease in the blood pressure of the animals when compared to the control. The values obtained further showed that ramipril and the extract (at all dosages) caused significant reduction in TC, TG, LDL-c and VLDL-c and coronary risk index, CRI while there was significant increase in the level of HDL when compared to the control. All dosages of Kigelia africana extract resulted in significant (P&lt;0.05) decrease in serum activities of AST, ALT and ALP when compared with the control. The significant (P&lt;0.05) increases in cardiac catalase activity and GSH concentration recorded in rats treated with Kigelia africana (25, 50 and 100mg/kg b.w.) were comparable with those administered the reference drug, ramipril (1 mg/kg). Cardiac SOD activity was however decreased in rats administered extract (25, 50 or 100 mg/kg b.wt) and ramipril (1mg/kg bw). The results suggest the hypolipidemic, hypotensive and antioxidant properties and of methanolic extract of Kigelia africana leaf and lend support to the ethnobotanical usage of the leaf in the treatment of hypertension.

Induction of Glutathione Synthesis Provides Cardioprotection Regulating NO, AMPK and PPARa Signaling in Ischemic Rat Hearts.

Glutathione (GSH) is essential for antioxidant defence, and its depletion is associated with tissue damage during cardiac ischemia-reperfusion (I/R). GSH is synthesized by the glutamate-cysteine ligase enzyme (GCL) from L-cysteine, which alternatively might be used for hydrogen sulfide production by cystathionine-gamma-lyase (CSE). Here, we have investigated whether in vivo treatment with L-cysteine and an inhibitor of CSE,D,L-propargylglycine (PAG), can modulate cardiac glutathione and whether this treatment can influence heart resistance to I/R in a Langendorff isolated rat hearts model. Pretreatment with PAG + L-cysteine manifested in pronounced cardioprotection, as there was complete recovery of contractile function; preserved constitutive NOS activity; and limited the production of reactive oxygen and nitrogen species in the ischemized myocardium. Cardiac GSH and GSSG levels were increased by 3.5- and 2.1-fold in PAG + L-cysteine hearts and were 3.3- and 3.6-fold higher in PAG + L-cysteine + I/R compared to I/R heart. The cardioprotective effect of PAG + L-cysteine was completely abolished by an inhibitor of GCL, DL-buthionine-(S,R)-sulfoximine. Further analysis indicated diminished fatty acid β-oxidation, increased glucose consumption and anaerobic glycolysis, and promoted OXPHOS proteins and SERCA2 in PAG + L-cysteine + I/R compared to the I/R group. PAG + L-cysteine inhibited PPARα and up-regulated AMPK signalling in the heart. Thus, induction of glutathione synthesis provided cardioprotection regulating NO, AMPK and PPARa signaling in ischemic rat hearts.

Berberine Protests the Heart from Ischemic Reperfusion Injury via Interference with Oxidative and Inflammatory Pathways.

Background:Ischemia and reperfusion (I/R) is a pathological condition characterized by an initial restriction of blood supply to an organ followed by the subsequent restoration of perfusion and concomitant reoxygenation.Objective:The aim of the study is to assess the possible cardioprotective potential effect of berberine in myocardial ischemia reperfusion injury induced by ligation of coronary artery in a male rat model.Methods:Total amount of 28 adult male albino rats were randomized into 4 equal groups: 1) Sham group, rats underwent the same anesthetic and surgical procedure as the control group except for LAD ligation; 2), Active control group, rats subjected to regional ischemia for 30 min by ligation of LAD coronary artery and reperfusion for 2 hours, 3), Control vehicle group, rats received dimethyl sulphoxide (DMSO) (vehicle of berberine) via IP route and subjected to ischemia for 30 minutes before ligation of LAD coronary artery & reperfusion for 2 hr; 4), Berberine treated group, rats pretreated with berberine10 mg/kg via IP injection 30minutes before ligation of LAD coronary artery & then subjected to reperfusion for 2 hr.Results:In the control group, as compared with sham, tissue TNF-α, IL-6, IL-10, caspase-3 and BAX, plasma cTn-T and serum MDA significantly increased (P<0.05), while serum GSH significantly decreased (P<0.05). The histopathological control group showed a significant cardiac injury (P<0.05) compared with the sham group. Berberine significantly counteracted (P<0.05) the increase of TNF-α, IL-6, caspase-3 and BAX and counteracted the increase in plasma cTn-T and serum MDA. Berberine produces a significant elevation (P<0.05) in cardiac IL-10 and serum GSH with a significant reduction in (P<0.05) cardiac injury.Conclusion:Berberine attenuates myocardial I/R injury in male rats via interfering with inflammatory reactions and apoptosis which were induced by I/R injury.

Preparation of Ginkgolide Solid Dispersions with Low-Molecular-Weight Chitosan and Assessment of their Protective Effect on Isoproterenol- Induced Myocardial Injury.

Ginkgolides are widely used in cardio-protective therapy; however, poor bioavailability currently limits their application. The purpose of this study was to demonstrate whether solid dispersions prepared with Low- Molecular-Weight Chitosan (LMWC) could improve the protective effect of ginkgolides on Myocardial Injury (MI). Ginkgolide Solid Dispersions (GKSD) were prepared with LMWC. Their properties were then characterized using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. In vivo pharmacokinetic studies were performed in rats, and the protective effect of GKSD on MI was investigated by western blotting and immunohistochemical analyses. Drug dissolution testing showed that GDSD were released at a significantly higher rate than ginkgolides, dissolved by alternative methods, suggesting that LMWC facilitates the release of ginkgolides. Differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy all showed that GKSD was amorphous. In-vivo testing revealed larger AUC0-t, higher Cmax, and shorter Tmax for GKSD compared to that in original ginkgolides. Myocardial injury was induced in rats with isoproterenol to test the protective effect of GKSD. GKSD alleviated MI and reduced myocardial fibrosis, as observed by Hematoxylin and Eosin staining. Compared with the crude drug group, the secretion of malonyl dialdehyde and nitric oxide and expression of NOX-2 and NOX-4 were lower. The activities of the cardiac marker enzymes SOD, CAT, GPX, GPX-1, and GSH were higher in GKSD-administered rats, indicating a beneficial effect of GKSD in eliminating free radicals during myocardial injury. Additionally, western blotting and immunohistochemical analysis showed that GKSD markedly reduced the expression of signaling proteins RHOA, ROCK1, ROCK2, and RAC1. Solid dispersions prepared with low molecular weight chitosan improved the oral bioavailability of ginkgolide and enhanced its protective effect on myocardial injury.

The cardioprotective potential of Tadalafil in myocardial ischemia/reperfusion

The objective of this study is to assess the potential protective effect of Tadalafil on myocardial ischemia reperfusion injury induced by LAD ligation, 28 male rats were randomized into 4 groups (7 rats per group); Sham, rats underwent the same anesthetic and surgical procedure except for LAD ligation; control, rats underwent LAD ligation for 30 minutes and reperfusion for 2 hours; vehicle, rats treated with 10% DMSO, the Tadalafil solvent 30 minutes before the ligation; Tadalafil group, rats pretreated with Tadalafil1mg/kg i.p 30 minutes before ligation. In control group, as compared with sham, tissue TNF-α, IL-6, IL-10, caspase-3 and BAX, plasma cTn-T and serum MDA significantly increased (P&lt;0.05), while serum GSH significantly decreased (P&lt;0.05). Histopathologically, control group showed a significant cardiac injury (P&lt;0.05) compared with sham group. Tadalafil significantly counteracted (P&lt;0.05) the increase of TNF-α, IL-6, caspase-3 and BAX and counteracted the increase in plasma cTn-T and serum MDA. Tadalafil produces a significant elevation (P&lt;0.05) in cardiac IL-10 and serum GSH with significant reduction in (P&lt;0.05) cardiac injury. In We concluded that Tadalafil attenuates myocardial I/R injury in male rats through interfering with inflammatory reactions and apoptosis .

Egg white consumption increases GSH and lowers oxidative damage in 110-week-old geriatric mice hearts

The number of geriatrics with an advanced age is rising worldwide, with attendant cardiovascular disorders, characterized by elevated oxidative stress. Such oxidative stress is accelerated by an age-related loss of critical antioxidants like glutathione (GSH) and dietary solutions to combat this loss does not exist. While egg white is rich in sulphur amino acids (AAs), precursors for GSH biosynthesis, whether they can increase sulphur AA in vivo and augment GSH in the aged myocardium remain unclear. We hypothesized that egg white consumption increases GSH and reduces oxidative damage and inflammation in the geriatric heart. To this end, 101-102 week-old mice were given a AIN 76A diet supplemented with either 9% w/w egg white powder or casein for 8 weeks. Subsequent analysis revealed that egg white increased serum sulphur AA and cardiac GSH, while reducing the cysteine carrying transporter SNAT-2 and elevating glutamine transporter ASCT2 in the heart. Increased GSH was accompanied by elevated expression of GSH biosynthesis enzyme glutathione synthase as well as mitochondrial antioxidants like superoxide dismutase 2 and glutathione peroxidase 1 in egg white-fed hearts. These hearts also demonstrated lower oxidative damage of lipids (4-hydroxynonenal) and proteins [nitrotyrosine] with elevated anti-inflammatory IL-10 gene expression. These data demonstrate that even at the end of lifespan, egg whites remain effective in promoting serum sulphur AAs and preserve cardiac GSH with potent anti-oxidant and mild anti-inflammatory effects in the geriatric myocardium. We conclude that egg white intake may be an effective dietary strategy to attenuate oxidative damage in the senescent heart.

Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia-reperfusion injury through depletion of glutathione.

Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague-Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (&lt;1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.

Role of Carvedilol in Prevention of Adrenaline Induced Myocardial Infraction in Experimental Animal

Introduction: Acute myocardial infarction (AMI) is the most important form of ischemic heart disease (IHD). Coronary artery disease (CAD) is an increasingly important medical and public health problem and is the leading cause of mortality in Bangladesh. AMI is the rapid development of myocardial necrosis caused by a critical imbalance between the oxygen supply and demand of the myocardium. Total occlusion of the coronary arteries for more than 4-6 hrs results in irreversible myocardial necrosis, but reperfusion within this period can salvage the myocardium and reduce morbidity and mortality.&#x0D; Objectives: To assess the role of carvedilol in prevention of adrenaline induced cardiac damage in experimental animal.&#x0D; Materials and Methods: This experimental study was carried out in the department of pharmacology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka for a period of One year spanning from July 2004 to June 2005. Fifty two healthy rats of Long Evan Norwegian strains, 3-4 months of ages of both sexes, weight between 180-220g were used. The experiment was divided into two parts: Part-I and Part-II. Thirty two rats were selected for Part-I experiment and subdivided into Group-I and Group-II. In Part-II experiment, 20 rats were selected and placed as Group-III. Group-I (12 rats) of control group was treated with 02 doses of inj distilled water (D/W) subcutaneously (S.C.) 24 hrs apart and serum creatine kinase-MB (CK-MB) level and hepatic and cardiac reduced glutathione (GSH) contents were estimated from 06 (Group-Ia) rats after 12 hrs and serum aspartate aminotransferase (AST) level and hepatic and cardiac reduced GSH contents were estimated from 06 (Group-Ib) rats after 24 hrs of 2nd inj of D/W. Group-II (20 rats) was treated with 02 doses of inj adrenaline (2mg/kg) S.C. in 24 hrs interval and in above mentioned way serum CK-MB level, GSH (hepatic and cardiac) contents and serum AST and GSH (hepatic and cardiac) contents were estimated 12 hrs and 24 hrs after the 2nd inj of adrenaline respectively. In experimental group (Group-III) all the rats (20) were treated with carvedilol (1 mg/kg) orally for 14 consecutive days and then were given 02 doses of inj adrenaline with the interval of 24 hrs and again serum CK-MB level and GSH (hepatic and cardiac) contents were estimated from half of the rats (10) after 12 hrs of injection and serum AST level and GSH (hepatic and cardiac) contents were measured from half of the rats (10) after 24 hrs of 2nd injection of adrenaline.&#x0D; Results: Adrenaline (2mg/kg) induced myocardial damage was evaluated biochemically by significant (P˂0.001) increase in CK-MB and AST levels. Free radical production following adrenaline induced myocardial damage was reflected by significant (P˂0.001) depletion in hepatic and cardiac reduced glutathione (GSH) contents. Cardioprotection provided by carvedilol pretreatment in adrenaline induced myocardial infarction was assessed by significant prevention of increase in serum CK-MB and AST levels. Antioxidant property of carvedilol was evaluated by significant (P&lt;0.001) prevention of depletion in hepatic and cardiac GSH contents. The results of the study indicated that carvedilol pretreatment provided effective prevention in adrenaline induced myocardial damage and also provided effective antioxidative action.&#x0D; Conclusion: This study indicated that adrenaline administration induced myocardial damage as evidenced by increase in serum CK-MB and AST levels which was associated with free radical production as reflected by depletion in hepatic and cardiac GSH contents. It was observed that carvedilol through their antioxidant property in addition to their β-blocking effect prevents free radical mediated injury of catecholamine assault following MI.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.12(2) 2016: 127-134

PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals

Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out.Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia.Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms.

Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in adult male albino rats.

The use of doxorubicin (DOX) as an antitumor therapeutic agent is limited due to its cardiotoxic effects. Metformin (Met) and sitagliptin (Sitg) are suggested to improve cardiac function. The present study aimed to determine the potential protective effects of Met and Sitg on DOX-induced cardiotoxicity. Rats were divided into six groups: groups I, II, and III received normal saline, Met, and Sitg, respectively. Groups IV, V, and VI received DOX only, Met + DOX, and Sitg + DOX, respectively. Heart tissue was used for biochemical assays which measured cardiac reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and tumor necrosis factor α (TNF-α). Serum creatinine kinase (CK) and lactate dehydrogenase (LDH) were also measured. The heart apex was prepared for histological (hematoxylin and eosin) and immunohistochemical examination. Intoxication of DOX was associated with a significant elevation in serum CK-MB and LDH, reduction in cardiac GSH, and increased TBARS and TNF-α compared to the controls. Administration of Met or Sitg to DOX-intoxicated rats suppressed serum CK-MB and LDH. Moreover, cardiac GSH was elevated with decreased TBARS and TNF-α. These results were confirmed by histological study. Met and Sitg caused inhibition of caspase 3 and upregulation of B-cell lymphoma 2 (Bcl-2) expression in DOX-intoxicated animals. Sitg was found to exert a significantly better protective effect compared to that of Met. It was concluded that Sitg might be more effective than Met in reducing myocardial injury in DOX-induced cardiotoxicity in rats.

Pentoxifylline abrogates cardiotoxicity induced by the administration of a single high dose or multiple low doses of doxorubicin in rats.

Doxorubicin (DOX) possesses a broad-spectrum antineoplastic activity; however, its clinical application is impeded by cardiotoxicity. This study aimed to investigate the protective effect of pentoxifylline (PXF), which possesses antioxidant and anti-inflammatory properties against cardiotoxicity induced by a single high dose (15 mg/kg, i.p.) or multiple low doses (2.5 mg/kg, i.p., three times per week for 2 weeks) of DOX. At the end of the experimental period, the serum creatine kinase (CK)-MB and lactate dehydrogenase (LDH) activities were measured. The hearts were then removed for evaluating TNF-α, NO, malondialdehyde (MDA), and reduced glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and the expression of iNOS, NF-κB, Fas ligand (FasL), and caspase-3. The administration of DOX in both dose regimens caused increases in serum CK-MB and LDH activities, in cardiac TNF-α, NO and MDA levels, as well as in the cardiac expression of iNOS, NF-κB, FasL and caspase-3, whereas it significantly reduced the cardiac GSH level, as well as SOD and CAT activities (P < 0.05). Prophylactic treatment of rats with PXF diminished DOX-induced alterations in theses parameters. Our results warrant the clinical use of PXF as an adjuvant therapy to abrogate cardiotoxicity of DOX and extend its clinical applications.

The Cardioprotective Effect Of Selenium In Myocardial Ischemia Reperfusion Injury

The objective of the current study is to assess the possible cardioprote-ctive effect of selenium in myocardial ischemia reperfusion injury induced by ligation of coronary artery in a male rat model. 24 adult male spraguedawley rats were randomized into 4 equal groups: (1), Sham group, rats underwent the same anesthetic and surgical procedures as the control group except for LAD ligation; (2), Active control group, rats subjected to regional ischemia for 30 min by ligation of LAD coronary artery and reperfusion for 2 hours; (3), Control vehicle group, rats received D.W (vehicle of selenium) via IP route and subjected to ischemia for 30 minutes before ligation of LAD coronary artery &amp; reperfusion for 2 hr; (4), Seleniumtreated group, rats pretreated with selenium5mg/kg via IP injection 30minutes before ligation of LAD coronary artery &amp; then subjected to reperfusion for 2 hr. In control group, as compared with sham, tissue TNF-α, IL-6, IL-10, caspase-3 and BAX, plasma cTn-T and serum MDA significantly increased (P&lt;0.05), while serum GSH significantly decreased (P&lt;0.05). Histopathologically, control group showed a significant cardiac injury (P&lt;0.05) compared with sham group. Selenium significantly counteracted (P&lt;0.05) the increase of TNF-α, IL-6, caspase-3 and BAX and counteracted the increase in plasma cTn-T and serum MDA. Selenium produces a significant elevation (P&lt;0.05) in cardiac IL-10 and serum GSH with significant reduction in (P&lt;0.05) cardiac injury. In Conclusions, Selenium minimizes myocardial I/R injury in male rats via interfering with inflammatory reactions and apoptosis which were induced by I/R injury .