Newly synthesized acridone derivatives targeting lung cancer: A toxicity and xenograft model study.

AKT is one of the overexpressed targets in nonsmall cell lung cancer (NSCLC) and plays an important role in its progression and offers an attractive target for the therapy. The PI3K/AKT/mTOR pathway is upregulated in NSCLC. Acridone is an important heterocycle compound which treats cancer through various mechanisms including AKT as a target. In the present work, the study was designed to evaluate the safety profile of three acridone derivatives (AC-2, AC-7, and AC-26) by acute and repeated dose oral toxicity. In addition to this, we also checked the pAKT overexpression and its control by these derivatives in tumor xenograft model. The results from acute and repeated dose toxicity showed these compounds to be highly safe and free from any toxicity, mortality, or significant alteration in body weight, food, and water intake in the rats. In the repeated dose toxicity, compounds showed negligible variations in a few hematological parameters at 400 mg/kg. The histopathology, biochemical, and urine parameters remained unchanged. The xenograft model study demonstrated AC-2 to be inhibiting HOP-62 induced tumor via reduction in p-AKT1 (Ser473) expression significantly. In immunofluorescence staining AC-2 treated tissue section showed 2.5 fold reduction in the expression of p-AKT1 (Ser473). Histopathology studies showed the destruction of tumor cells with increased necrosis after treatment. The study concluded that AC-2 causes cell necrosis in tumor cells via blocking the p-AKT1 expression. The findings may provide a strong basis for further clinical applications of acridone derivatives in NSCLC.

Exploring progress in iron supplement formulation approaches for treating iron deficiency anemia through bibliometric and thematic analysis.

Anemia is a severe health issue that affects around one-third of the global population. Therefore, the present study aims to conduct a bibliometric analysis to investigate the research trends regarding advancements on iron formulations in treating iron deficiency anemia via oral or parenteral route. This study adopts thematic and bibliometric methods on existing research on novel iron formulations. It also provides perspective into the existing understanding on treatment strategies for iron deficiency anemia. This study is conducted on 543 papers on various ferrous and ferric formulations used in the treatment of iron deficiency anemia. The study period is from 1977 to 2022, and the papers are identified from the Scopus database. The bibliometric analysis was carried out using the R tool's Bibliometrix package. The study discusses performance analysis, including annual publications, geographic analysis, relevant affiliations, journal analysis, and citation analysis. In addition, the conceptual structure, including the co-occurrence network, thematic map, thematic evolution, intellectual structure highlighting co-citation analysis, and social structure depicting the collaboration network and collaboration world map, are presented. The results showed increased research on formulation strategies for the treatment of iron deficiency anemia from 2010 onwards. The top 5 contributing countries are the USA, Italy, India, Germany, and the UK, and peer-reviewed journals from the area of nutrition. The most trending areas of study are iron deficiency anemia in pregnancy, chronic kidney diseases, inflammatory bowel diseases, and various intravenous formulations used in its treatment. The authors from Europe collaborate the most with authors from other countries. The study concludes that a safer and more effective iron formulation is needed to reduce the prevalence of anemia. The findings of the study are helpful in advancing research on innovative formulations for treating iron deficiency anemia. The insights from the study are helpful to policymakers in designing specific health policies and investing more in research and development of novel formulations for the treatment of iron deficiency anemia.

Targeting the vivid facets of apolipoproteins as a cardiovascular risk factor in rheumatoid arthritis.

Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.

Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies.

Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates a time-restricted event where the imbalance between pro- and antiangiogenic factors results in the transition from prevascular hyperplasia to outgrowing vascularized tumor, which eventually leads to the malignant cancer progression. In the last decade, molecular players, i.e., angiogenic biomarkers and underlying molecular pathways involved in tumorigenesis, have been intensely investigated. Disrupting the initiation and halting the progression of angiogenesis by targeting these biomarkers and molecular pathways has been considered as a potential treatment approach for tumor angiogenesis. This review discusses the currently known biomarkers and available antiangiogenic therapies in cancer, i.e., monoclonal antibodies, aptamers, small molecular inhibitors, miRNAs, siRNAs, angiostatin, endostatin, and melatonin analogues, either approved by the U.S. Food and Drug Administration or currently under clinical and preclinical investigations.

Reactive oxygen species (ROS)-mediated oxidative stress in chronic liver diseases and its mitigation by medicinal plants.

Reactive oxygen species (ROS) play a crucial role in cell survival regulation, and its low levels may act as indicators to encourage cellular proliferation. In contrast, elevated levels of ROS may lead to apoptosis. Stability between generating and eliminating ROS allows the retention of effective functioning of redox-sensitive signaling proteins under physiologic conditions. Cells typically maintain redox homeostasis to guarantee appropriate responses to internal and external stimuli. However, oxidative stress occurs when the oxidation product level exceeds the number of standard antioxidant systems. ROS can cause harm to all types of hepatic cells, including endothelial cells, hepatocytes, Kupffer cells, and stellate cells. High levels of ROS may lead to tissue edema, ischemia, fibrosis, cell death, or malignant transformation and may eventually lead to complete tissue damage. Antioxidants in our body exist in a homeostatic balance with other enzymes involved in the repair of cellular functions in addition to the non-enzymatic molecules such as urate, bilirubin, several vitamins, and reduced glutathione to maintain the levels of ROS in the interest of cellular homeostasis. This balance may, however, get disturbed in case of acute or chronic liver injury due to the accumulation of ROS. In the current manuscript, we aim to review the relevance of oxidative stress and its indicator of liver injury in chronic liver diseases such as alcoholic and non-alcoholic fatty liver diseases and hepatitis. Since reactive oxidation species may also lead to lipid peroxidation and promote ferroptosis, we have also evaluated their impact on epigenetic modifications, such as oxidative damage to histone proteins and DNA methylation, and the differential expression of genes related to cellular injury. We also want to highlight the potential of traditional herbal medicines as redox regulators for managing chronic liver diseases.

A pharmacological review on SIRT 1 and SIRT 2 proteins, activators, and inhibitors: Call for further research.

Sirtuins or Sir (Silent information regulator) are NAD+-dependent enzymes playing an important part in the pathogenesis and treatment of various disorders. They have ubiquitously expressed protein deacetylases. They are implicated in several cellular activities like DNA repair, cellular metabolism, mitochondrial function, and inflammation. Deletion of sirtuin protein, SIRT1 in the organs like brain, heart, liver and pancreas can cause inflammation and increases the level of free radical ions causing oxidative stress. Inflammation and oxidative stress are closely associated with pathophysiological events in many chronic diseases, like diabetes, cancer, cardiovascular, osteoporosis, and neurodegenerative diseases. Modulation of SIRT1 gene expression might help in preventing the progression of chronic diseases related to the brain, heart, liver, and pancreas. SIRT2 proteins play an essential role in tumorigenesis, including tumor-suppressing and tumor-promoting functions. Sirtuin activators are molecules that upregulate the activity of Sirtuins in the body. Their multifaceted uses have surprised the global scientific community. They are found to control obesity, lower cardiac risks, battle cancer, etc. This article provides an update on the pharmacological effect of SIRT1 and SIRT 2 proteins, their activators and inhibitors, and their molecular mechanism. It provides novel insights for future research in targeted therapy and drug development.

Metabolomics and EMT Markers of Breast Cancer: A Crosstalk and Future Perspective.

Cancer cells undergo transient EMT and MET phenomena or vice versa, along with the parallel interplay of various markers, often correlated as the determining factor in decoding metabolic profiling of breast cancers. Moreover, various cancer signaling pathways and metabolic changes occurring in breast cancer cells modulate the expression of such markers to varying extents. The existing research completed so far considers the expression of such markers as determinants regulating the invasiveness and survival of breast cancer cells. Therefore, this manuscript is crosstalk among the expression levels of such markers and their correlation in regulating the aggressiveness and invasiveness of breast cancer. We also attempted to cover the possible EMT-based metabolic targets to retard migration and invasion of breast cancer.

Effect of parthenolide, an NLRP3 inflammasome inhibitor, on insulin resistance in high-fat diet-obese mice.

The activation of Nod-like receptor proteins (NLRP3) containing the pyrin domain inflammasome is a hallmark of the pathogenesis of metabolic disorders. Inhibition of the NLRP3 inflammasome by phytoconstituents has been attempted as a strategy to mitigate these disorders. Therefore, the present study aimed to evaluate the efficacy of an NLRP3 inflammasome inhibitor, parthenolide (PN; 5 mg/kg i.p.) against inflammation and insulin resistance in high-fat diet (HFD) - obese mice. Treatment with PN and pioglitazone (PIO; 30 mg/kg p.o.) attenuated lipopolysaccharide (LPS; 1 ng/ml) - induced elevation of tumor necrosis factor-α and interleukin-1ß in mouse peritoneal macrophages in a dose-dependent manner. Sixty days of PN and PIO treatment marginally reduced obesity-induced insulin resistance in HFD-obese mice. PN treatment also decreased blood glucose from 14th to 60th day, supporting the hypothesis of simultaneous attenuation of inflammation and insulin resistance in obese mice. Thus, PN treatment was also evident with significant improvement in glucose tolerance and peripheral insulin resistance validated through the respective tolerance tests. Therefore, the present study suggests that PN, an NLRP3 inflammasome inhibitor, could be a possible therapeutic agent for attenuating obesity-induced insulin resistance.

Facile synthesis of bromelain copper nanoparticles to improve the primordial therapeutic potential of copper against acute myocardial infarction in diabetic rats.

Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) - induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.

Crosstalk between GSK-3ß-actuated molecular cascades and myocardial physiology.

The finding of "glycogen synthase kinase-3" (GSK-3) was initially identified as a protein kinase that phosphorylate and inhibited glycogen synthase. However, it was soon discovered that GSK-3 also has significant impact in regulation of truly astonishing number of critical intracellular signaling pathways ranging from regulation of cell growth, neurology, heart failure, diabetes, aging, inflammation, and cancer. Recent studies have validated the feasibility of targeting GSK-3 for its vital therapeutic potential to maintain normal myocardial homeostasis, conversely, its loss is incompatible with life as it can abrupt cell cycle and endorse fatal cardiomyopathy. The current study focuses on its expanding therapeutic action in myocardial tissue, concentrating primarily on its role in diabetes-associated cardiac complication, apoptosis and metabolism, heart failure, cardiac hypertrophy, and myocardial infarction. The current report also includes the finding of our previous investigation that has shown the impact of GSK-3ß inhibitor against diabetes-associated myocardial injury and experimentally induced myocardial infarction. We have also discussed some recent identified GSK-3ß inhibitors for their cardio-protective potential. The crosstalk of various underlying mechanisms that highlight the significant role of GSK-3ß in myocardial pathophysiology have been discussed in the present report. For these literatures, we will rely profoundly on our previous studies and those of others to reconcile some of the deceptive contradictions in the literature.

Chemoprophylactic activity of nitazoxanide in experimental model of mammary gland carcinoma in rats.

The current study focuses on the evaluation of the chemoprophylactic activity of nitazoxanide against the mammary gland carcinoma in experimental rats. The experimental protocol involves total 50 female Wistar albino rats of body weight 120-150 g, which were randomly categorized into five groups; Normal control (1% w/v carboxymethyl cellulose, p.o.); Toxic control (N-methyl-N-nitrosourea, MNU, 47 mg/kg i.v.); Standard (MNU, 47 mg/kg i.v. + tamoxifen, 1 mg/kg p.o.); Treatment 1 (MNU, 47 mg/kg i.v. + NTZ low-dose, 25 mg/kg p.o.); and Treatment 2 (MNU, 47 mg/kg, i.v. + NTZ high-dose, 50 mg/kg p.o.). The mammary gland carcinoma was induced by a single tail vein intravenous injection of MNU at a 47 mg/kg dose. Seven days after MNU administration, daily dosing of nitazoxanide and tamoxifen was initiated till 110th day in respective groups. The MNU toxicity was apparent with the altered electrocardiogram and heart rate variability, increased number of alveolar bud count, differentiation score, and upregulated antioxidant parameters. Nitazoxanide treatment restored the histological architecture in rats along with the reduction of alveolar buds and downregulation of oxidative stress markers as well as inflammatory markers. Therefore, nitazoxanide can be utilized as a potential chemoprophylactic agent against mammary gland carcinoma induced by MNU.

Novel analogs of sulfasalazine as system xc- antiporter inhibitors: Insights from the molecular modeling studies.

System xc- (Sxc- ), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sxc- . However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood-brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure-activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sxc- antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sxc- inhibitory activity following in vitro Sxc- inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.

Circulating platelet aggregates damage endothelial cells in culture.

BACKGROUND: Presence of circulating endothelial cells (CECs) in systemic circulation may be an indicator of endothelial damage and/or denudation, and the body's response to repair and revascularization. Thus, we hypothesized that aggregated platelets (AgPlts) can disrupt/denude the endothelium and contribute to the presence of CEC and EC-derived particles (ECDP). METHODS: Endothelial cells were grown in glass tubes and tagged with/without 0.5 µm fluorescent beads. These glass tubes were connected to a mini-pump variable-flow system to study the effect of circulating AgPlts on the endothelium. ECs in glass tube were exposed to medium alone, nonaggregated platelets (NAgPlts), AgPlts, and 90 micron polystyrene beads at a flow rate of 20 mL/min for various intervals. Collected effluents were cultured for 72 h to analyze the growth potential of dislodged but intact ECs. Endothelial damage was assessed by real time polymerase chain reaction (RT-PCR) for inflammatory genes and Western blot analysis for von Willebrand factor. RESULTS AND CONCLUSION: No ECs and ECDP were observed in effluents collected after injecting medium alone and NAgPlts, whereas AgPlts and Polybeads drastically dislodged ECs, releasing ECs and ECDP in effluents as the time increased. Effluents collected when endothelial cell damage was seen showed increased presence of von Willebrand factor as compared to control effluents. Furthermore, we analyzed the presence of ECs and ECDPs in heart failure subjects, as well as animal plasma samples. Our study demonstrates that circulating AgPlts denude the endothelium and release ECs and ECDP. Direct mechanical disruption and shear stress caused by circulating AgPlts could be the underlying mechanism of the observed endothelium damage.

Emerging roles of system [Formula: see text] antiporter and its inhibition in CNS disorders.

System [Formula: see text] is an antiporter belonging to the hetero(di)meric amino acid transporter family. It is located on astrocytes as well as on blood-brain barrier within the CNS. It plays a pivotal role in free radical neutralization as well as neuronal signalling by regulating the glutathione production which occurs via the exchange of intracellular glutamate with extracellular cystine at 1:1 molar ratio. Understandably, it is a vital component responsible for the maintenance of neuronal homeostasis (e.g. redox state). Hence, it could be postulated that any perturbation in system [Formula: see text] function may contribute, directly or indirectly, to the pathophysiology of a variety of CNS disorders like Alzheimer's disease, schizophrenia, drug addiction, depression, multiple sclerosis, hypoglycemic neuronal cell death, glioma, and excitotoxicity, making system [Formula: see text] a promising target for treating CNS disorders. In recent times, recognizing the potential of this target, variety of inhibitors has been synthesized by modifying commercially available potent inhibitors including sulfasalazine, erastin, and sorafenib. Although, they have demonstrated efficacy, the in-depth data is still lacking to warrant their use for the treatment of aforementioned CNS disorders. In this review, we discuss the in-depth role of system [Formula: see text] transporter in maintaining normal physiology as well as in the pathophysiology of CNS diseases. Additionally, we have also listed some of the potent inhibitors of system [Formula: see text]. In conclusion, the critical role of system [Formula: see text] in multiple CNS disorders and advanced research on its inhibitors have promising future prospects for better management of the CNS ailments.

Serum Levels of Glycoproteins are Elevated in Patients with Ovarian Cancer.

Identification of reliable biomarkers for detection and staging of cancer and monitoring the outcome of anticancer therapy has been considered to be of high importance. We aimed to estimate the levels of serum glycoproteins, protein bound-hexose, protein bound hexosamine, protein bound fucose, protein bound sialic acid and protein bound carbohydrate in 32 ovarian cancer patients and compared them with the levels that found in 25 normal subjects. As compared to the normal subjects, all the four fractions of glycoproteins level were significantly elevated in ovarian cancer patients (p < 0.05). Chemotherapy in these patients significantly decreased the levels of serum glycoproteins (p < 0.05). Thus, high levels of serum glycoproteins in ovarian cancer patients could be due to abnormal protein glycosylation indicating malignant transformation of the cells.

Targeting heat shock protein 90 for malaria.

Heat shock protein 90 (Hsp90), an ATP-dependent molecular chaperone, is a highly conserved and ubiquitously expressed stress protein in eukaryotes. It is responsible for activation of various proteins involved in signal transduction, cell cycle control, hormone signaling, and transcription. Anomalous expression of this family can be associated with several disease states. Current article focuses on the novel use of Hsp90 inhibitors as antimalarial agents. The present armamentarium of antimalarial therapy is not proving itself as an adequate treatment to eradicate malaria completely. This inadequacy is mainly due to the increasing drug resistance rate in Plasmodium species. The parasite Plasmodium falciparum requires Hsp90 (Pfhsp90) for regulating its development. Analysis of PfHsp90 function suggests that it regulates parasite development during the frequent febrile episodes that are characteristic of malaria. This crucial role of Hsp90 in the growth and development of the parasite has attracted many researchers as a potential target for malaria and other infectious diseases. Currently there are about seven antimalarial and more than thirty anticancer Hsp90 inhibitors in various phases of drug development. Addition of alternatives with novel mechanism to the current treatment armoury may eventually help improve the outcomes of malaria. It is prudent to remain optimistic as the research in this field continues to evolve.

Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1α genes.

Based on the rapid hydrolysis of acetyl salicylic acid (ASA, Aspirin) to salicylic acid (SA), the ability of SA to form dihydroxy benzoic acid (DBA), and the latter's redox reactions to yield hydrogen peroxide (H(2)O(2)), we predicted that ASA may have the potential to induce Sirtuin1 (Sirt1) and its downstream effects. We observed that treatment of cultured liver cells with ASA resulted in the induction of Sirt1, peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α), and NAD(P)H quinone oxidoreductase 1 (Nqo1) genes. Paraoxonase 1 (PON1) and Aryl hydrocarbon receptor (AhR) siRNA transfections inhibited the induction of gene expressions by ASA suggesting the need for the acetyl ester hydrolysis and hydroxylation to DHBA. The latter also induced Sirt1, confirming the proposed pathway. As predicted, ASA and SA treatment resulted in the production of H(2)O(2), a known inducer of Sirt1 and confirmed in the current studies. More importantly, ASA treatment resulted in an increase in mitochondria as seen by tracking dyes. We suggest that DHBA, generated from ASA, via its oxidation/reduction reactions mediated by Nqo1 might be involved in the production of O(2)(-.) and H(2)O(2). As Sirt1 and PGC-1α profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases.

Moringa oleifera leaf extract prevents isoproterenol-induced myocardial damage in rats: evidence for an antioxidant, antiperoxidative, and cardioprotective intervention.

The present study evaluated cardioprotective effect of lyophilized hydroalcoholic extract of Moringa oleifera in the isoproterenol (ISP)-induced model of myocardial infarction. Wistar albino male rats were divided into three groups and orally fed saline once daily alone (sham) or with ISP (ISP control) or ISP with M. oleifera (200 mg/kg), respectively, for 1 month. On days 29 and 30 of administration, rats of the ISP control and M. oleifera-ISP groups were administered ISP (85 mg/kg, s.c.) at an interval of 24 hours. On day 31, hemodynamic parameters (mean arterial pressure [MAP], heart rate [HR], left ventricular end-diastolic pressure [LVEDP], and left ventricular peak positive [(+) LV dP/dt] and negative [(-) LV dP/dt] pressures were recorded. At the end of the experiment, the animals were sacrificed, and hearts were excised and processed for biochemical, histopathological, and ultrastructural studies. Chronic treatment with M. oleifera demonstrated mitigating effects on ISP-induced hemodynamic [HR, (+) LV dP/dt, (-) LV dP/dt, and LVEDP] perturbations. Chronic M. oleifera treatment resulted in significant favorable modulation of the biochemical enzymes (superoxide dismutase, catalase, glutathione peroxidase, lactate dehydrogenase, and creatine kinase-MB) but failed to demonstrate any significant effect on reduced glutathione compared to the ISP control group. Moringa treatment significantly prevented the rise in lipid peroxidation in myocardial tissue. Furthermore, M. oleifera also prevented the deleterious histopathological and ultrastructural perturbations caused by ISP. Based on the results of the present study, it can be concluded that M. oleifera extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, antiperoxidative, and myocardial preservative properties.

Pyruvate provides cardioprotection in the experimental model of myocardial ischemic reperfusion injury.

The present study was designed to evaluate the cardioprotective potential of pyruvate and to characterize the mechanism underlying the protection. Wistar albino rats were randomly divided into three groups. Two groups were administered saline orally (sham, ischemia-reperfusion (I-R) control group) and animals of third group received pyruvate (500 mg/kg) for 4 weeks. On the 29th day, animals of the I-R control and pyruvate treated groups underwent 45 min of occlusion of the left anterior descending (LAD) coronary artery and were thereafter reperfused for 60 min. In the I-R control group, a significant cardiac necrosis, depressed mean arterial pressure (MAP) and heart rate (HR), decline in myocardial antioxidant status and elevation in lipid peroxidation were observed as compared to sham control. Pyruvate treatment restored the myocardial antioxidant status and favorably modulated the altered MAP as compared to I-R control. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by pyruvate treatment. These beneficial cardioprotective effects translated into significant improvement in MAP. Histopathological examination and restored specific myocardial injury marker CK-MB isoenzyme activity further confirmed protective effects of pyruvate. In conclusion, our study has demonstrated that the beneficial effect of pyruvate likely results from improved MAP and suppression of oxidative stress.