Serum Lactate Dehydrogenase Activity Research Articles

Antifatigue Effect of Panax Notoginseng Leaves Fermented With Microorganisms: In-vitro and In-vivo Evaluation.

Fatigue is a common physiological phenomenon caused by many complicated factors. Excessive fatigue will lead to a series of uncomfortable reactions and damage body health. Panax notoginseng leaves (PNL) is a new resource food that good for soothing nerves, nourishing the heart, and strengthening the spleen. Microbial fermentation could increase the content of bio-ingredients and produce new active ingredients. However, the effect of fermented P. notoginseng leaves (FPNL) on antifatigue and the molecular mechanisms remain to be elucidated. Thus, in this study, we evaluated the antifatigue effect of co-fermented P. notoginseng leaves by Saccharomyces cerevisiae and Bacillus subtilis in-vitro and in-vivo, and its mechanism was further elucidated. The results showed that FPNL exhibited higher saponins, organic phenolic acids content, and antioxidant activity than PNL. FPNL improved ISO-induced H9c2 myocardial cell damage by alleviating apoptosis (modulating Bax and Bcl-2 protein expression) and reducing antioxidant activity in-vitro. Moreover, in-vivo experiment showed that FPNL significantly prolonged the weight-loading swimming time of mice. After gavaged FPNL, the levels of liver glycogen (LG) and serum lactate dehydrogenase (LDH) activity were increased in mice. In contrast, the levels of blood urea nitrogen (BUN), lactate acid, and malondialdehyde (MDA) were decreased. In summary, our results indicated that FPNL showed a good antifatigue effect in-vivo and in-vitro.

The Effect of Flammulina velutipes Polysaccharide on Immunization Analyzed by Intestinal Flora and Proteomics

Proteomics and intestinal flora were used to determine the mechanism of immune modulatory effects of Flammulina velutipes polysaccharide on immunosuppressed mice. The results showed that compared with the model group, F. velutipes polysaccharide could increase thymus and spleen indices and improve thymus tissue structure in mice; IL-2 and IL-4 contents were significantly increased and IL-6 and TNF-α contents were significantly decreased; serum acid phosphatase (ACP), lactate dehydrogenase (LDH) and total antioxidant capacity (T-AOC) activities were increased (P < 0.05); in the liver, superoxide dismutase (SOD) and catalase (CAT) activities were increased (P < 0.001), while malondialdehyde (MDA) content was decreased (P < 0.001). Proteomics discovered that F. velutipes polysaccharides may exert immune modulatory effects by participating in signaling pathways such as immune diseases, transport and catabolism, phagosomes and influenza A, regulating the immune-related proteins Transferrin receptor protein 1 (TFRC) and Radical S-adenosyl methionine domain-containing protein 2 (RSAD2), etc. Gut microbial studies showed that F. velutipes polysaccharides could increase the abundance of intestinal flora and improve the flora structure. Compared to the model group, the content of short-chain fatty acids (SCFAs) and the relative abundance of SCFA-producers Bacteroides and Alloprevotella were increased in the F. velutipes polysaccharide administration group, while Lachnospiraceae_NK4A136_group and f_Lachnospiraceae_Unclassified decreased in relative abundance. Thus, F. velutipes polysaccharide may play an immunomodulatory role by regulating the intestinal environment and improving the balance of flora.

Effect of one-time high load exercise on skeletal muscle injury in rats of different genders: oxidative stress and mitochondrial responses

To evaluate the impact of one-time high load exercise on skeletal muscle injury and analysis its mechanism in different genders. Twenty-four male and 24 female rats were divided randomly into four groups respectively: control, 0 h, 6 h, and 24 h after exercise. The activities of creatine kinase (CK), lactate dehydrogenase (LDH), and myohemoglobin (MYO) in serum, the expression level of oxidative stress markers, mitochondrial respiratory chain complex enzyme, and the apoptosis related protein in quadriceps were detected. The results showed that the activities of CK, LDH and MYO in serum increased immediately after exercise and restored faster in female rats. More obvious structural disorder and apoptosis in male rats were showed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were increased while catalase (CAT) and glutathione (GSH) were decreased in male rats. SOD, CAT and GSH were increased in female rats. Mitochondrial complex enzyme activity was decreased in males and increased in females. The skeletal muscle injury in both genders of rat could be induced by one-time high load exercise due to the mitochondrial respiratory enzyme dysfunction and oxidative stress, which was relatively mild and recovered quicker in female rats.

Bakır oksit nanopartikülleri ve Bakır sülfatın O. niloticus’da Serum Parametreleri ve Serum Enzim Aktiviteleri Üzerine Toksik Etkilerinin Karşılaştırılması

Today, human effects due to industrial development and population increase caused water ecosystems to be polluted by various pollutant such as heavy metals. Serum biochemical parameters are widely used in blood analysis and these parameters are suitable indicators for monitoring physiological changes in fish. Hence, the aim of present study to the effects of waterborne copper on serum glucose, total protein, albumin and triglyceride levels and serum cholinesterase (ChE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkalane phosphatase (ALP) and lactate dehydrogenase (LDH) activities of O. niloticus were determined after exposing the fish to 10, 50 and 100 µg/L copper applied as CuO nanoparticles (CuO NPs) and CuSO4 over 1, 7 and 15 days. &#x0D; No mortality was observed during the experiments. Serum glucose and albumin levels increased while serum total protein, cholesterol and triglyceride levels decreased compared to control at the end of the 15th day. There was also a decrease in serum ChE activity whereas serum AST, ALT, ALP and LDH activities increased. Overall, CuSO4 and CuO NPs had similar effects in serum parameters of O. niloticus.

Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study.

Background: There is a large amount of evidence that anti-angiogenic drugs are effective safe. However, few studies have evaluated the specific effects of anti-angiogenic drugs on myocardial enzyme injury biomarkers: aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether anti-angiogenic drugs serum AST, LDH, CK, and CK-MB activities of cancer patients treated with anti-angiogenic drugs.Methods: This study retrospectively analyzed 81 cancer patients. Patients who had used anti-angiogenic drugs were selected. Serum AST, LDH, CK, and CK-MB activities were measured before and after treatment with anti-angiogenic drugs for 3 weeks.Results: A total of 16 cancer types were analyzed. The distribution of the cancer types in the patients was mainly concentrated in lung, gastric, and colorectal cancers. The anti-angiogenic treatment markedly increased AST, LDH, CK, and CK-MB activities by 32.51, 7.29, 31.25, and 55.56%, respectively in serum.Conclusions: Our findings suggest that patients, who had used anti-angiogenic drugs were likely to have elevated AST, LDH, and CK, indicators of myocardial muscle injury. Use of anti-angiogenic drugs should not be assumed to be completely safe and without any cardiovascular risks.

Effects of different dietary canola and fish oil levels on overall performance, fatty acid profile, haemato‐biochemical responses, and digestibility of macronutrients of Caspian brown trout ( Salmo trutta caspius Kessler) fingerling

A 2-month feeding trial was undertaken to evaluate the effects of replacing dietary fish oil (FO) with canola oil (CO) at four levels of HF (100% fish oil), FF (70% fish oil + 30% canola oil), FV (50% fish oil + 50% canola oil), and HV (100% canola oil) on overall performance, haemato-biochemical responses, fatty acid composition and digestibility of Caspian brown trout, Salmo trutta caspius (Kessler) fingerlings. Fingerlings (N = 180, 4.6 ± 0.23 g) were randomly scattered to four various diet treatments. In fingerlings fed with FV diet a considerable increase in specific growth rate and weight gain were recorded (p < .05). No significant difference was observed in none of the macronutrients of the whole-body among the treatments (p > .05). The highest saturated fatty acids and the lowest monounsaturated fatty acids were recognized in the HF diet (p < .05). The lowest red blood cell was found in fingerlings fed HF diet (p < .05), but the white blood cell activity was not influenced in the groups (p > .05). The fingerlings that consumed the HF diet implied the highest aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase activities in serum than the other groups (p < .05). None of the whole-body compositions such as protein, lipid, ash, and moisture were affected by dietary treatments (p > .05). The lowest value of apparent digestibility of crude lipid (ADCCL) was observed in the HF group (p > .05). Overall, the data exhibited that elevating dietary canola oil up to 50% in Caspian brown trout fingerling resulted to improve growth efficiency and blood biochemistry.

Anti-fatigue effect of quercetin on enhancing muscle function and antioxidant capacity.

The aim of this study was to evaluate the anti-fatigue effect of quercetin in mice. Three-week-old male BALB/c mice, fed with/without 0.005% quercetin for 6weeks, were randomly divided into two experimental sets (loaded swimming and non-loading swimming tests). Our data indicated that dietary quercetin supplementation prolonged the exhaustive swimming time. In addition, lactic acid (LD) and blood urea nitrogen (BUN) levels, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in serum were significantly decreased, while the levels of non-esterified free fatty acids (NEFA) in serum and the content of liver glycogen and muscle glycogen were significantly enhanced in dietary quercetin supplementation group. Furthermore, dietary quercetin supplementation significantly enhanced the glutathione peroxidase (GPx) and catalase (CAT) activities in serum, liver and gastrocnemius muscle and enhanced the total superoxide dismutase (T-SOD) activity in gastrocnemius muscle, but decreased the malondialdehyde (MDA) content and reactive oxygen species (ROS) level. Meanwhile, dietary quercetin supplementation affected the mRNA expression of regulators factors involved in muscle damage and inflammation, glucose metabolism and gluconeogenesis, muscle mitochondrial fatty acid β-oxidation and antioxidant related genes. Together, our data confirm that dietary quercetin supplementation can promote anti-fatigue capacity by promoting the antioxidant capacity and glycogen storage, as well as enhancing muscle function. PRACTICAL APPLICATIONS: Quercetin is a natural polyphenolic flavonoid substance. Here we confirm that quercetin has anti-fatigue activity. Our study indicates that quercetin may be used as natural anti-fatigue functional food or drugs.

Mesenchymal stem cells seeded onto nanofiber scaffold for myocardial regeneration

ABSTRACT Cardiac disease is the leading cause of mortality and disability worldwide. We investigated the role of undifferentiated adipose tissue-derived mesenchymal stem cells (ADMSC) alone and ADMSC seeded onto the electro-spun nanofibers (NF) for reconstructing damaged cardiac tissue in isoprenaline-induced myocardial infarction (MI) in rats. ADMSC were sorted by morphological appearance and by detection of cluster of differentiation (CD) surface antigens. The therapeutic potential of ADMSC for treating MI was evaluated by electrocardiogram (ECG), biochemical analysis, molecular genetic analysis and histological examination. Treatment of MI-challenged rats with ADMSC improved ECG findings, which were corroborated by significant decreases in serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzyme activities together with reduced serum troponin T (cTnT) and connexin 43 (Cx43) levels. MI model rats treated with ADMSC exhibited a significant increase in serum alpha sarcomeric actin (Actn) and GATA binding protein 4 (GATA4), and NK2 homeobox 5 (NKX2.5) gene expression was decreased following treatment with ADMSC. ADMSC also ameliorated damage to cardiac tissue. The effects of ADMSC seeded onto NF were superior to those of ADMSC alone. ADMSC may be useful for mitigation of MI.

ОЦЕНКА ВЛИЯНИЯ ОЖИРЕНИЯ НА ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ У СОБАК

Dogs’ obesity in is a common pathology and is associated with genetic factors, feeding, housing conditions, physical inactivity. Many pathogenesis aspects of obesity development of small domestic animals are poorly studied, in particular, the development of dysfunction of the cardiovascular system is an insufficiently explored issue. The aim of this study was to study clinical, electrocardiographic, echocardiographic and biochemical parameters of blood serum of obese dogs. The objects of the study were Dachshund dogs with obesity (n = 12) and clinically healthy animals (n = 16). All animals went through a complex clinical examination, electrocardiographic, echocardiographic and laboratory studies. Parametric and nonparametric methods of statistical analysis were used in the study. It was found that dogs’ obesity is characterized by a significant increase of the respiratory rate at rest and during sleep, pulse rate, systolic, diastolic and mean arterial blood pressure. It was shown that in case of dogs’ obesity, there is a slight increase of the end-diastolic size and thickness of the free wall of the left ventricle, a shortening of the PQ interval, and voltage decrease of P, R, T deflections on electrocardiograms. There were no violations of contractility and systolic function of the left ventricular myocardium of obese dogs. It was found that the activity of alkaline phosphatase, alanine and aspartic aminotransferases, the concentration of cholesterol, triglycerides, total protein, malondialdehyde and ceruloplasmin significantly increased in blood serum of obese dogs. Dogs’ obesity does not form dogs’ syndrome of cytolysis of cardiomyocytes, as evidenced by unchanged serum activity of lactate dehydrogenase, creatine phosphokinase and cardiac troponin concentration.

Serum prolactin level and lactate dehydrogenase activity in patients with epileptic and nonepileptic seizures: A cross-sectional study.

It is important to diagnose epilepsy in a timely and accurate manner, and also to distinguish it from non-epileptic conditions. The present study was aimed at determining postictal serum prolactin levels and lactate dehydrogenase (LDH) activities in patients with new-onset seizure admitted to the emergency department in order to assess whether they could be used in the differentiation of epileptic seizure (ES) from nonepileptic seizure (NES).Eighty-five patients were included prospectively in this study. Patients were divided into 2 groups with respect to epilepsy diagnosis, and the final groups were comprised of 36 patients with ES and 49 patients with NES. Blood samples were obtained within 1 hour of seizure.No significant differences between groups were observed in prolactin levels and in the percentage of patients with abnormal prolactin level (P = .569 and .239, respectively). The median LDH activity was significantly higher in those with ES compared with those with NES (P = .031). The percentage of patients with elevated LDH levels was similar between 2 groups (P = .286).This was the first study to examine LDH activities in terms of its role in differentiation of seizure origin in the postictal period in patients hospitalized with seizure. Our study demonstrated that serum LDH activities within 1 hour after the seizure appear to be increased in patients with ES compared with those with NES, suggesting the potential role of LDH activities as a diagnostic tool in distinction of seizure types. Our study supports the hypothesis that LDH-antagonists may have a role in the management of seizure and epilepsy.

The phenotypic and haemato-biochemical appraisal of tropical theileriosis in newborn calves

Tropical theileriosis is one of the major causes of newborn calves mortality. Observation of clinical manifestations is important while making the presumptive/tentative diagnosis of tropical theileriosis in newborn calves. The phenotypic and haemato-biochemical appraisals of tropical theileriosis could be of great help to make a holistic therapeutic plan for diseased newborn calves. Therefore, the present study aimed to evaluate the haemato-biochemical and phenotypic diagnostic markers of tropical theileriosis in newborn calves. A total of 43 newborn calves naturally infected with Theileria annulata and 16 age-matched healthy calves were enrolled. The percentage distribution of clinical markers was generalized lymph nodes enlargement (100%), pyrexia (97.67%), respiratory distress (95.34%), tick infestation (90.69%), anorexia (88.37%), pica (81.39%), pallor mucous membrane (67.44%), hyperlacrimation (58.13%) and exophthalmia (30.22%). Haemograms including TEC, Hb and HCT were found to be significantly (P ≤ 0.001) lowered in diseased calves. Remarkable alterations in the leukogram panels were not observed. Serum glucose, total protein, albumin and globulin concentrations of calves with theileriosis were significantly (P ≤ 0.001) lower than healthy ones, whereas triglycerides and total cholesterol levels of diseased calves were significantly (P ≤ 0.001) higher. Significantly (P ≤ 0.001) elevated activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzymes were observed in diseased calves. An evaluation of clinical phenotypes could be helpful to initiate quick treatment of diseased calves in field conditions and save the lives of sick calves of economically poor farmers. Altered haemato-biochemical panels to be appraised by veterinary clinicians while making a therapeutic plan of tropical theileriosis.

Effects of Dietary Protein and Lipid Levels on Growth, Body Composition, Blood Biochemistry, Antioxidant Capacity and Ammonia Excretion of European Grayling (Thymallus thymallus)

This study evaluated growth, body composition, antioxidant capacity, innate immunity and ammonia excretion of European grayling (Thymallus thymallus) fed diets containing different protein and lipid contents. Six diets were produced to contain 30, 40, or 50% protein and 10 or 20% lipid. Juvenile fish averaging 25.2 ± 0.28 g were stocked into eighteen 450-L circular tanks in a recirculating aquaculture system (RAS) and fed the test diets to satiation twice daily for 12 weeks. Fish weight gain (WG) was enhanced (P &amp;lt; 0.05) as dietary protein increased from 30% (229% WG) to 40% (262% WG) and plateaued thereafter. Enhancing protein and lipid content of diet led to reduced feed intake. Also, feed efficiency was improved by increasing dietary protein (by 40.8%) and lipid (by 16.5%) levels. An interaction of protein and lipid was found on whole-body lipid, and muscle lipid content increased as dietary lipid level increased. Muscle arachidonic acid (ARA), eicosapentaenoic acid (EPA, 20:5n-3) and total n-6 long-chain polyunsaturated fatty acids (LC-PUFA) contents enhanced by increasing dietary protein level. Moreover, increasing fat content of diet led to enhanced muscle linoleic acid, linolenic acid, total monounsaturated fatty acids (MUFA), total n-6, ratio of docosahexaenoic acid (DHA, 22:6n-3) to EPA and n-6/n-3. However, EPA, DHA, total n-6 LC-PUFA, total n-3, total n-3 LC-PUFA, and EPA/ARA ratio decreased at higher dietary lipid level. Serum triglyceride (TG) level and lactate dehydrogenase (LDH) activity decreased as dietary protein level increased. Increasing fat content of diet led to enhanced serum TG, cholesterol and glucose concentrations and reduced alanine aminotransferase, aspartate amino transferase and LDH activities. Serum malondialdehyde concentration was enhanced by increasing both dietary protein and lipid. Furthermore, serum myeloperoxidase activity was enhanced at higher dietary lipid level. Water ammonium nitrogen (NH4+-N) concentration was measured after 5 and 24 h of last feeding, and the results indicated the reduction of ammonia excretion as dietary lipid content increased. These findings suggest that 40% dietary protein can support optimal growth of juvenile European grayling reared in RAS and increasing lipid content from 10 to 20% can improve feed utilization and reduce ammonia excretion to the rearing water.

Pomegranate Polyphenols Attenuate Inflammation and Hepatic Damage in Tumor-Bearing Mice: Crucial Role of NF-κB and the Nrf2/GSH Axis

It has been widely reported that cancer, along with its treatment regimens, cause severe toxicity in the host. A suitable agent having chemopreventive properties as well as capabilities of ameliorating tumor- and drug-induced toxicities is of imminent need. Pomegranate has been projected as an excellent anti-tumor, anti-inflammatory and anti-oxidant agent. In this study, for the first time, we delineated the exact signaling cascade by which dietary supplementation of pomegranate fruit extract (PFE) protects tumor-bearing mice from tumor-induced hepatotoxicity. Increased activities of serum Alanine transaminase, Aspartate transaminase, Lactate dehydrogenase and Alkaline phosphatase, as well as histological studies confirmed the establishment of a state of hepatic dysfunction in tumor-bearers. Further investigations revealed that increased hepatic reactive oxygen species content and glutathione depletion-initiated apoptosis in these hepatocytes as we observed an alteration in the apoptotic proteins. PFE supplementation in tumor-bearing mice, on the other hand, differentially modulated redox-sensitive transcription factors Nrf2 and NF-κB, ultimately decreasing tumor-induced hepatic oxidative damage and cell death. siRNA-mediated inhibition of Nrf2 and NF-κB completely abolished the hepato-protective activities of PFE while pre-treatment of tumor-conditioned hepatocytes with N-acetyl cysteine augmented the cyto-protective properties of PFE. The present study clearly identified Nrf2/NF-κB/glutathione axis as the key factor behind the hepatoprotective potential of PFE. These findings would add to the existing knowledge about cancer chemoprevention by dietary polyphenols and might lead to the application of pomegranate polyphenols as supplement to escalate the effectiveness of cancer therapy by protecting normal cells from cancer related toxicities.

Щодо окремих клініко-параклінічних маркерів сепсис-індукованої міокардіальної дисфункції в новонароджених

The problem of neonatal sepsis continues to be one of the leading places in neonatal practice. The issues of early diagnostics of cardiovascular disorders in neonates with sepsis by means of up-to-date methods of examination remain relevant. They can be used as screening methods with the purpose to verify possible development of cardiovascular dysfunction. Purpose — to study the meaning of certain clinical and paraclinical markers of myocardial dysfunction in neonates with sepsis. Materials and methods. In order to realize the objective we have observed 69 neonates with signs of generalized infectious-inflammatory process. Group I (32 patients — 46,4%) included neonates with the term of gestation 37–42 weeks, group II included 37 preterm neonates (53,6%) with the term of gestation under 36 week inclusive. Results. It was found that in mothers who gave birth prematurely, compared to mothers of newborns of group I, premature rupture of membranes occurred more often, but 1.5 times less often — indications of infectious diseases of the genitourinary system of the pregnant woman. Generalized infectious-inflammatory process during the neonatal period of term infants is accompanied by electrocardiographic signs of left ventricular overload associated with female sex (r=0,30), delivery by cesarean section (r=0,27), and assessment of neonatal condition by a 5=minute Apgar score (r=-0,33). Conclusions. Increased values of lactate dehydrogenase activity in the blood serum of both term and preterm neonates are associated with left ventricular over-load in the term ones, and right ventricular overload in the preterm infants. Changes found in electrophysiological heart activity promote the necessity of a routine use of electrocardiography in neonates with signs of septic process. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: neonatal sepsis; myocardial dysfunction.

Serum lactate dehydrogenase activities as systems biomarkers for 48 types of human diseases

Most human diseases are systems diseases, and systems biomarkers are better fitted for diagnostic, prognostic, and treatment monitoring purposes. To search for systems biomarker candidates, lactate dehydrogenase (LDH), a housekeeping protein expressed in all living cells, was investigated. To this end, we analyzed the serum LDH activities from 172,933 patients with 48 clinically defined diseases and 9528 healthy individuals. Based on the median values, we found that 46 out of 48 diseases, leading by acute myocardial infarction, had significantly increased (p < 0.001), whereas gout and cerebral ischemia had significantly decreased (p < 0.001) serum LDH activities compared to the healthy control. Remarkably, hepatic encephalopathy and lung fibrosis had the highest AUCs (0.89, 0.80), sensitivities (0.73, 0.56), and specificities (0.90, 0.91) among 48 human diseases. Statistical analysis revealed that over-downregulation of serum LDH activities was associated with blood-related cancers and diseases. LDH activities were potential systems biomarker candidates (AUCs > 0.8) for hepatic encephalopathy and lung fibrosis.

Electroacupuncture Pretreatment Mitigates Myocardial Ischemia/Reperfusion Injury via XBP1/GRP78/Akt Pathway.

Myocardial ischemia/reperfusion injury is a common clinical problem and can result in severe cardiac dysfunction. Previous studies have demonstrated the protection of electroacupuncture against myocardial ischemia/reperfusion injury. However, the role of X-box binding protein I (XBP1) signaling pathway in the protection of electroacupuncture was still elusive. Thus, we designed this study and demonstrated that electroacupuncture significantly improved cardiac function during myocardial ischemia/reperfusion injury and reduced cardiac infarct size. Electroacupuncture treatment further inhibited cardiac injury manifested by the decrease of the activities of serum lactate dehydrogenase and creatine kinase-MB. The results also revealed that electroacupuncture elevated the expressions of XBP1, glucose-regulated protein 78 (GRP78), Akt, and Bcl-2 and decreased the Bax and cleaved Caspase 3 expressions. By using the inhibitor of XBP1 in vitro, the results revealed that suppression of XBP1 expression could markedly increase the activities of lactate dehydrogenase and creatine kinase-MB and cell apoptosis, thus exacerbating stimulated ischemia/reperfusion-induced H9c2 cell injury. Compared with stimulated ischemia/reperfusion group, inhibition of XBP1 inhibited the downstream GRP78 and Akt expressions during stimulated ischemia/reperfusion injury. Collectively, our data demonstrated that electroacupuncture treatment activated XBP1/GRP78/Akt signaling to protect hearts from myocardial ischemia/reperfusion injury. These findings revealed the underlying mechanisms of electroacupuncture protection against myocardial ischemia/reperfusion injury and may provide novel therapeutic targets for the clinical treatment of myocardial ischemia/reperfusion injury.

Potentiation of flutamide-induced hepatotoxicity in mice by Xian-Ling-Gu-Bao through induction of CYP1A2

Ethnopharmacological relevanceXian-Ling-Gu-Bao (XLGB) Fufang is herbal formula widely used to treat osteoporosis and other bone disorders. Because of its commonality in the clinical use, there is a safety concern over the use of XLGB combined with other androgen deprivation therapy (ADT) drugs such as flutamide (FLU) that is associated with reduced bone density. To date, there have been no evaluations on the side effects of the drug-drug interaction between XLGB and FLU. Aim of the studyThe present study was designed to investigate the hepatotoxicity in the context of the combined treatment of XLGB and FLU in a mouse model, and to determine whether the metabolic activation of FLU through induction of CYP1A2 plays a role in the increased hepatoxicity caused by the combination of XLGB and FLU. Materials and methodsC57 mice were administered with either XLGB (6,160 mg/kg), FLU (300 mg/kg), or with the combination of the two drugs. Animals were treated with XLGB for 5 days before the combined administration of XLGB and FLU for another 4 days. The serum of mice from single or the combined administration groups was collected for biochemical analysis. The mouse liver was collected to examine liver morphological changes, evaluate liver coefficient, as well as determine the mRNA expression of P450 isozymes (Cyp1a2, Cyp3a11 and Cyp2c37). For metabolism analysis, mice were treated with XLGB, FLU, or the combination of XLGB and FLU for 24 h. The urine samples were collected for the analysis of FLU-NAC conjugate by UPLC-Q-Orbitrap MS. The liver microsomes were prepared from fresh livers to determine the activity of metabolizing enzyme CYP1A2. ResultsThe combined treatment of XLGB and FLU caused loss of mice body weight and elicited significant liver toxicity as evidenced by an increased liver coefficient and serum lactate dehydrogenase (LDH) activity as well as pathological changes of fatty lesion of liver tissue. FLU increased hepatic expression of Cyp1a2 mRNA that was further elevated in the liver of mice when administered with both FLU and XLGB. Treatment of FLU resulted in an increase in the expression of Cyp3a11 mRNA that was negated when mice were co-treated with FLU and XLGB. No significant difference in Cyp2c37 mRNA expression was observed among the different treatment groups as compared to the control. Analysis of metabolic activity showed that the combined administration caused a synergic effect in elevating the activity of the CYP1A2 enzyme. Mass spectrometry analysis identified the presence of FLU reactive metabolite derived FLU-NAC conjugate in the urine of mice treated with FLU. Strikingly, about a two-fold increase of the FLU-NAC conjugate was detected when treated with both FLU and XLGB, indicating an elevated amount of toxic metabolite produced from FLU in the present of XLGB. ConclusionFLU and XLGB co-treatment potentiated FLU-induced hepatoxicity. This increased hepatoxicity was mediated through the induction of CYP1A2 activity which in turn enhanced bioactivation of FLU leading to over production of FLU-NAC conjugate and oxidative stress. These results offer warnings about serious side effects of the FLU-XLGB interaction in the clinical practice.

Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats.

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

Structure and signifi cance of cytogenetic abnormalities in patients with multiple myeloma

Introduction. Cytogenetic and genomic traits of tumour cells are considered the key mediating factors in multiple myeloma (MM). Selected chromosomal abnormalities are prognostic of therapeutic response and patient survival in MM.Aim — to assess of the diversity and rate of chromosomal abnormalities in MM patients and their association with the disease course.Materials and methods. The study enrolled 134 MM patients with pre-treatment bone marrow FISH assay screening for chromosomal abnormalities: t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), hyperdiploidy, del13q14/-13, del17p13/TP53, amp1q21, t(8q24)/cMYC. The studied criteria at the MM onset were: hemogram, lactate dehydrogenase (LDH) activity, calcium, β2-microglobulin and creatinine concentrations, punctate cytology, bone marrow trephine biopsy and/or soft tissue biopsy histology, bone X-ray, immunochemical variant of MM, disease staging. A median follow-up was 20 months (3.2–77.4).Results. The primary chromosomal abnormality rate was 82.9 %, among them t(14q32)/IGH — 29.1 %, multiple trisomies — 46.3 % and their combination — 7.5 %. The rates of particular t(14q32)/IGH): t(11;14) — 16.4 %, t(4;14) — 12.7 %, t(14;16) and t(14;20) — 3.7 and 2.2 %, respectively. The secondary chromosomal abnormality rate was 69.4 %, among them del13q14/-13 — 40.3 %, amp1q21 — 39.6 %, t(8q24)/cMYC — 17.2 %, del17p13/TP53 — 12.7 %, del1p32 — 2.2 %. Analyses of the primary–secondary abnormality combinations showed that del13q14/-13 is more frequently combined with t(4;14) and less frequently with trisomies (p &lt; 0.05). Amp1q21 occurs more frequently with t(4;14) and less — with t(11;14) (p&lt;0.05). Patients with t(4;14) more frequently (p &lt; 0.05) had anemia at a hemoglobin level&lt;100 g/L, and the presence of amp1q21 and del17p13/TP53-enhanced serum LDH activity (p &lt; 0.05). Abnormality t(8q24)/cMYC more often co-occurred with higher serum β2-microglobulin concentrations (p &lt; 0.05). A three-year overall survival (OS) in del17p13/TP53-positive patients was 35.5 vs. 71.3 % in the negative (p = 0.002) and 50.8 vs. 67 % — in t(8q24)/cMYC-positive and negative patients, respectively (p = 0.001). Patients without amp1q21, with one, with two or more additional 1q21 copies had a five-year OS 79.4, 67.3 and 20.9 %, respectively (p = 0.0016), and a two-year progression-free survival (PFS) 83, 50 and 0 %, respectively (p = 0.005).Conclusion. We establish a negative impact of del17p13/TP53 and t(8q24)/cMYC on patients’ OS in MM, as well as unfavourable effect of amp1q21 on OS and PFS in the presence of two or more additional copies of 1q21 loci.

Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways.

Simple SummaryThe use of date palm pollen ethanolic extract (DPPE) is a conventional approach in improving the side-effects induced by Doxorubicin (DOX).DPPE mitigated DOX-induced body and heart weight changes and ameliorated DOX-induced elevated cardiac injury markers. In addition, serum cardiac troponin I concentrations (cTnI), troponin T (cTnT), and N-terminal NBP and cytosolic (Ca+2) were amplified by alleviating the inflammatory and oxidative injury markers and decreasing histopathological lesions severity. DPPE decreased DOX-induced heart injuries by mitigating inflammation, fibrosis, and apoptosis through its antioxidant effect. To reduce DOX-induced oxidative stress injuries and other detrimental effects, a combined treatment of DPPE is advocated.Doxorubicin (DOX) has a potent antineoplastic efficacy and is considered a cornerstone of chemotherapy. However, it causes several dose-dependent cardiotoxic results, which has substantially restricted its clinical application. This study was intended to explore the potential ameliorative effect of date palm pollen ethanolic extract (DPPE) against DOX-induced cardiotoxicity and the mechanisms underlying it. Forty male Wistar albino rats were equally allocated into Control (CTR), DPPE (500 mg/kg bw for 4 weeks), DOX (2.5 mg/kg bw, intraperitoneally six times over 2 weeks), and DPPE + DOX-treated groups. Pre-coadministration of DPPE with DOX partially ameliorated DOX-induced cardiotoxicity as DPPE improved DOX-induced body and heart weight changes and mitigated the elevated cardiac injury markers activities of serum aminotransferases, lactate dehydrogenase, creatine kinase, and creatine kinase-cardiac type isoenzyme. Additionally, the concentration of serum cardiac troponin I (cTnI), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), and cytosolic calcium (Ca+2) were amplified. DPPE also alleviated nitrosative status (nitric oxide) in DOX-treated animals, lipid peroxidation and antioxidant molecules as glutathione content, and glutathione peroxidase, catalase, and superoxide dismutase activities and inflammatory markers levels; NF-κB p65, TNF-α, IL-1β, and IL-6. As well, it ameliorated the severity of histopathological lesions, histomorphometric alteration and improved the immune-staining of the pro-fibrotic (TGF-β1), pro-apoptotic (caspase-3 and Bax), and anti-apoptotic (Bcl-2) proteins in cardiac tissues. Collectively, pre-coadministration of DPPE partially mitigated DOX-induced cardiac injuries via its antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic potential.