Plasma LDH Activity Research Articles

Predictive factors associated with short-term mortality in cats with feline infectious peritonitis treated with remdesivir or GS-441524 or both.

Although most cats with feline infectious peritonitis (FIP) respond to treatment with remdesivir or GS-441524 or both with uneventful clinical courses, some die despite treatment. Identify predictive factors associated with short-term mortality in cats with FIP treated with IV remdesivir or PO GS-441524 or both. A total of 108 client-owned cats with FIP. Retrospective multicenter study using data collected from medical records. Factors associated with short-term mortality, defined as death within 84 days, were identified. Univariate analysis a t-test, Mann-Whitney U test, or Fisher's exact test and multivariate logistic regression were performed to assess patient characteristics and clinicopathological variables between survivors and nonsurvivors. The short-term mortality rate was 12.0% (95% confidence interval [CI], 6.6%-19.7%). Univariate analysis identified plasma lactate dehydrogenase activity (LDH; P < .001) and bilirubin concentration (P = .001) as being significantly increased in nonsurvivors, whereas concentrations of albumin (P = .003), total protein (P = .03), sodium (P = .005), and potassium (P = .005) were significantly lower. Additionally, nonsurvivors were significantly less likely to be febrile (≥39.4°C; P = .006). Of these variables, only plasma LDH activity ≥323 U/L, a cut-point determined by receiver operating characteristic curve analysis, was significantly associated with short-term mortality by multivariate analysis (odds ratio, 15.30; 95% CI, 1.18-198.00; P = .04). Increased plasma LDH activity might be useful for predicting short-term mortality, guiding monitoring, and establishing prognosis in cats with FIP.

LncRNA-6395 promotes myocardial ischemia-reperfusion injury in mice through increasing p53 pathway.

Myocardial ischemia-reperfusion (I/R) injury is a pathological process characterized by cardiomyocyte apoptosis, which leads to cardiac dysfunction. Increasing evidence shows that abnormal expression of long noncoding RNAs (lncRNAs) plays a crucial role in cardiovascular diseases. In this study we investigated the role of lncRNAs in myocardial I/R injury. Myocardial I/R injury was induced in mice by ligating left anterior descending coronary artery for 45 min followed by reperfusion for 24 h. We showed that lncRNA KnowTID_00006395, termed lncRNA-6395 was significantly upregulated in the infarct area of mouse hearts following I/R injury as well as in H2O2-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Overexpression of lncRNA-6395 led to cell apoptosis and the expression change of apoptosis-related proteins in NMVCs, whereas knockdown of lncRNA-6395 attenuated H2O2-induced cell apoptosis. LncRNA-6395 knockout mice (lncRNA-6395+/-) displayed improved cardiac function, decreased plasma LDH activity and infarct size following I/R injury. We demonstrated that lncRNA-6395 directly bound to p53, and increased the abundance of p53 protein through inhibiting ubiquitination-mediated p53 degradation and thereby facilitated p53 translocation to the nucleus. More importantly, overexpression of p53 canceled the inhibitory effects of lncRNA-6395 knockdown on cardiomyocyte apoptosis, whereas knockdown of p53 counteracted the apoptotic effects of lncRNA-6395 in cardiomyocytes. Taken together, lncRNA-6395 as an endogenous pro-apoptotic factor, regulates cardiomyocyte apoptosis and myocardial I/R injury by inhibiting degradation and promoting sub-cellular translocation of p53.

Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk.

Many studies have shown that crosstalk exists between apoptosis and autophagy, despite differences in mechanisms between these processes. Paeonol, a major phenolic compound isolated from Moutan Cortex Radicis, the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), is widely used in traditional Chinese medicine as an antipyretic, analgesic and anti-inflammatory agent. In this study, we investigated the detailed molecular mechanisms of the crosstalk between apoptosis and autophagy underlying the cardioprotective effects of paeonol in rats subjected to myocardial ischemia/reperfusion (I/R) injury. Myocardial I/R injury was induced by occlusion of the left anterior descending coronary artery (LAD) for 1 h followed by 3 h of reperfusion. Paeonol was intravenously administered 15 min before LAD ligation. We found that paeonol significantly improved cardiac function after myocardial I/R injury and significantly decreased myocardial I/R-induced arrhythmia and mortality. Paeonol also significantly decreased myocardial infarction and plasma LDH activity and Troponin-I levels in carotid blood after I/R. Compared with vehicle treatment, paeonol significantly upregulated Bcl-2 protein expression and significantly downregulated the cleaved forms of caspase-8, caspase-9, caspase-3 and PARP protein expression in the I/R injured myocardium. Myocardial I/R-induced autophagy, including the increase of Beclin-1, p62, LC3-I, and LC3-II protein expression in the myocardium was significantly reversed by paeonol treatment. Paeonol also significantly increased the Bcl-2/Bax and Bcl-2/Beclin-1 ratios in the myocardium after I/R injury. The cardioprotective role of paeonol during I/R injury may be due to its mediation of crosstalk between apoptotic and autophagic signaling pathways, which inhibits apoptosis and autophagic cell death.

Enrichment of alpha-linolenic acid in rodent diet reduced oxidative stress and inflammation during myocardial infarction

Myocardial infarction (MI) is an irreversible event caused by cardiac ischemia and may be fatal. Studies reported that increased intake of n-3 polyunsaturated fatty acids (PUFA) namely, eicosapentaenoic acid and docosahexaenoic acid reduce the risk of cardiovascular disease and lower the incidence of MI. Nonetheless, the cardioprotective effect of plant n-3-PUFA such as α-linolenic acid (ALA) in the diet is not conclusive. In this study, Sprague Dawley rats were supplemented with isocaloric diets enriched with ALA rich flaxseed (FS) and flaxseed oil (FSO), and normal chow (Control) for 4 weeks. MI was induced by isoproterenol (ISO) injection. Results showed that all ALA-enriched diets displayed cardioprotection against MI. The heart to body weight ratio, plasma LDH activity and plasma cTnI were reduced compared to ISO and was prominent in FS diet. ALA and EPA were up-regulated in both tissues and plasma by ALA-diets compared to Control and remained higher than ISO groups. Notably, LOX-mediated HETEs decreased whereas LOX-mediated HDHAs were elevated in both tissues and plasma of ALA-enriched diets compared to ISO. In addition, non-enzymatic oxidized products from arachidonic acid including 15-F2t-IsoP were reduced in both tissues and plasma of MI rats supplemented with ALA-enriched diets while those from n-3 PUFAs including F4-NeuroPs, PhytoPs and PhytoFs were elevated compared to control. ALA-enriched diets particularly flaxseed reduced gene expressions of inflammatory cytokines namely IL-1β, IL-6 and TNFα and prevented the down regulation of antioxidant catalase in the heart tissues. In conclusion ALA-enriched diets potentially exerted cardioprotection through the regulation of anti-inflammatory and anti-oxidative mediators from n-3 PUFA autooxidation.

Salvia officinalis mitigates uterus and liver damages induced by an estrogen deficiency in ovariectomized rats.

The present study evaluated the antioxidant activity of Salvia officinalis (sage) and its protective effect on estrogen deficiency in ovariectomized rats. Female Wistar rats were treated during either 15 or 30days as follows: group C: negative controls, group S: positive controls treated with sage leaves, ovariectomized rats (group OVX) and ovariectomized rats receiving either sage (OVX-S) or hormonal (Group OVX-E) treatments, respectively. After 15 and 30days of treatments, OVX rats showed a gain in body weight and an increase of absolute and relative liver weights. Meanwhile, absolute and relative uterus weights were decreased. Moreover, ovariectomy altered plasma transaminases' activities, lipid profile, and disrupted the redox status of liver and uterine tissues. It affected also the reproductive tract by decreasing the uterus glycogen content and plasma LDH activity. Supplementation of sage via the diet reduced weight gain and oxidative stress resulting from estrogen deficiency. PRACTICAL APPLICATIONS: During menopause, sexual hormone deficiency, especially estrogen, causes several morphological and physiological disturbances in liver and uterus tissues. In fact, the body weight gain and disturbances of redox status in liver and uterus were the main health problems detected after menopause. Sage leaves, used as medicinal plant, exerted its beneficial effects in the management of menopause disorders. As an important source of antioxidants, sage leaves could prevent obesity and oxidative damage in the liver and uterus resulting from estrogen deficiency.

Anti-oxidant and hepatoprotective effects of Salvia officinalis essential oil against vanadium-induced oxidative stress and histological changes in the rat liver.

The present study was designed to evaluate the protective effects of Salvia officinalis essential oil (SOEO) against vanadium-induced hepatotoxicity in Wistar rats. Animals were divided into three groups: the first group served as the control (C), where rats received daily 0.5mL of saline solution (0.9%) given by intraperitoneal (i.p.) way. Rats in the second group (V) received daily by i.p. way 5mg/kg BW of NH4VO3 (V). Rats in the third group (SV) received daily V (5mg/kg BW) by i.p. way and SOEO (15mg/kg BW) by gavage. Animals were sacrificed after 4 or 10days of treatment. Administration of V increased plasma ALT, AST, ALP, and LDH activities, and cholesterol, bilirubin, triglyceride, and NO levels in rats and reduced anti-oxidant enzyme activities in the liver. Treatment with SOEO significantly attenuated these changes. Moreover, the histopathological changes and the overexpression of Hsp72/73 proteins induced by V were significantly improved by SOEO. Therefore, our results suggested that SOEO could protect against V-induced oxidative damage in rat livers. The hepatoprotective effect of SOEO might be attributed to its modulation of detoxification enzymes and/or to its anti-oxidant and free radical scavenging effects.

Catalpol counteracts the pathology in a mouse model of Duchenne muscular dystrophy by inhibiting the TGF-β1/TAK1 signaling pathway.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by a mutation in the gene encoding the dystrophin protein. Catalpol is an iridoid glycoside found in Chinese herbs with anti-inflammatory, anti-oxidant, anti-apoptotic, and hypoglycemic activities that can protect against muscle wasting. In the present study we investigated the effects of catalpol on DMD. Aged Dystrophin-deficient (mdx) mice (12 months old) were treated with catalpol (100, 200 mg·kg-1·d-1, ig) for 6 weeks. At the end of the experiment, the mice were sacrificed, and gastrocnemius (GAS), tibialis anterior (TA), extensor digitorum longus (EDL), soleus (SOL) muscles were collected. We found that catalpol administration dose-dependently increased stride length and decreased stride width in Gait test. Wire grip test showed that the time of wire grip and grip strength were increased. We found that catalpol administration dose-dependently alleviated skeletal muscle damage, evidenced by reduced plasma CK and LDH activity as well as increased the weight of skeletal muscles. Catalpol administration had no effect on dystrophin expression, but exerted anti-inflammatory effects. Furthermore, catalpol administration dose-dependently decreased tibialis anterior (TA) muscle fibrosis, and inhibited the expression of TGF-β1, TAK1 and α-SMA. In primary myoblasts from mdx mice, knockdown of TAK1 abolished the inhibitory effects of catalpol on the expression levels of TGF-β1 and α-SMA. In conclusion, catalpol can restore skeletal muscle strength and alleviate skeletal muscle damage in aged mdx mice, thus may provide a novel therapy for DMD. Catalpol attenuates muscle fibrosis by inhibiting the TGF-β1/TAK1 signaling pathway.

An antioxidant activity of Cinnamonum tamala improves histopathological alterations and biochemical parameters in alloxan induced diabetic rats

Background: Diabetic mellitus is a multifactorial disorder associated with its devastating consequences has assumed epidemic proportion. Diabetes mellitus (DM) is a global health problem and the incidence of DM is increasing at alarming rate all over the world. Many Indian medicinal plants have been reported to possess potential antidiabetic activity and could play important role in the management of diabetes with less adverse effects.&#x0D; Aims and Objectives: The main objective of this study was to focus on the anti-diabetic activity of Cinnamomum tamala, with special reference to its curative and protective role in alloxan induced diabetic rats. Attempts were further made to study the antioxidant properties of C. tamala leaves.&#x0D; Materials and Methods: The diabetic rats were administered orally with the aqueous leaves extracts of Cinnamonum tamala (250 mg/kg) for 30 days. The results were compared with standard drug Tolbutamide.&#x0D; Result: The alloxan treated diabetic control rats showed a significant increase in the plasma glucose, glycosylated hemoglobin (HbA1C), glucose-6-phosphatase, aldolase, LDH, ALT, AST, ALP and GGT activity, freeradicals formation with a concomitant decrease in glycogen content in the liver and serum insulin level and phosphoglucoisomerase and hexokinase activity in tissues as compared to normal control rats. Oral administration of C. tamala extract for 30 days showed significant result as compared to Tolbutamide and diabetic control rats.&#x0D; Conclusion: On the basis of above findings it can be concluded that extracts of C. tamala to alloxan induced diabetic rats showed significant positive changes in the biochemical and histopathological parametersrelated to carbohydrate and protein metabolism.

Plasma antioxidant and hepatic enzymes activity, thyroid hormones alterations and health status of liver tissue in common carp (Cyprinus carpio) exposed to lufenuron

The aim of this study was to determine the effect of lufenuron as new practical pesticide on the health of one important fish species in aquaculture, common carp. The LC50 of lufenuron after 96 h was 1.089 mg/L in juvenile common carp (48 ± 4.25 g in weight). Behavior and mortality were investigated during the acute toxicity. The fish showed loss of equilibrium, erratic and lateral swimming and motionless. To determine the chronic effects of lufenuron, the fish distributed into 8 tanks as two treatments (4 tanks per treatment). They were exposed to 0 (control) and lufenuron (0.1 mg/L; 10% LC50-96 h concentration) and sampled at 7th and 21st days for blood biochemical analyses and at 21st day foe liver histopathological examinations. Plasma total protein and globulin levels of the lufenuron-exposed fish decreased significantly compared to the control fish. Lufenuron exposure increased plasma ALP, ALT and AST activities compared to the control group. Sampling time and lufenuron exposure had interaction effect on the plasma LDH activity. The plasma LDH activity of the lufenuron-exposed fish increased after 7 days exposure compared to the control group, but showed no significant difference compared to the control group after 21 days. The plasma T3 level declined in the lufenuron-exposed fish without significant changes in the plasma T4 levels. The plasma SOD activity in the lufenuron-exposed fish increased compared to the control group at the first sampling time, but there was no significant difference in the plasma SOD activities of the lufenuron-exposed and control fish after 21 days. Lufenuron exposure and sampling time had no independent or interaction effects of the plasma CAT activities. Plasma TBARS levels of the lufenuron-exposed fish had no significant difference compared to the control group after 7 day, but significantly increased after 21 days lufenuron exposure. Hepatocyte necrosis, melanomacrophage aggregates and sinusoidal space expansion were observed in the liver samples of the lufenuron-exposed fish.

The IRE1 signaling pathway is involved in the protective effect of low-dose LPS on myocardial ischemia-reperfusion injury

AimThe IRE1 signaling pathway is implicated in I/R injury. However, little is known about the involvement of this pathway in low-dose LPS treatment of myocardial I/R injury. Thus, an attempt was made to determine the relationship between the IRE1 pathway and I/R injury using rats or in vitro H9C2 cell myocardial I/R injury models. Main methodsSprague-Dawley rats and cultured H9C2 cells were pretreated with low-dose LPS and subjected to myocardial I/R injury models. Key findingsLow-dose LPS did not affect normal rat or cellular function. Compared with the I/R group, treatment with LPS attenuated myocardial apoptosis, decreased plasma LDH and CK-MB activities, reduced myocardium infarct size, and downregulated caspase-3 expression. Moreover, the protein or mRNA expression levels of the IRE1 signaling pathway-related proteins Grp78, IRE1, p-ASK1, ASK1, p-JNK, and JNK were notably increased during I/R injury but significantly decreased by low-dose LPS treatment both in rats and in H9C2 cells. SignificanceLow-dose LPS exhibited therapeutic effects in myocardial I/R injury. Most importantly, the cardioprotective mechanism of low-dose LPS may be associated with the IRE1 signaling pathway.

The protective effect of curcumin against aluminum chloride-induced oxidative stress and hepatotoxicity in rats

Aluminum is recognized as a public health concern because of its potential toxic effects on human health. Therefore, the present experiment was undertaken to determine the effectiveness of curcumin (CUR) in reducing the hepatotoxicity induced by aluminum chloride (AlCl3) in animals. In this experimental study, forty male rats were allocated to five groups (N = 8), viz. no treatment (control), solvent (DMSO or distilled water), CUR (10 mg/kg B.W.), AlCl3 (10 mg/kg B.W.), and CUR+AlCl3 (each with 10 mg/kg B.W.). Treatments were performed by intra-peritoneal injections for 28 days. On the final day, animals were sacrificed, and liver function markers in blood plasma, hepatic antioxidants, and lipid peroxidation index in liver homogenate were estimated. AlCl3 treatment resulted in a significant increase in plasma AST, ALT, ALP and LDH activities with decreased total protein compared to control. AlCl3 significantly reduced superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels but increased malondialdehyde (MDA) level in the liver compared to control. AlCl3 also caused various histopathological changes in the livers of rats. Curcumin could normalize nearly all these parameters. CUR improved levels of changes in different parameters when was combined with AlCl3. It is concluded that CUR has beneficial effects being able to antagonize AlCl3 toxicity.

Potential antioxidant properties and hepatoprotective effects of Juniperus phoenicea berries against CCl4 induced hepatic damage in rats.

To investigate the antioxidant and hepatoprotective properties of Juniperus phoenicea (J.phoenicea) berries against CCl4-induced oxidative damage in rats. Hepatotoxicity was induced in albino Wistar rats by single dose of CCl4 dissolved in olive oil (1mL/kg BW, 1/1 in olive oil, i.p.). Aqueous extract of J.phoenicea berries (AEJP) was administered at the dose of 250mg/kg/day by gavage for 12 days. Obtained results revealed that administration of CCl4 caused a significant increase in plasma ASAT, ALAT, ALP and LDH activities and total bilirubin concentration, compared to the control group. While, albumin and total protein concentration were significantly lower. Additionally, a significant decrease in the level of hepatic GSH, GPx and GST activities associated with a significant increase of MDA content in CCl4 group than those of the control. However, the treatment of experimental rats with AEJP prevented these alterations and maintained the antioxidant status. The histopathological observations supported the biochemical evidences of hepatoprotection. The results of the present investigation indicate that J.Phoenicea possesses hepatoprotective activity and this effect was may be due to its antioxidant properties.

5-Hydroxydecanoate Abolishes Cardioprotective Effects of a Structural Analogue of Apelin-12 in Ischemia/Reperfusion Injury

Chemically modified peptide apelin-12 (MA) with enhanced resistance to degradation by proteolytic enzymes is able to protect the heart against myocardial ischemia and reperfusion. This study was aimed to explore the role of mitochondrial ATP-sensitive K+-channels (mitoKATP) in effects of MA on myocardial energy state and membrane integrity in ischemia/reperfusion (I/R) injury. Isolated perfused working rat hearts were used to simulate global ischemia and reperfusion. Acute myocardial infarction was induced by coronary artery occlusion followed by restoration of coronary blood flow in anesthetized rats. Myocardial infarct size and cardiac dysfunction were used as indices of I/R injury at the end of reperfusion. Co-infusion of 5-hydroxydecanoate (5HD), the mitoKATP blocker, along with MA before ischemia significantly decreased functional recovery of isolated hearts as compared to administration of MA alone. These effects were accompanied by increased LDH release in the myocardial effluent, reduced restoration of myocardial ATP, AN, Cr, adenylate energy charge (AEC), and lactate accumulation. Coadministration of 5HD and MA at the onset of reperfusion substantially reduced infarct-limiting effect of the peptide in rats in vivo and increased the plasma LDH and CK-MB activity compared with MA treatment. Additionally, 5HD abolished MA influence on the metabolic state of the area at risk (AAR) at the end of reperfusion. In this case, the contents of metabolites and AEC in the AAR did not differ significantly from the values in control. Therefore, restoration of myocardial energy metabolism and sarcolemma integrity via activation of mitoKATP may be of critical importance for MA-induced protection against I/R injury.

Effects of dietary extra virgin olive oil and its fractions on antioxidant status and DNA damage in the heart of rats co-exposed to aluminum and acrylamide.

Oxidative stress generated by an excessive production of free radicals has been linked to the development of several health problems such as cardiovascular diseases. We investigated the protective efficacy of Extra Virgin Olive Oil (EVOO) and its lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) against the cardiotoxicity and DNA damage induced by co-exposure to aluminum (AlCl3) and acrylamide (ACR). Rats were divided into eight groups of six each: controls, AlCl3 (50 mg per kg body weight) administered via drinking water and ACR (20 mg per kg body weight) given by gavage, combined group plus EVOO (300 μl); combined group plus the hydrophilic fraction (1 ml); combined group plus the lipophilic fraction (300 μl); extra virgin olive oil (EVOO) and its fractions were administered daily by gavage for 21 days. Three other groups, considered as positive controls, received either EVOO, OOLF or OOLH. Exposure of rats to both AlCl3 and ACR provoked oxidative stress objectified by an increase in MDA, AOPP and a decrease in GSH, NPSH and vitamin C levels. The activities of CAT, GPx and SOD were also decreased. EVOO and its OOLF fraction exhibited a pronounced enhancement of antioxidant status while a partial recovery in the antioxidant status was obtained with the OOHF fraction. Plasma LDH and CK activities, TC, LDL-C levels, TC/HDL-C and LDL-C/HDL-C ratios were increased, while HDL-C and TG decreased in rats treated with both AlCl3 and ACR. Co-administration of EVOO, OOLF or OOHF to treated rats restored cardiac biomarkers and lipid profile to near-normal values. Histological studies and DNA damage confirmed the biochemical parameters and the beneficial role of EVOO and its two fractions. Our results suggest that extra virgin olive oil and its two fractions can decrease the frequency of cardiac complications and genotoxicity.

Acute exposure to a common suspended sediment affects the swimming performance and physiology of juvenile salmonids

To study the effects of an acute exposure to turbidity generated by suspended sediment, we examined swimming performance (Ucrit) and related metabolic parameters in individual and groups of juvenile trout at three different concentrations of calcium carbonate. To investigate differences among strains or provenience, we compared one strain of rainbow trout (Oncorhynchus mykiss; RBT) and one strain of brown trout (Salmo trutta; BNT) from a common hatchery and one RBT strain from a separate hatchery. In general, trout swum individually or in groups exhibited a decrease in Ucrit as turbidity increased. Both RBT strains were more similar to each other and were impaired to a larger extent in swimming performance than BNT, which was less impacted. For groups, indicators of aerobic metabolism were elevated while those of anaerobic metabolism were depressed. Specifically, citrate synthase activities and glucose levels tended to be greater while plasma lactate and LDH activities were reduced. Lactate and LDH levels in individually swum trout under sediment exposure suggest a greater similarity of fish from the same provenience. We suggest that acute exposures to environmentally relevant turbidities generated by fine suspended sediment may cause a reduced Ucrit, and that these changes may be related to changes in the utilization of aerobic and anaerobic pathways.

Heavy metal pollution monitoring in the northern coast of Hormuz Strait (Persian Gulf): plasma enzyme variations in Periophthalmus waltoni

Coastal waters in the northern part of Hormuz Strait (Persian Gulf) receive large inputs of anthropogenic pollutants. This study was made to determine the effects of heavy metals concentration on plasma enzymes of Periophthalmus waltoni by monitoring marine pollution in this area. Based on this, there was a positive correlation between heavy metal concentrations in sediment and tissue samples, of which Zn and Pb had significant positive correlations (P < 0.05). The plasma enzyme levels were higher in fish from the polluted location, whereas no significant differences were found for alkaline phosphatase and alanine aminotransferase (P < 0.01), suggesting a change in protein metabolism, rather than a consequence of cell permeability and integrity alterations and could be an adaptive response to metal exposure. On the contrary, plasma enzyme content in the blood showed a tendency positive with heavy metals concentrations in fish samples (P < 0.01). The higher heavy metals tissue content may affect the liver, causing some degree of structural damage. The results of this study indicate that plasma aspartate aminotransferase and LDH activity could be used as a metal contamination biomarker in estuaries.

Melatonin protects against ischemic heart failure in rats

Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10mg/kg) for 4weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β-D-glucuronidase, β-galactosidase, β-D-N-acetyl-glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase-3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin-3 levels were also determined by histological analyses. In the vehicle-treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure.

The PI3K/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia/reperfusion injury in rats

To explore the mechanisms underlying the protection by SO2 preconditioning against rat myocardial ischemia/reperfusion (I/R) injury. Male Wistar rats underwent 30-min left coronary artery ligation followed by 120-min reperfusion. An SO2 donor (1 μmol/kg) was intravenously injected 10 min before the ischemia, while LY294002 (0.3 mg/kg) was intravenously injected 30 min before the ischemia. Plasma activities of LDH and CK were measured with an automatic enzyme analyzer. Myocardial infarct size was detected using Evans-TTC method. The activities of caspase-3 and -9 in myocardium were assayed using a commercial kit, and the levels of p-Akt, Akt, PI3K and p-PI3K were examined with Western blotting. Pretreatment with SO2 significantly reduced the myocardial infarct size and plasma LDH and CK activities, as well as myocardial caspase-3 and -9 activities in the rats. Furthermore, the pretreatment significantly increased the expression levels of myocardial p-Akt and p-PI3K p85. Administration of the PI3K inhibitor LY294002 blocked all the effects induced by SO2 pretreatment. The results suggest that the PI3K/Akt pathway mediates the protective effects of SO2 preconditioning against myocardial I/R injury in rats.

Comparative Assessment of Melatonin-Afforded Protection in Liver, Kidney and Heart of Male Mice against Doxorubicin Induced Toxicity

Melatonin (MEL) was investigated for protection against the anthracycline antibiotic doxorubicin (Dox) that is well known for its oxidative damage to various body organs. It was aimed to have a comparison of this protection to heart, liver and kidney in the treated subjects. In this study, groups of mice were treated with Dox and melatonin and their individual or combined effects were evaluated by assessing lipidperoxidation, non-protein sulfhydryls (NP-SH) and nitrate/nitrite (NO) contents in these tissues. Plasma aminotransferases, LDH and CK-MB enzyme activities were measured. Moreover, these tissues were subject to histopathological assessment. MEL co-treatment significantly prevented any rise in lipidperoxides more significantly in heart and liver as compared to kidney. In tandem, MEL prevented a decline in GSH that was observed by Dox alone in liver and kidney. Dox significantly increased total NO levels in all the tissues. Melatonin at both dose levels could not afford protection against nitrosative stress. MEL in combination treatment provided significant (P

Determination of Oxidative Energy Metabolism and Plasma LDH Isoenzyme Patterns of Dolphins

In this study, oxidative energy metabolism was determined in 5 captive bottlenose dolphins (Tursiops truncatus), and subsequently compared to 6 Thoroughbred riding horses, and 12 lactating Holstein cows in order to assess symmorphosis of each animal species. Plasma metabolites profile, plasma MDH (M) and LDH (L) activities, M/L ratio, and plasma LDH isoenzyme distribution patterns were all examined. Overall, dolphins appear to have the greatest level of oxidative energy metabolism amongst horses and cows, due to having the greatest levels of plasma MDH activity. In addition, dolphin energy production/usage efficiency, via oxidative metabolism, was considered to be second (M/L ratio = 0.49) behind that of horses (M/L ratio = 0.79), possibly due to an increased reliance of non-oxidative energy metabolism over horses. In spite of demonstrating the lowest oxidative energy production/usage efficiency (M/L ratio = 0.15), cows also demonstrated the highest plasma LDH activity amongst all animal species. Although all animal groups displayed differing plasma LDH isoenzyme distribution patterns, dolphins and horses demonstrated a similarity with LDH-3 isoenzyme predominating in plasma; whereas LDH-1 isoenzyme predominates in cow plasma, thus inferring differences in oxidative/non-oxidative metabolism for energy generation/usage. Therefore, plasma MDH and LDH activity levels, M/L ratio, and plasma LDH isoenzyme pattern can all be useful indicators for better understanding oxidative energy metabolism and monitoring of captive animals' health. As it is not easy to obtain tissue samples from animals, the development of blood indicators for evaluating whole body metabolic state is necessary.