MDA Activity Research Articles

Toxicity and Disruptive Impacts of Fenhexamid Fungicide Against the Green Alga, Chlorella vulgaris.

Fenhexamid is one of the most extensively used fungicides against several plant pathogens. The green alga Chlorella vulgaris can be used as a model organism for toxicological tests in aquatic environments. The toxicity of fenhexamid was evaluated and the sub-lethal concentrations (LC10, LC25, and LC50) were determined after 24, 48, and 96h of exposure. The physiological responses of C. vulgaris to fenhexamid exposure including growth, photosynthetic efficiency, as well as antioxidant activities were used to investigate its impacts on aquatic organisms. The results showed a high reduction in cell number of C. vulgaris in a concentration-dependent manner, with maximum reduction up to 62.9% after 96h exposure to 120 µg. L−1 fenhexamid. Also, a remarkable decrease in the concentration of chlorophyll a, b and total chlorophyll with 2.04, 1.06, and 2.3-fold time, respectively. The content of antioxidant enzymes elevated after exposure to fenhexamid, indicating the oxidative damage in the algal cell after treatment. The activity of GSH, MDA, and SOD enzymes elevated by 41.3%, 82.8%, 65.3% respectively, after 96h exposure to 120 µg. L−1 fenhexamid, While the content of POD and CAT enzymes increased by 56.1% and 58%, respectively after 24h of exposure. Examination by electron microscopy shows high damage in the cytomembrane and the cell wall in addition to increasing in size and number of the starch granules which indicate high stress associated with exposure to the tested fungicide. Therefore, preventing or at least reducing the broad use of fenhexamid as a fungicide becomes an urgent necessity to protect aquatic organisms.

Evaluation of Blood Oxidant/Antioxidant Changes and Testicular Toxicity after Subacute Exposure to Cadmium in Albino Rats: Therapeutic Effect of Nigella sativa Seed Extracts.

Cells and tissues of the body are prone to oxidative damage as a result of an increased level of reactive oxygen species and nitrogen radical beyond the detoxifying ability of the endogenous antioxidant system. This study aimed to evaluate the ameliorative effect of methanolic extracts of Nigella sativa (MENS) against cadmium-induced blood oxidative stress and testicular toxicity in albino rats. Twenty-five (25) male albino rats, weighing (200 ± 20g), were randomly grouped into five groups (A-E). Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5 mg/kg) only, group C received CdCl2 and low dose MENS (300 mg/kg, oral), group D received CdCl2 and high dose MENS (600 mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200 mg/kg, oral), for 14 days. No treatment was administered to group A (Normal control). The oxidative state of the blood was assessed by measuring the blood levels or activities of MDA, CAT, GSH and SOD; while testicular injury was assessed by measuring serum testosterone level using ELISA. The testes were harvested for histopathological examination. The results showed that cadmium induced a marked elevation in the level of MDA, and a decrease in SOD, CAT and GSH levels or activities (p<0.05 or p<0.01); but no significant alteration in the serum testosterone level was found (p>0.05); Histopathological studies on the testes showed that cadmium significantly induced testicular injury, which was however ameliorated by the seed extract of N. sativa. We conclude that N. sativa seed extract is potentially testiculoprotective and attenuates oxidative stress against harmful chemical toxins such as cadmium.

Chilling and Heat Stress-Induced Physiological Changes and MicroRNA-Related Mechanism in Sweetpotato (Ipomoea batatas L.).

Sweetpotato (Ipomoea batatas (L.) Lam.) is an important industrial and food crop. Both chilling and heat stress inhibits sweetpotato growth and development and then affects yield. However, the physiological and molecular mechanisms of sweetpotato response to chilling and heat stress is unclear. In this study, we investigated the effect of extreme temperature on sweetpotato physiological response, with a focus on oxidative stress and the potential microRNA (miRNA)-mediated molecular mechanism. Our results showed that both chilling and heat stress resulted in accumulation of reactive oxygen species (ROS), including H2O2 and O2–, and caused oxidative stress in sweetpotato. This further affected the activities of oxidative stress-related enzymes and products, including SOD, POD, and MDA. Both chilling and heat stress inhibited POD activities but induced the enzyme activities of SOD and MDA. This suggests that sweetpotato cells initiated its own defense mechanism to handle extreme temperature-caused oxidative damage. Oxidative damage and repair are one mechanism that sweetpotato plants respond to extreme temperatures. Another potential mechanism is miRNA-mediated gene response. Chilling and heat stress altered the expression of stress-responsive miRNAs in sweetpotato seedlings. These miRNAs regulate sweetpotato response to extreme stress through targeting individual protein-coding genes.

α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1β were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1β. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.

In vivo assessment of the probiotic potentials of three host-associated Bacillus species on growth performance, health status and disease resistance of Oreochromis niloticus against Streptococcus agalactiae

Four weeks feeding trial was conducted to assess the in vivo probiotic potentials of three host-associated Bacillus species in O. niloticus. The fish were divided into five treatment groups and fed with diets containing no bacteria (group CT), B. velezensis TPS3N (group V), B. subtilis TPS4 (group S), B. amyloliquefaciens TPS17 (group A) and a 5th group which comprised the combination of the three Bacillus species at a ratio 1:1:1 (group CB). At the end of the feeding trial, enhanced growth performance in terms of final weight (FW), weight gain (WG), specific growth rate (SGR) as well as significantly lower (P < .05) feed conversion ratio (FCR) were recorded in the Bacillus treatment groups with the CB group having the best performance. Improved immune and biochemical (P < .05) (nitric oxide (NO), immunoglobulin M (IgM), lysozyme (LZM), acid phosphatase (ACP), and alkaline phosphatase (AKP)) indexes, antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) and digestive enzymes (lipase and trypsin) were also recorded in the treatment groups relative to the CT group. Significantly lower (P < .05) GOT and MDA activities were also observed in the V, S, A, and CB groups than the CT groups. Growth-related genes GHR-1 and IGF-1 were upregulated significantly (P < .05) in both liver and head kidney (HK) of fish fed Bacillus supplemented diets. Likewise, the CB group induced significant upregulation (P < .05) of TNF-α, TLR-2, IgM (except in the liver) and C-LYZ in both liver and HK. A subsequent challenge test with S. agalactiae resulted in cumulative mortalities (%) of 60%, 33%, 27%, 20%, and 13% in the CT, V, S, A, and CB treatment groups respectively. It was therefore concluded from this experiment that dietary inclusion of the Bacillus species singularly or in combination could elicit probiotic effects and protect O. niloticus against S. agalactiae infection.

Seasonal variations of heavy metals in the marine bivalve Cerastoderma glaucum (Bruguière, 1789) from Temsah Lake, Ismailia, Egypt, and their relation to anti‌oxidant enzymes

Cerastoderma glaucum is a common bivalve in Temsah Lake. It plays important direct and/or indirect roles in the nutrient cycle. This work determined the seasonal variation of heavy metals [copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), zinc (Zn), chromium (Cr), nickel (Ni), cobalt (Co), cadmium (Cd) and lead (Pb)] in the tissue of the investigated bivalve, and the effect of these metals on the antioxidant enzymes. The results revealed that the greatest values for all studied metals in the soft tissues of C. glaucum occurred during winter and autumn seasons, while the least values were recorded during spring and summer seasons. Mg and Fe concentrations were significantly higher in all seasons when compared with all other metals. The concentrations of metals, such as Mn, Ni, Fe, and Cr were present beyond the WHO recommended standards, especially during winter and autumn seasons. Also, this study showed highly significant increase in lipid peroxidation (MDA) activity during autumn and winter seasons that was associated with a decrease in the mean activity levels of catalase (CAT) and glutathione peroxidase (GPx) than summer season and decrease in superoxide dismutase (SOD) activity than spring season. These results related to high heavy metals concentrations, such as Cu, Fe, and Zn during the autumn season, and Mg, Mn, Cr, Co, and Ni during the winter season. Moreover, the present study recorded positive significant correlations between MDA activity and Cu, Cr and Fe concentrations, and significantly negative correlations between MDA activity and SOD activity, between CAT activity and Ni and Mn, and between GPx and Mn, Cr and Fe. So, the present study suggests that MDA and antioxidant enzymes (CAT, GPx and SOD) can be used as biomarkers to reflect the level of heavy metal pollution stress, especially Fe and Cr in the soft tissues of C. glaucum.

Physiological and Molecular Effects of Silver Nanoparticles Exposure on Purslane (Portulaca oleracea L.)

Due to the antifungal and antibacterial properties, silver nanoparticles (AgNPs) are now widely used in consumer products. In this research, the effects of various concentrations of AgNPs (0, 2.5, 5, 10, 20, 40 and 80 ppm) on growth, contents of micro- and macroelements, physiological traits and expression of PAL and GSH genes of purslane (Portulaca oleracea L.) plants were investigated. The results showed that application of AgNPs resulted in a dose-dependent enhancement in accumulation of silver (Ag) in both root and leaf tissues, however, the Ag accumulated at the root more than the leaf at all levels of the AgNPs treatment. AgNPs treatment over 20 ppm reduced the growth, biomass production and accumulation of macroelements (Ca and Mg) and microelements (Zn, Cu, Mn and B) and increased contents of H2O2, MDA and DPPH scavenging activity. Application of AgNPs also increased the activity of antioxidant enzymes such as SOD, CAT and POD enzymes compared to control treatments. The activity and expression of PAL and CHS enzymes significantly increased under treatment of AgNPs. Our results indicate that increasing the activity of antioxidant enzymes and regulating the expression and activity of PAL and CHS enzymes are mechanisms to counteract the oxidative stress induced by AgNPs in the purslane plants.

Isolation and functional validation of stress tolerant EaMYB18 gene and its comparative physio-biochemical analysis with transgenic tobacco plants overexpressing SoMYB18 and SsMYB18.

MYB transcription factors are one of the most important mediators for the survival of plants under multiple stress responses. In the present study, EaMYB18, encoding a single R3 repeat MYB DNA binding domain was isolated from stress-tolerant wild relative species of sugarcane Erianthus arundinaceus. In silico analysis of 948bp coding mRNA sequence of EaMYB18 exhibited the presence of four exons and three introns. Further, the EaMYB18 gene was transformed in tobacco and its stable inheritance was confirmed through antibiotic resistance screening, PCR amplification and Southern hybridization blotting. Results of the estimation of MDA, proline, total chlorophyll and antioxidant activities of EaMYB18 transgenic tobacco lines exhibited least oxidative damage under drought and cold stress over the untransformed ones, the over-expression of EaMYB18 has improved drought and cold stress tolerance ability in tobacco. The comparative physiological and biochemical analysis of transgenic tobacco plants overexpressing SoMYB18, SsMYB18 and EaMYB18, revealed that the EaMYB18 and SsMYB18 transgenic plants demonstrated effective tolerance to drought and cold stresses, while SoMYB18 showed improved tolerance to salt stress alone. Amongst these three genes, EaMYB18 displayed the highest potential for drought and cold stress tolerances as compared to SoMYB18 and SsMYB18 genes.

The Beneficial Effects of Actinomycetales Immune Modulators in the Pancreas of Diabetic Rats.

Purpose: Type 1 diabetes mellitus (T1DM) has dramatically increased in recent years, especially in young people, and limits the life quality of the patients involved. Thus, many researchers are performing extensive studies to find alternative treatments for DM.Methods: Here, we evaluated the improvement effects of the heat-killed Actinomycetales species, including Gordonia bronchialis, and Tsukamurella inchonensis in streptozotocin (STZ)- diabetic rats by biochemical, immunological, and histopathological examinations.Results: The present findings exhibited a dramatic and progressive alteration in the serum levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) in the diabetic group, which were related to the blood glucose and insulin levels, oxidative stress defense (evaluated by TAC and MDA activities), and the pancreas biochemical indicators (such as amylase and lipase). More importantly, the present results were consistent with the histopathological findings, which included cellular degeneration, vascular congestion, hemorrhage, focal necrosis associated with mononuclear cell infiltration. Interestingly, all of the diabetic changes in the blood serum and tissues improved remarkably in the treated groups by Actinomycetales species.Conclusion: Surprisingly, most of the current diabetic complications effectively attenuated after oral administration of both Actinomycetales species, particularly with a high dose of T. inchonensis. Thus, it is concluded that the heat-killed Actinomycetales species can prevent and improve the progression of T1DM and its various complications profoundly.

Nifuroxazide attenuates experimentally-induced hepatic encephalopathy and the associated hyperammonemia and cJNK/caspase-8/TRAIL activation in rats

Hyperammonemia is a serious metabolic disorder associating with hepatic encephalopathy (HE) which occurs secondary to several forms of liver injury ranging from simple acute liver failure (ALF) to its most serious form; cirrhosis. The resent study highlights the possible ameliorative effect of oral nifuroxazide (25 mg/kg) against experimentally induced ALF and the subsequent HE in a well-standardized rat model. ALF and HE were induced in a rat model by I.P. injection of thioacetamide (TAA) (200 mg/kg) for 1 week at alternative days. Nifuroxazide administration for 14 days prior to and for further 7 days alongside TAA injection successfully attenuated TAA-induced ALF and HE; as demonstrated by the significant retraction in both brain and serum hyperammonemia with significant improvement in liver function biomarkers; ALT, AST, ALP, GGT, albumin, and serum total protein. This was associated with a significant restoration of both hepatic and brain oxidative stress incidences; MDA, SOD and catalase activities and GSH concentration. The observed improvement was associated with a significant reduction in liver and brain contents of c-Jun N-terminal kinase (cJNK); as an anti-inflammatory biomarker and a modulator of various pro- and anti-apoptotic proteins, caspase-8, and tumor necrosis factor-related apoptosis ligand (TRAIL); as biomarkers of apoptosis. In conclusion; the modulatory effect of nifuroxazide on cJNK/caspase-8/TRAIL signaling appears to underly its hepatoprotective effect and its ameliorative effect on HE progression.

Buddleja saligna Willd (Loganiaceae) Inhibits Angiotensin‐Converting Enzyme Activity in Oxidative Cardiopathy with Concomitant Modulation of Nucleotide Hydrolyzing Enzymatic Activities and Dysregulated Lipid Metabolic Pathways

Buddleja saligna Willd (Loganiaceae), mostly indigenous to South Africa is traditionally used in the treatment cardio‐dysfunctional related ailments amongst other diseases. The cardio‐protective effect of B. saligna was investigated in ferric‐induced oxidative cardiopathy. Hearts harvested from healthy male SD rats were incubated with 0.1 mM FeSO4 to induce oxidative damage and co‐incubated with B. saligna extract. Reaction mixtures without the extract served as negative control, while tissues without the extract or standard antioxidant (gallic acid) and pro‐oxidant served as the normal control. The tissues were analyzed for levels of glutathione, malondialdehyde, and nitric oxide as well as cholinergic, angiotensin‐converting enzyme (ACE), lipase, and purinergic enzymes activities, lipid profiles, fatty acid metabolic pathways and metabolites. Induction of oxidative damage significantly (p&lt;0.05) depleted the levels of GSH, SOD, catalase, and ENTPDase activities, while concomitantly elevating the levels of MDA, NO, ACE, acetylcholinesterase, lipase and ATPase activities. These levels and activities were significantly reversed on treatment with B. saligna. Treatment with B. saligna also led to depletion of cardiac cholesterol and LDL‐c levels, while elevating triglyceride and HDL‐c level. It also depleted oxidative‐induced lipid metabolites with concomitant generation of thirteen other metabolites. B. saligna also inactivated oxidative‐induced pathways for beta oxidation of very long chain fatty acids, glycerolipid metabolism, and fatty acid elongation in mitochondria. These results suggest that B. saligna protects against ferric‐induced oxidative cardiopathy by mitigating oxidative stress, while concomitantly inhibiting ACE, acetylcholinesterase and lipase activities, and modulating lipid spectrum and dysregulated metabolic pathways.Support or Funding InformationThis work was supported by research funding from the National Research Foundation; and the Department of Science and Innovation (DSI) through the IKS‐Based Technology Innovations, Pretoria, South Africa

STRAP reduces endoplasmic reticulum stress and apoptosis in cardiomyocytes and attenuates myocardial ischemia-reperfusion injury by activating PI3K/PDK1/Akt signaling pathway.

Myocardial ischemia-reperfusion injury (MIRI) is a common problem in heart-related diseases. The aim of this study was to explore the protective effects of STRAP on cardiomyocytes in the MIRI process and its mechanisms. We used SD rats to construct a MIRI model and increased the expression of STRAP in myocardial tissue by Entranster to detect the effect of STRAP on rat myocardial tissue. In addition, we cultured rat cardiomyocyte cell line H9c2 cells and constructed a hypoxia-reoxygenation model to detect the protective effect of STRAP on H9c2 cells. LY294002, an inhibitor of the PI3K/PDK1/Akt signaling pathway, was used to validate the mechanism by which STRAP protects cardiomyocytes. Overexpression of STRAP significantly reduced the activity of MDA in myocardial tissue and increased the activity of SOD. STRAP also substantially lowered CK and LDH levels in rat serum and increased Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity. In addition, overexpression of STRAP considerably reduced endoplasmic reticulum stress (ERS) and apoptosis levels in H9c2 cells. However, LY294002 attenuated the protective effect of STRAP on cardiomyocytes. STRAP reduces ERS and apoptosis in cardiomyocytes by activating the PI3K/PDK1/Akt signaling pathway, thereby reducing myocardial MIRI.

Behaviour and biochemical responses of the marine clam Ruditapes decussatus exposed to phosphogypsum

ABSTRACT The phosphate fertilizer and phosphoric acid industries increase phosphogypsum levels in the aquatic environment leading to various disturbing effects. In the present work, we investigated the bio-uptake of heavy metals following the exposure of Ruditapes decussatus to three concentrations of phosphogypsum, 10, 20 and 40 g kg−1, under laboratory conditions. The amounts of Zn, Cd and Pb in several organs of the clam Ruditapes decussatus was determined using inductively coupled plasma optical emission spectroscopy (ICP-OES). Phosphogypsum acts on the behaviour of R. decussatus by increasing filtration rates. The most treatments showed significantly higher metal concentration in all tissues than the controls. Excavation behaviour was altered in treated bivalves compared to controls. The filtration rate (FR) of clams was significantly affected by exposure to phosphogypsum. Indeed, FR increased in clams exposed to phosphogypsum. Phosphogypsum has decreased SOD, CAT and MDA activities in the gills, digestive gland, gonad and muscles according to the concentration indicating a defense against oxidative stress. AChE was significantly inhibited in clams from all the sampling sites compared to controls. The considered parameters could be useful biomarkers for the evaluation of phosphogypsum toxicity in threatened biota. This study was conducted as part of a further investigation into the use of a comprehensive approach combining chemical and biological parameters to assess the health status of the Gabes gulf population. It provides the first database referring to phosphogypsum contamination and its biological effect in this ecosystem. The present study fills in a needed gap in the literature.

Evaluation of the modulatory effects of Piper guineense leaves and seeds on egg albumin-induced inflammation in experimental rat models

Ethnopharmacological relevanceInflammation processes are implicated in many degenerative diseases. Piper guineense, a West African spice belonging to the Piperaceae family has been reported to contain anti-inflammatory agents. Aim of studyThis study determined the modulatory effects of methanolic extracts of Piper guineense leaves and seeds on egg albumin-induced inflammation in rats.Study design and methods: Inflammation in the hind paw was induced by injecting 0.1ml egg albumin subcutaneously. Treatments including diclofenac were given orally. Rectal temperature and paw size were monitored hourly for the first 3 h’ post-induction of inflammation and then at the 6th and 24th hour. Serum levels of CRP, MDA, LDH and GGT activities were determined at these hours. ResultsResults showed that egg albumin-induced inflammation caused a significant (p < 0.05) increase in paw size and rectal temperature. It further showed that treatment with the leaves and seed extracts reversed the effect of inflammation on serum levels of CRP and MDA, and on LDH and GGT activities similar to diclofenac in rats. ConclusionExtracts of the Piper guineense seed and leaves have potentials of being used as an anti-inflammatory agent but further studies need to be done to determine their toxicity and effects on immunological markers of inflammation.

Calcio-herbal formulation, Divya-Swasari-Ras, alleviates chronic inflammation and suppresses airway remodelling in mouse model of allergic asthma by modulating pro-inflammatory cytokine response

Asthma is a chronic allergic respiratory disease with limited therapeutic options. Here we validated the potential anti-inflammatory, anti-asthmatic and immunomodulatory therapeutic properties of calcio-herbal ayurvedic formulation, Divya-Swasari-Ras (DSR) in-vivo, using mouse model of ovalbumin (OVA) induced allergic asthma. HPLC analysis identified the presence of various bioactive indicating molecules and ICP-OES recognized the presence of Ca mineral in the DSR formulation. Here we show that DSR treatment significantly reduced cardinal features of allergic asthma including inflammatory cell accumulation, specifically lymphocytes and eosinophils in the Broncho-Alveolar Lavage (BAL) fluids, airway inflammation, airway remodelling, and pro-inflammatory molecules expression. Conversely, number of macrophages recoverable by BAL were increased upon DSR treatment. Histology analysis of mice lungs revealed that DSR attenuates inflammatory cell infiltration in lungs and thickening of bronchial epithelium. PAS staining confirmed the decrease in OVA-induced mucus secretion at the mucosal epithelium; and trichrome staining confirmed the decrease in peribronchial collagen deposition upon DSR treatment. DSR reduced the OVA-induced pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) levels in BALF and whole lung steady state mRNA levels (IL-4, -5, -33, IFN-γ, IL-6 and IL-1β). Biochemical assays for markers of oxidative stress and antioxidant defence mechanism confirmed that DSR increases the activity of SOD, Catalase, GPx, GSH, GSH/GSSG ratio and decreases the levels of MDA activity, GSSG, EPO and Nitrite levels in whole lungs. Collectively, present study suggests that, DSR effectively protects against allergic airway inflammation and possess potential therapeutic option for allergic asthma management.

Impairment of endothelial progenitor cells function in patient with mustard gas intoxication

Background: Sulfur mustard (SM), also known as mustard gas, was first widely used in the Iraq–Iran. After SM exposure, the most prominent clinical signs are the development of extensive non-healing skin wounds and pulmonary signs, persisting over long time. Since the most frequent complications in SM-intoxicated patients are respiratory and dermatologic lesions, and with respect to the important role of endothelial progenitor cells (EPCs) in the pathophysiology of these lesion, we conducted this study to recognize the potential effects of SM on biological features of EPCs in patients exposed with this gas.Methods: In this study, 30 patients with the history of SM exposure during the Iran–Iraq war (1984–1988), 27 patients with pulmonary signs with no history of SM exposure and 20 healthy participants were included. Cell population and function of EPCs were assessed 4 years post-exposure. For this purpose, circulating EPCs (cEPCs) were harvested and cultivated, then the biological features of these cells, including migratory, proliferative, and tubulogenic activities were analyzed. We also measured serum antioxidants levels and mRNA levels of some proangiogenic factors in EPCs from SM-intoxicated patients.Results: Our results showed lesser number of cEPCs in patients exposed with SM, which was associated with decreased proliferative, migratory, and tubulogenic activity of these cells. Also, we found the lesser serum activity of SOD, GPX and MDA in the SM group than in the healthy control group.Conclusions: SM exposure resulted in decreased proliferation and migration of EPCs, which was associated with decreased tubule formation and angiogenic factors.

The role of CGRP receptor antagonist (CGRP8-37) and Endomorphin-1 combination therapy on neuropathic pain alleviation and expression of Sigma-1 receptors and antioxidants in rats

BackgroundSpinal cord injury is one of the most common causes of neuropathic pain which is not responsive to common treatments. Owing to the adverse effects of drugs, it seems that the use of Calcitonin Gene-Related Protein (CGRP) receptor antagonist or Morphine and their combination could be an appropriate strategy for pain alleviation. MethodTo achieve the objective, fifty six male Wistar rats were divided into seven groups. CGRP8-37 and Endomorphin-1 alone, and in combinated administration, as bolus and continues dose. Both mechanical and cold allodynia, and mechanical hyperalgesia were evaluated before and also15 and 60 min after injection to indicate the efficacy of the therapies in the acute and chronic circumstances on pain induced by spinal cord compression injury. Sigma-1 receptor experssion, oxidant and antioxidant activity after the seven days of the drug adminestration were evaluated. ResultThe results showed that Endomorphin-1and CGRP8-37 injections were able to reduce neuropathic pain after spinal cord compression injury. Compared to Endomorphin-1, or CGRP8-37 monotherapy, combination therapy did not show more attenuating effects on the pain threshold. Compared to the continous administration of Endomorphin-1 alone, and CGRP8-37 alone, the continous combination therapy did not reduce the pain further. Molecular studies disclosed the increased expression of the Sigma1 receptor, in the spinal cord after administration of Endomorphin-1, and CGRP8-37 alone, as well as combination therapy. Although, an increase in GPx and SOD activity, and decrease in MDA activity was observed in the combination therapy. ConclusionOur results demonstrate that either Endomorphin-1 or CGRP receptor antagonist is able to decrease the neuropathic pain after SCI but combination therapy by a CGRP receptor antagonist and Endomorphin-1 did not make any further reduction in pain sensation.

Chlorpyrifos induces redox imbalance-dependent inflammation in common carp lymphocyte through dysfunction of T-cell receptor γ.

Chlorpyrifos is a poisonous pesticide that is highly toxic to fish and aquatic organisms. However, there are fewer reports about how chlorpyrifos influences the redox balance of immune cells. Herein, the head kidney tissue treated with chlorpyrifos to do transcriptome analysis and TCR γ was screened out. Subsequently, we established TCR γ knockdown and overexpression carp head kidney lymphocyte models, respectively, by using RNA interference and pcDNA3.1. Real-time PCR, fluorescent staining, oxidation and antioxidant kit were used to detect the related factors. We found that TCR γ knockdown significantly increased the mRNA expression of HSP70 and HSP90 and decreased the mRNA expression of SOD and CAT. Meanwhile, TCR γ knockdown reduced the activities of GSH, GSG-PX, T-AOC, CAT and SOD and increased the content of MDA and H2 O2 and activities of iNOS. Adverse results were obtained in TCR γ overexpression group. Additionally, TCR γ knockdown significantly increased the mRNA expression of IFN-γ, IL-1β, IL-8, IL-10, Nrf2 and NF-κB, but relieved TCR γ overexpression, in which the process of inflammation was activated. Our results reported here indicated that chlorpyrifos induces redox imbalance-dependent inflammation in common carp lymphocyte through dysfunction of T-cell receptor γ, and HSPs play potential protective role in entire process.

Anti-Inflammatory and Antioxidant Effects of Acetyl-L-Carnitine on Atherosclerotic Rats.

BackgroundThe purpose of the present study was to evaluate the regulatory effects of acetyl-L-carnitine (ALCAR) on atherosclerosis in Wister rats and to explore its anti-atherosclerotic mechanism.Material/MethodsWe randomly divided 32 Wister rats into 4 groups: a normal diet group (control group, n=8), a normal diet+ALCAR group (ALCAR group, n=8), an atherosclerosis group (AS group, n=8), and an atherosclerosis+ALCAR group (AS+ALCAR group, n=8). The serum lipid distribution, oxidative stress, inflammatory factors and adiponectin (APN) in the blood, and heart and aortic tissues were determined using the standard assay kits, xanthine oxidase method, and ELISA, respectively. HE staining was performed to observe aortic pathology structure change, and the level of angiotensin II (AngII) in the aorta was assessed using radioimmunoassay. In addition, real-time quantitative PCR and Western blot analysis were applied to detect the expression of iNOS, IL-1β, TNF-α, and CRP in the aortic and heart tissues.ResultsCompared with the AS group, the levels of serum TC, TG, LDL, and VLDL in rats decreased significantly, while HDL level significantly increased in the AS+ALCAR group. ALCAR administration enhanced the SOD and GSH-Px activities and decreased MDA activity. APN level was significantly elevated in the AS group, but ALCAR had no significant effect on APN. Further, ALCAR reduced the expressions of inflammation factors TNF-α, IL-1β, iNOS, and CRP, and the concentration of AngII in serum, aortic, and heart tissues.ConclusionsALCAR can inhibit the expressions of inflammatory factors and antioxidation to suppress the development of atherosclerosis by adjusting blood lipid in the myocardium of AS rats.

Knockdown of IL-32 protects PC12 cells against oxygen-glucose deprivation/reoxygenation-induced injury via activation of Nrf2/NF-κB pathway.

Cerebral ischemia/reperfusion injury (IRI) is one of major causes of ischemic organ damage. It is well established that inflammatory cytokines serve as regulatory factors in cerebral oxygen glucose deprivation/reoxygenation (OGD/R). However, the involving mechanism is not clear enough. OGD/R PC12 cells were used as a hypoxia/reoxygenation model. IL-32 expression and cell viability were detected by qRT-PCR and CCK-8 assay, respectively. Cell apoptosis were determined by flow cytometry and western blotting. Protein levels of inflammatory factors, and the activity of MPO, MDA and SOD were analyzed. Furthermore, western blot assay was carried out to assess protein levels of Nrf2, keap1, NQO-1, p-p65, p-IκBα, p65 and IκBα. The results revealed that IL-32 expression was significantly upregulated in PC12 cells induced by OGD/R. Nrf2, keap1 and NQO-1 level was reduced while phosphorylation level of p65 and IκBα was up-regulated in OGD/R-induced PC12 cells. Mechanism investigations found that IL-32 silence elevated the level of Nrf2, Keap1 and NQO-1, reduced p-p65 and p-IκBα level, and regulated the contents of TNF-a, IL-1β, IL-6 and MCP-1 in OGD/R PC12 cells. In addition, knockdown of IL-32 suppressed production of intracellular ROS, elevated SOD activity, reduced MPO and MDA content, and enhanced cell viability. Furthermore, cell apoptosis was induced in OGD/R PC12 cells with IL-32 silence. However, Nrf2 inhibitor reversed the effects of IL-32 knockdown on OGD/R PC12 cells. This research suggests that IL-32 silence may alleviate OGD/R and Nrf2 plays an important role in the protection by IL-32 silence on PC12 cells induced by OGD/R.