Peroxidation Enzymes Research Articles

Ablation of mitophagy receptor FUNDC1 accentuates septic cardiomyopathy through ACSL4-dependent regulation of ferroptosis and mitochondrial integrity

Sepsis evokes compromised myocardial function prompting heart failure albeit target therapy remains dismal. Our study examined the possible role of mitophagy receptor FUNDC1 in septic cardiomyopathy. A sepsis model was established using cecal ligation and puncture (CLP) in FUNDC1 knockout (FUNDC1−/−) and WT mice prior to the evaluation of cardiac morphology, echocardiographic and cardiomyocyte contractile, oxidative stress, apoptosis, necroptosis, and ferroptosis. RNAseq analysis depicted discrepant patterns in mitophagy, oxidative stress and ferroptosis between CLP-challenged and control murine hearts. Septic patients displayed cardiac injury alongside low plasma FUNDC1 and iron levels. CLP evoked interstitial fibrosis, cardiac dysfunction (lowered ejection fraction, fractional shortening, shortening/relengthening velocity, peak shortening and electrically-stimulated intracellular Ca2+ rise, alongside increased LV end systolic diameter and relengthening duration), O2− buildup, apoptosis, necroptosis, and ferroptosis (downregulated GPX4 and SLC7A11), the responses of which were accentuated by FUNDC1 ablation. In particular, levels of lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) were upregulated following CLP procedure, with a more pronounced response in FUNDC1−/− mice. Co-immunoprecipitation and interaction interface revealed an evident interaction between FUNDC1 and ACSL4. In vitro studies revealed that the endotoxin lipopolysaccharide provoked cardiomyocyte contractile and lipid peroxidation anomalies, the responses were reversed by the mitophagy inducer oleanolic acid, inhibition of ACSL4 and ferroptosis. These findings favor a role for FUNDC1-ACSL4-ferroptosis cascade in septic cardiomyopathy.

Aberrant hepatic glucose levels and cellular damage reversed by Cucurbita maxima blossoms on experimental models

ObjectivesInvestigate the ameliorating effects of Pumpkin flowers (Cucurbita maxima) 10% and 20% fortified cake on cellular damage caused by alloxan-induced diabetic rats. MethodsForty adult male albino rats of approximately weigh about 180 ± 5 g were obtained and divided into five distinct groups to determine the effect of C. maxima flowers enriched (CMFP) cake two different concentrations (10 % and 20 %) had any beneficial impacts on rats with a single dose of 40 mg/kg alloxan to induce diabetes. ResultsThe observations on the blood insulin, blood sugar, lipid profile, serum liver biomarkers, lipid peroxidation enzyme markers, and pro-oxidative mediators showed that oral administration of 10% and 20% CMFP cake lowers the blood sugar, Total Cholesterol (TC), Low-Density Lipoprotein (LDL), Very Low-Density lipoprotein (VLDL) and Triglyceride (TG). In rat treated with alloxan, the levels of alanine transaminase (ALT), alkaline phosphatase ALP), aspartate transaminase (AST) and the levels of malondialdehyde (MDA), thiobarbituric acid reactive compounds (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LOOH) were significantly reduced. Moreover, blood serum insulin, high density lipoprotein (HDL), Superoxide dismutase (SOD), Catalase (CAT) and reduced glutathione (GSH) increased simultaneously; These results verified that the 20% CMFP cake was the best treatment specially in decreasing hepatic lipid peroxidation with levels between 54%, 49.5% and 75.2 % for LOOH, CD and TBARS consequently. ConclusionSince, pumpkin blossoms contains a wide range of phytonutrients, pumpkin blossom has the potential to be a functional food source to incorporate into diabetics’ diets to manage the disease.

Anti-Platelet Activity of Sea Buckthorn Seeds and Its Relationship with Thermal Processing.

Sea buckthorn (Hippophae rhamnoides L.) is a tree or shrub with small, orange berries. Sea buckthorn seeds have shown many properties beneficial to human health, including antioxidant, anti-hypertensive, anti-hyperlipidemic, and retinoprotective activities. Seeds, as a component of food, are often exposed to high temperatures, which can increase or decrease their biological activity. In our previous study, we showed that both raw and roasted sea buckthorn seeds had significant antioxidant activity, which was measured in human plasma in vitro. In this paper, we evaluated the effect of extracts from raw and roasted sea buckthorn seeds on several parameters of hemostasis in vitro, including thrombus formation in full blood (measured by the Total Thrombus formation Analysis System-T-TAS), blood platelet activation (based on the exposition of P-selectin, the active form of GPIIb/IIIa on their surface and platelet-derived microparticles formation), aggregation (measured with impedance aggregometry), adhesion to fibrinogen and collagen, arachidonic acid metabolism in washed platelets stimulated by thrombin, and COX-1 activity. We also measured the levels of free 8-isoprostane in plasma and the total non-enzymatic antioxidant status of plasma. The extract from roasted seeds (50 µg/mL) significantly prolonged the time of occlusion measured by T-TAS-the AUC10 (area under the curve) value was decreased by approximately 18%. Both extracts decreased the exposition of the active form of GPIIb/IIIa on the surface of platelets activated with 10 μM ADP (by 38.4-62.2%) and 20 μM ADP (by 39.7-51.3%). Moreover, the extract from raw seeds decreased the exposition of P-selectin on the surface of platelets stimulated with 20 μM ADP (by 31.2-34.9%). The adhesion of thrombin-stimulated platelets to fibrinogen and collagen was inhibited only by the extract from roasted sea buckthorn seeds (by 20-30%). Moreover, the extract from raw seeds inhibited the level of TBARS (thiobarbituric acid-reactive substances, an indicator of enzymatic peroxidation of arachidonic acid) in washed platelets stimulated with thrombin; the activity of COX-1 was inhibited by both extracts, although the effect of the extract from raw seeds was stronger. These results indicate that sea buckthorn seeds have anti-platelet activity that is not decreased by thermal processing, but more research is needed to determine which exact chemical compounds and mechanisms are responsible for this phenomenon.

Neuroprotective effects of galectin‑1 on cerebral ischemia/reperfusion injury by regulating oxidative stress.

Oxidative stress contributes to the pathology of cerebral ischemia/reperfusion (I/R) injury. Galectin-1 has shown an anti-oxidative stress effect. The present study investigated whether this anti-oxidative stress effect can account for the neuroprotective actions of galectin-1 induced by cerebral I/R injury. A cerebral I/R injury model was created in C57Bl/6 mice by transient occlusion of the middle cerebral artery, after which the mice were treated with galectin-1 for 3 days. Infarct volumes were measured. A rotarod test and neurological deficit score assessment was performed to evaluate the neurological deficits. Oxidative stress was evaluated by measuring the levels of reactive oxygen species (ROS) and lipid peroxidation malondialdehyde (MDA), while the anti-oxidative stress status was assessed by measuring molecules such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidation enzyme (GSH-Px) in the ischemic cerebral hemisphere of mice. The inflammatory cytokines, including Interleukin 1 (IL-1), IL-6 and tumor necrosis factor alpha (TNF-α) were measured, and the expression of microglia was evaluated by immunohistochemistry in the ischemic cerebral hemisphere of mice. Galectin-1 treatment ameliorated neurological deficits and reduced infarct volumes in the mice model with cerebral I/R injury. Moreover, it was demonstrated that galectin-1 can significantly alleviate cerebral I/R injury in the ischemic cerebral hemisphere by decreasing the production of ROS and MDA, but increasing the production of CAT, SOD and GSH-Px. Galectin-1 treatment decreased microglia expression, and IL-1, IL-6 and TNF-α levels in the ischemic cerebral hemisphere of mice. Galectin-1 could improve the outcome of cerebral I/R injury by alleviating oxidative stress. Moreover, the neuroprotective effect of galectin-1 in cerebral ischemia could be related to its anti-oxidative stress effect.

Androgenic Anabolic Steroids Perturb Hepatocellular Tissue Damage Mediated by Oxidative Stress in the Presence of Endogenous Antioxidant

Objective of the study: Anabolic androgenic steroids (AASs) unlawfully misused for their anabolic effects has deleterious effects of major concerns in public health even in the presence of endogenously produced antioxidants. This study is to evaluate the interaction between AAS metabolites and endogenously produced superoxide dismutase (SOD) activity in AAS treatment and AAS abstinence. Materials and Methods: Twenty (20) adult male Wistar used were divided into four (4) groups, A and B served as the positive and negative control given normal saline and olive oil respectively, C and D was given 120mg/kg/bodyweight oral AAS for 21 days while D served as the 7 days withdrawal group after AAS treatment by evaluating histopathological changes in the liver histology, mucin/ glycogen granules, network of reticulum fibers, liver function enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid peroxidation enzyme malondialdehyde (MDA) and antioxidant enzyme. Results and Discussion: AAS treatment perturbed hepatocellular membrane integrity seen in the increase MDA, AST and ALT activity which caused disruption of the hepatocytes cell integrity attributed to a decline in endogenous SOD. However, AAS withdrawal group gradually reversed AAS mediated heaptocellular pathogenesis associated with progressive elevation of endogenous SOD, decline in MDA and activities of liver function test. Conclusion: AAS mediates hepatic injury through lipid peroxidation and a decline in endogenous antioxidant enzyme, withdrawal of AAS slows down the oxidative damage process when the endogenous antioxidant production increases and mobs off ROS generated by AAS ingested thereby protecting against liver injury and hepato-cellular break down.

Therapeutic Effects of Exosome Therapy and Photobiomodulation Therapy on the Spermatogenesis Arrest in Male Mice After Scrotum Hyperthermia.

Introduction: In men, several factors cause infertility, among which we can mention damage to sperm due to high temperature. So far, various treatments have been proposed for it, but they have not been highly effective. The current study aimed to evaluate the effect of exosome therapy (EXO) and photobiomodulation therapy (PBMT) on spermatogenesis arrest in male mice after scrotum hyperthermia. Methods: In this experimental study, the animals were divided into four groups: control, scrotal hyperthermia, scrotal hyperthermia+EXO (100 μL/d) (mice were treated for 30 days), scrotal hyperthermia+PBMT (laser of 0.03 J/cm2 for 30 seconds/for 30 days). Hyperthermia was induced by exposure to the temperature of 43 °C for 20 minute every day for 5 times. After 6 weeks, the animals were sacrificed. Results: The treated groups showed a significant increase in sperm parameters, as compared to the hyperthermic groups. Moreover, these favorable effects were observed in relation to the volume of testicular tissue, the number of germ cells, Leydig cells and Sertoli cells, and the level of testosterone. Research on antioxidants showed a significant reduction in oxidized glutathione (GSSG) and reactive oxygen species (ROS) in the treatment groups in comparison to the hyperthermia group (P<0.001). Also, there has been a significant increase in the amount of hydrogen peroxide enzyme observed in the hyperthermia group as opposed to the treatment group (P<0.001). Conclusion: These findings show that EXO and PBMT can improve spermatogenesis caused by hyperthermia, reduce ROS and GSSG, and increase glutathione (GSH) and sperm quality.

Decomposition of 2,4-dihalophenols by dehaloperoxidase activity and spontaneous reaction with hydrogen peroxide

The enzyme dehaloperoxidase (DHP) found in the marine worm Amphitrite ornata is capable of enzymatic peroxidation of 2,4-dichlorophenol (DCP) and 2,4-dibromophenol (DBP). There is also at least one parallel oxidative pathway and the major products 2-chloro-1,4-benzoquinone (2-ClQ) and 2-bromo-1,4-benzoquinone (2-BrQ) undergo aspontaneous secondary hydroxylation reaction. The oxidation and hydroxylation reactions have been monitored by UV–visible spectroscopy, High Performance Liquid Chromatography (HPLC), and mass spectrometry. Evidence from time-resolved UV–visible spectroscopy suggests that the hydroxylations of 2-ClQ and 2-BrQ in the presence of hydrogen peroxide (H2O2) are non-enzymatic spontaneous processes approximately ∼10 and ∼ 5 times slower, respectively, than the enzymatic oxidation of DCP or DBP by DHP in identical solvent conditions. The products 2-ClQ and 2-BrQ have λmaxat 255 nm and 260 nm, respectively. Both substrates, DCP and DBP, react to form a parallel product peaked at 240 nm on the same time scale as the formation of 2-ClQ and 2-BrQ. The 240 nm band is not associated with the hydroxylation process, nor is it attributable to the catechol 3,5-dihalobenzene-1,3-diol observed by mass spectrometry. One possible explanation is that muconic acid is formed as a decomposition product, which could follow decomposition either the catechol or hydroxyquinone. These reactions give a more complete understanding of the biodegradation of xenobiotics by the multi-functional hemoglobin, DHP, in Amphitrite ornata. SynopsisThe decomposition of 2,4-dihalophenols catalyzed by dehaloperoxidase was studied by UV–visible spectroscopy, High Performance Liquid Chromatography and Liquid Chromatography-Mass Spectrometry. Spectroscopic evidence suggests two major products, which we propose are 2-halo-1,4-benzoquinone and 2-halomuconic acid. These complementary techniques give a high-level view of the degradation of xenobiotics in marine ecosystems.

Overburdened ferroptotic stress impairs tooth morphogenesis

The role of regulated cell death in organ development, particularly the impact of non-apoptotic cell death, remains largely uncharted. Ferroptosis, a non-apoptotic cell death pathway known for its iron dependence and lethal lipid peroxidation, is currently being rigorously investigated for its pathological functions. The balance between ferroptotic stress (iron and iron-dependent lipid peroxidation) and ferroptosis supervising pathways (anti-lipid peroxidation systems) serves as the key mechanism regulating the activation of ferroptosis. Compared with other forms of regulated necrotic cell death, ferroptosis is critically related to the metabolism of lipid and iron which are also important in organ development. In our study, we examined the role of ferroptosis in organogenesis using an ex vivo tooth germ culture model, investigating the presence and impact of ferroptotic stress on tooth germ development. Our findings revealed that ferroptotic stress increased during tooth development, while the expression of glutathione peroxidase 4 (Gpx4), a crucial anti-lipid peroxidation enzyme, also escalated in dental epithelium/mesenchyme cells. The inhibition of ferroptosis was found to partially rescue erastin-impaired tooth morphogenesis. Our results suggest that while ferroptotic stress is present during tooth organogenesis, its effects are efficaciously controlled by the subsequent upregulation of Gpx4. Notably, an overabundance of ferroptotic stress, as induced by erastin, suppresses tooth morphogenesis.

Overburdened ferroptotic stress impairs tooth morphogenesis.

The role of regulated cell death in organ development, particularly the impact of non-apoptotic cell death, remains largely uncharted. Ferroptosis, a non-apoptotic cell death pathway known for its iron dependence and lethal lipid peroxidation, is currently being rigorously investigated for its pathological functions. The balance between ferroptotic stress (iron and iron-dependent lipid peroxidation) and ferroptosis supervising pathways (anti-lipid peroxidation systems) serves as the key mechanism regulating the activation of ferroptosis. Compared with other forms of regulated necrotic cell death, ferroptosis is critically related to the metabolism of lipid and iron which are also important in organ development. In our study, we examined the role of ferroptosis in organogenesis using an ex vivo tooth germ culture model, investigating the presence and impact of ferroptotic stress on tooth germ development. Our findings revealed that ferroptotic stress increased during tooth development, while the expression of glutathione peroxidase 4 (Gpx4), a crucial anti-lipid peroxidation enzyme, also escalated in dental epithelium/mesenchyme cells. The inhibition of ferroptosis was found to partially rescue erastin-impaired tooth morphogenesis. Our results suggest that while ferroptotic stress is present during tooth organogenesis, its effects are efficaciously controlled by the subsequent upregulation of Gpx4. Notably, an overabundance of ferroptotic stress, as induced by erastin, suppresses tooth morphogenesis.

The Effects of Replacing Fish Meal Protein with Black Soldier Fly Meal and Sodium Butyrate Supplementation on the Growth Performance, Lipid Peroxidation, and Intestinal Villi Status of Jade Perch, Scortum barcoo Fingerlings

This study investigated the effects of different protein sources and butyric acid contents in aquafeed on the growth, survival rate, lipid peroxidation enzymes, and intestinal villi of 7.3 g jade perch, Scortum barcoo. The experimental treatment groups were the whole fish meal protein (FM) group, the FM + butyric acid (FMB) group, the 50% fish meal protein and 50% black soldier fly meal protein (FBM) group, the FBM + butyric acid (FBMB) group, the whole black soldier fly meal protein (BM) group, and the BM + butyric acid (BMB) group. The experimental results showed that the jade perch fed with the FMB feed had a significantly higher weight gain rate and antioxidant enzyme activity than the other treatment groups. The red blood cell count, hemoglobin concentration, and hematocrit contents in the blood of jade perch were not affected by the protein source, but they increased with the addition of butyric acid. The intestinal villi length of the jade perch that were fed diets containing butyric acid were significantly higher than that of the jade perch that were fed diets without butyric acid supplementation. The results of this study show that the addition of butyric acid to a balanced feed composed of protein can contribute to the growth of jade perch.

Fabrication of Polyvinyl Alcohol Doped CuO Thin Films for Improved Amperometric-Non Enzymatic Hydrogen Peroxide Sensing

Fabrication of Polyvinyl Alcohol Doped CuO Thin Films for Improved Amperometric-Non Enzymatic Hydrogen Peroxide Sensing

Different Structures-Similar Effect: Do Substituted 5-(4-Methoxyphenyl)-1H-indoles and 5-(4-Methoxyphenyl)-1H-imidazoles Represent a Common Pharmacophore for Substrate Selective Inhibition of Linoleate Oxygenase Activity of ALOX15?

Mammalian 15-lipoxygenases (ALOX15) are lipid peroxidizing enzymes that exhibit variable functionality in different cancer and inflammation models. The pathophysiological role of linoleic acid- and arachidonic acid-derived ALOX15 metabolites rendered this enzyme a target for pharmacological research. Several indole and imidazole derivatives inhibit the catalytic activity of rabbit ALOX15 in a substrate-specific manner, but the molecular basis for this allosteric inhibition remains unclear. Here, we attempt to define a common pharmacophore, which is critical for this allosteric inhibition. We found that substituted imidazoles induce weaker inhibitory effects when compared with the indole derivatives. In silico docking studies and molecular dynamics simulations using a dimeric allosteric enzyme model, in which the inhibitor occupies the substrate-binding pocket of one monomer, whereas the substrate fatty acid is bound at the catalytic center of another monomer within the ALOX15 dimer, indicated that chemical modification of the core pharmacophore alters the enzyme-inhibitor interactions, inducing a reduced inhibitory potency. In our dimeric ALOX15 model, the structural differences induced by inhibitor binding are translated to the hydrophobic dimerization cluster and affect the structures of enzyme-substrate complexes. These data are of particular importance since substrate-specific inhibition may contribute to elucidation of the putative roles of ALOX15 metabolites derived from different polyunsaturated fatty acids in mammalian pathophysiology.

Scutellarein alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis by chelating iron and interacting with arachidonate 15-lipoxygenase.

Ferroptosis, an iron-dependent cell death characterized by lethal lipid peroxidation, is involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Therefore, ferroptosis inhibition represents an attractive strategy for COPD therapy. Herein, we identified natural flavonoid scutellarein as a potent ferroptosis inhibitor for the first time, and characterized its underlying mechanisms for inhibition of ferroptosis and COPD. In vitro, the anti-ferroptotic activity of scutellarein was investigated through CCK8, real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, flow cytometry, and transmission electron microscope (TEM). In vivo, COPD was induced by lipopolysaccharide (LPS)/cigarette smoke (CS) and assessed by changes in histopathological, inflammatory, and ferroptotic markers. The mechanisms were investigated by RNA-sequencing (RNA-seq), electrospray ionization mass spectra (ESI-MS), local surface plasmon resonance (LSPR), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and molecular dynamics. Our results showed that scutellarein significantly inhibited Ras-selective lethal small molecule (RSL)-3-induced ferroptosis and mitochondria injury in BEAS-2B cells, and ameliorated LPS/CS-induced COPD in mice. Furthermore, scutellarein also repressed RSL-3- or LPS/CS-induced lipid peroxidation, GPX4 down-regulation, and overactivation of Nrf2/HO-1 and JNK/p38 pathways. Mechanistically, scutellarein inhibited RSL-3- or LPS/CS-induced Fe2+ elevation through directly chelating Fe2+ . Moreover, scutellarein bound to the lipid peroxidizing enzyme arachidonate 15-lipoxygenase (ALOX15), which resulted in an unstable state of the catalysis-related Fe2+ chelating cluster. Additionally, ALOX15 overexpression partially abolished scutellarein-mediated anti-ferroptotic activity. Our findings revealed that scutellarein alleviated COPD by inhibiting ferroptosis via directly chelating Fe2+ and interacting with ALOX15, and also highlighted scutellarein as a candidate for the treatment of COPD and other ferroptosis-related diseases.

Monitoring of Defense Enzymes (Phenylalanine Ammonia Lyase and Peroxidase) in Magnaporthe oryzae Infected Leaves after Treatment with Green Synthesized Silver Nanoparticles

Abstract: Objectives: In this study, we focus on the amount of the two defence enzymes phenylalanine ammonia-lyase (PAL) and peroxidase (POX) expressed with regard to the treatment of green synthesized silver nanoparticles. Materials and Methods: The leaf blades were infected with Fungal spores and silver nanoparticles by spraying, and following infection, we estimated the enzyme activity of PAL and POX. The PAL activity is considered by using cinnamic acid as a standard. Results: Our results showed both the PAL and POX enzymes were found to be elevated on infection with spores, and on treatment, the activity was reduced in both cases. There was a significant elevation of PAL (8.937±0.55) in infected leaves, which could be due to infection and on treatment, the enzyme activity was reduced which possibly could be because of the antifungal activity of the synthesised nanoparticles. The POX levels exceeded the control by 417.86%, 807.14% and 921.43% respectively for infected, treatment with AgNPs and treatment with positive control. This confirms the role of the peroxide enzyme in disease control and resistance. Conclusion: This enzyme activity study to our knowledge is the first report done on the infected rice plants with Magnaporthe oryzae and on treatment with silver nanoparticles. This could pave the way to understanding the role of these enzymes in defence activity. Keywords: Magnaporthe oryzae, PAL, POX, Silver Nanoparticles, Defense enzymes

Vitamin D regulates insulin and ameliorates apoptosis and oxidative stress in pancreatic tissues of rats with streptozotocin-induced diabetes

This study was designed to evaluate the potential therapeutic efficacy of vitamin D (Vit D) in averting the harmful effects of type 2 diabetes mellitus (T2D). Forty male Wistar rats were allotted into four groups: (1) the control, (2) Vit D, (3) streptozotocin (STZ), and (4) STZ + Vit D groups. Rats co-treated with Vit D had significantly (p < 0.05) decreased levels of cortisol; proinflammatory cytokines, including interleukin-6 (IL-6); and malondialdehyde (MDA). Meanwhile, the levels of insulin significantly (p < 0.05) increased, whereas the activity of the antioxidant system, including glutathione (GSH), superoxide dismutase (SOD), catalase, and total antioxidant capacity (TAC), significantly (p < 0.05) decreased. Histopathological examination revealed the destruction of beta cells in the islets of Langerhans in rats with diabetes. Meanwhile, immunoexpression revealed an increase in the immunoreactivity of caspase-3 and endothelial nitric oxide synthase and a reduction in the immunoreactivity of insulin in rats with diabetes. In conclusion, Vit D ameliorated the harmful biochemical impact of diabetes mellitus, probably by increasing insulin secretion and sensitivity, ameliorating β-cell function, and decreasing cortisol levels; also, the anti-inflammatory effect of Vit D reduces the number of proinflammatory cytokines (e.g., IL-6) and increases the activity of the antioxidant system, such as GSH, SOD, TAC, and catalase while reducing lipid peroxidation enzymes (e.g., MDA).

Hepatic Oxidative Damages and Glucose Tolerance in Diabetic Rats Exposed to Repeated Oral Doses of Diazinon

Background: Environmental pollutants including organophosphate insecticides impair glucose metabolism by altering hepatic oxidation and play an important role in the development of diabetes and its complications. The aim of this study was to assess the impacts of repeated oral doses of Diazinon, an organophosphate insecticide, which is known to impair the glucose metabolism and its tolerance through oxidative stress in the rat liver. Methods: Diabetes was induced in rats by a single dose of freshly prepared Streptozotocin at 60 mg/kg. Both normal and diabetic rats were exposed to daily oral Diazinon at 20 mg/kg for 21 days. Subsequently, the effects on the rats’ liver were assessed by glucose tolerance test, histopathology examinations and antioxidant capacity measurement. Results: The glucose tolerance tests showed impairment in the non-diabetic rats exposed to Diazinon, while the difference in glucose tolerance between the diabetic rats treated with or without Diazinon was not significant. Diazinon in diabetic rats caused greater histopathological changes along with significant elevations in the lipid peroxidation and antioxidant enzymes, including superoxide dismutase and catalase in the liver tissue. Conclusion: Subacute exposure to Diazinon exacerbated hepatotoxicity by inducing oxidative stress in diabetic rats. The superoxide dismutase and catalase activities increased due to the oxidative damages in rats’ liver caused by Diazinon.

Inhibitory effect of Solanum xanthocarpum on the growth of KB human oral cancer cell line in vitro through ROS-induced mitochondrial pathway

The aim of the present study was to investigate the effect of Solanum xanthocarpum on KB human oral cancer cells by analyzing its anti-proliferative and apoptotic properties as well as its inhibitory effect on cell adhesion. In this study, the leaves extract of S. xanthocarpum was prepared using the maceration method. Cytotoxic effect of different doses of the S. xanthocarpum extract was assessed using MTT assay. Measurements of reactive oxygen species (ROS), lipid peroxidation and antioxidant enzymes were also performed. In addition, we also studied the impacts of S. xanthocarpum on the apoptosis and mitochondrial membrane potential of KB cells. Determination of antioxidant enzymes and lipid peroxidation was performed using biochemical methods. The S. xanthocarpum showed cytotoxic activity against KB cells with IC50 (200 μg/mL). Besides, DCFH-DA staining and acridine orange/ethidium bromide staining results demonstrated that S. xanthocarpum induced the generation of ROS and apoptosis in KB cells, respectively. Based on the Rh-123 staining results, S. xanthocarpum decreased mitochondrial depolarization in KB cells. Furthermore, the S. xanthocarpum treatment contributed to increased lipid peroxidation, accompanied by reduced activities of superoxide dismutase and catalase, as well as decreased glutathione content. Taken together, these findings indicate that S. xanthocarpum extract might comprise bioactive compounds of therapeutic significance, which can inhibit the growth of KB cells.

Inhibitory effects of chitosan grafted chlorogenic acid on antioxidase activity, and lipid and protein oxidation of sea bass (Lateolabrax japonicus) fillets stored at 4 °C.

Sea bass (Lateolabrax japonicus), a marine fish, is prone to spoilage due to its high nutritional value. Preservatives are commonly used for storage for the production of fish fillets. In this work, chitosan (CS) was grafted onto chlorogenic acid (CA) to obtain a new preservative, chitosan grafted chlorogenic acid (CS-g-CA), which could enhance the biochemical properties of chitosan and obtain better antibacterial and antibacterial properties. This study therefore investigated the inhibitory effects of CS-g-CA on antioxidant enzyme activity, and lipid and protein oxidation of sea bass fillets stored at 4 °C. Compared with the control group on day 9, the activity of 63% catalase (CAT), 78% superoxide diamidase (SOD), 73% glutathione peroxide enzyme (GSH-Px) and 60% DPPH scavenging activity was retained by CS-g-CA treatment. Changes in thiobarbituric acid (TBA) and conjugated diene (CD) values were delayed by CS-g-CA treatment. The use of CS-g-CA retards protein oxidation by inhibiting the formation of free amino acid and carbonyl groups, and maintaining a higher sulfhydryl content. Regarding myofibril degradation, CS-g-CA could maintain protein secondary structure by increasing the ratio of α-helices. Chitosan-grafted chlorogenic acid could protect the activity of antioxidant enzymes and inhibit lipid oxidation by slowing down the production of lipid oxidation products. It also delayed protein oxidation by inhibiting oxidation product generation and stabilizing protein structure. It could therefore be used as a promising preservative for seafood. © 2022 Society of Chemical Industry.

Melatonin evaluation of obesity women during heavy aerobic exercise in Kirkuk university

The impacted of heavy aerobic exercise on lipid peroxidation during determination the Malondialdehyde (MDA) level has been examined in young training obesity women under melatonin bellowing the free radical formation ;So this study aimed to objective the incurring role of melatonin for lipid peroxidation by regulation hepatic enzyme and lipid profile administration. Methods: This study done faculty of physical Education, Kirkuk university at three months from January to march-2022. Result: The study included healthy young women has body mass index(BMI) ranged more than30kg/m2 ,age ranged between18-35years.Total includingat 50 healthy young women (25 trained and 25 non training healthy) performed an aerobic cycling exercise at threshold for about 2 hours daily untile40days. The venous blood sample was drawing (pre and post exercise finishing) and analyzing for measuring malondialdehyde(MDA) , glutathione(GSH) ,melatonin ,nitric oxide(NO) ,hepatic enzymes are(lactate dehydrogenase-LDH, aspartate-AST, alanine aminotransferase-ALT ,lipid profile which is low density lipoprotein-cholesterol(LDL-c),high density lipoprotein-cholesterol(HDL-c),triglyceride(TG) and glucose in the serum ,so the (MDA) level in obese women that aged more than25 years is(5.93+1.68) mmol/l than control groups(3.97+0.14) mmol/l, but maximum level of melatonin in women aged less than18years is(23.81+5.61) mmol/l than control groups(23.95+0.15)mmol/l; therefore,the level of Nitric oxide in women age ranged more than25years(127.67+7.85) mmol/l is highly than the control groups(12.75+2.24)mmol/l, because the level of hepatic enzyme(ALP)(97.11+4.22)IU/l in women aged more than25years,while the level of(ALT)in women aged less than25years is significantly decreased(35.61+9.91)IU/l ;therefore ,the level of LDL-c is(4.8+0.11)mmol/l after exercise less than control groups(4.97+0.11) mmol/l ,while the level of HDL-c in control groups is(2.32+0.11) mmol/l and gradually increased after exercise(1.93+0.12) mmol/l when the glucose concentration is(193+0.12) mmol/l before exercise. Conclusion: The development of obesity lead to increased lipid peroxidation and elevation hepatic enzyme for controlling of oxidative stress in the tissue by melatonin attenuated reactive oxygen species that releasing in the obese healthy women after optimal time of heavy aerobic exercise.

Viscosity-dependent photocatalysis triggers ferroptosis and Type-I photodynamic therapy to kill drug-resistant tumors

Treating complex drug-resistant tumors is a challenge in clinical practice. Ferroptosis, a unique form of programmed cell death, is a promising therapeutic strategy to address such tumors. We present a method by which a photodynamic and photocatalytic synergy triggered ferroptosis to kill drug resistant tumors via a triarylmethane/CF3SO2Na-based liposomal nanosystem (CF3-CVJ NPs). Under 630-nm light irradiation, the type-I photosensitizer, CVJ, catalyzed the persistent conversion of O2 to ∙O2− and CF3SO2Na to ·CF3 and SO2. Thereafter, the generated ·CF3 efficiently oxidized lipids to lipid peroxides together with ∙O2− and induced ferroptosis in drug-resistant cells, while SO2 inhibited the catabolic lipid peroxidation enzyme glutathione peroxidase 4. Our results revealed that photosensitized reactions upregulated pro-apoptotic proteins through mitochondrial damage, resulting in the reactivation of drug-resistant tumor cell apoptosis. The efflux of the photosensitizer, CVJ, was prevented by reducing efflux protein expression as well as mitochondrial adenosine triphosphate production. Overall, utilizing arginine-glycine-aspartic acid (RGD)-tumor targeting and the different viscosities between tumor cells and normal cells, is our new strategy for treating drug-resistant tumors, with excellent selectivity and efficiency.