Alterations In Oxidative Status Research Articles

PSVI-14 Effects of poor maternal nutrition during gestation on first generation offspring oxidative status in skeletal muscle

Abstract Poor maternal nutrition (restricted- and over-nutrition) during gestation negatively impacts offspring pre- and post-natal growth. Previous work has identified decreased muscle mass and increased adiposity, leading to poor quantity and quality of animal protein products. Alterations in oxidative status, such as the imbalance of antioxidant activity and the production of free radicals, can result in oxidative stress damaging lipid membranes, proteins, and DNA. Changes in oxidative status may contribute to the poor growth outcomes observed in offspring from poorly nourished dams. Therefore, the objective of this research was to determine the effects of poor maternal nutrition during gestation on the oxidative status in offspring skeletal muscle in sheep. We hypothesized that offspring of restricted- and over-fed ewes would have decreased antioxidant activity and increased products of oxidative stress in skeletal muscle. To test this hypothesis, multiparous Dorset ewes (n = 46) pregnant with twins were fed 100% (CON), 60% (RES), or 140% (OVER) of total nutrient requirements (NRC) from d 30 of gestation until parturition. Following parturition, ewes were fed a control diet throughout lactation. At d 282 of age semitendinosus (STN) samples were collected from rams at necropsy, and at d 284 of age muscle biopsies from STN were collected from ewes. Data were analyzed in SAS using PROC MIXED with fixed effects of maternal diet and offspring sex. Data were considered significant at P ≤ 0.05. The activity of the endogenous antioxidant superoxide dismutase (SOD) was decreased by 45% and 33% in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). Offspring sex did not alter STN SOD activity (P = 0.35). Muscle glutathione peroxidase (GPx) activity was decreased in RES offspring by 20% compared with CON (P ≤ 0.04), but neither differed from OVER offspring (P ≥ 0.24). Ewes had 34% greater GPx activity compared with rams (P < 0.0001). Offspring from RES and OVER ewes had 77% and 87% greater concentrations of malondialdehyde (MDA), a marker of lipid peroxidation, when compared with CON (P < 0.0001). Ewes had 29% greater MDA concentrations compared with rams (P = 0.05). Protein carbonyl (PC), a marker of protein oxidation, concentrations were 36% and 38% greater in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). The decrease in antioxidant activities and increase in products of protein and lipid oxidation in offspring from poorly nourished dams suggests dysregulation in skeletal muscle oxidative status that may contribute to the negative consequences observed in offspring. Future work should focus on determining the mechanistic role of skeletal muscle oxidative stress in the decreased quantity and quality of animal protein products and identifying potential strategies to mitigate alterations in oxidative status as a result of poor maternal nutrition during gestation.

Aged polyethylene microplastics and glyphosate-based herbicide co-exposure toxicity in Pacific white shrimp (Litopenaeus vannamei)

Microplastics and glyphosate-based herbicides (GBHs) unavoidably contaminate aquatic environments, yet their combined effect on aquatic organisms has been scarcely investigated. We present a short-term study on individual and combined effects of aged polyethylene (PE) microplastics and GBH exposures at environmentally relevant concentrations on oxidative damage, antioxidant responses, immune parameters, and hepatopancreas histology in shrimp (Litopenaeus vannamei). In addition, acetylcholinesterase (AChE) was evaluated as a biomarker of GBH exposure. After 96 hours of exposure, individual PE microplastic exposure slightly influenced oxidative status, immune parameters, and histology. Decreases in AChE concentration and alterations in oxidative status, immunity, and cell population in hepatopancreas were observed in single GBH-exposed shrimp. The combinations of aged PE microplastics and GBH induced some changes that differed from individual GBH exposures. For instance, some alterations implied that the presence of aged PE microplastics may alter GBH toxicity to L. vannamei (AChE concentration and some expressions of immune-related genes). In conclusion, our results suggest that single exposure of aged PE microplastics at environmental concentration may slightly affect the health of L. vannamei and that aged PE microplastics are likely to modify the toxicity of other co-exposed chemicals.

Does the anesthetic tricaine methanesulfonate (MS-222) distort oxidative status parameters in tadpoles?

The effect of anesthesia/euthanasia with ethyl 3-aminobenzoate methanesulfonate (MS-222) on the oxidative status of Hyla arborea tadpoles was examined to determine whether the use of the anesthetic can confound the experimental results of the oxidative stress-based investigation. The experiment was conducted on two groups of tadpoles reared at different temperatures to produce differences in antioxidant capacity between the groups. After development at different temperatures (20 °C and 25 °C), the animals were exposed to different concentrations of MS-222 (0, 0.1, 1, and 5 g/L) for 15 min. The higher temperature decreased catalase activity, glutathione and protein carbonyl levels and increased glutathione reductase activity. The glutathione level and glutathione/thiol-related parameters were significantly changed after MS-222 exposure. However, individuals from the different temperature groups responded differently to the tested anesthetic, pointing to the possible influence of the initial levels of antioxidant capacity. The analysis of the interaction between the factors (temperature and MS-222) confirmed that the anesthetic can confound the results regarding the effects of temperature on the oxidative status parameters. The concentration of 0.1 g/L MS-222 had the lowest influence on the alterations in oxidative status and the results of the effect of temperature. A brief review of the current literature on the use of MS-222 in tadpoles made clear the absence of precise information on anesthetic concentration and exposure time. Similar studies should be repeated and extended to other amphibian species and other factors of interest to provide better guidance on tadpole anesthesia/euthanasia for future experiments that consider oxidative status parameters.

Diosmin alleviates doxorubicin-induced chemobrain in rats via inhibition of oxido-inflammation, apoptosis and modulation of autophagy

Background/aimDoxorubicin (DOX) is a highly effective chemotherapy medicine commonly used to treat breast cancer; yet, despite its clinical efficacy, it usually causes chemobrain. As a result, we investigated the neuroprotective effects of Diosmin (DIOS) on DOX-induced chemobrain in male rat brains. Animals and methodsIn the experimental protocol, Rats were divided into 4 groups: group I received solvent and saline for 56 days, group II received Dios and a concomitant dose of saline for 56 days, group III received DOX intraperitoneally on 7th, 14th, 21st, 28th, 35th, 42nd, 49th and 56th days, and Group IV received DIOS (40 mg/kg P.O.) for 56 days and DOX was administered one hour after DIOS oral administration. The novel-object recognition memory test (NORT) was used to assess non-spatial memory function. Following that, brain neurochemical status were assessed. ResultsDIOS increased cognitive performance in DOX-treated rats by enhancing exploration of unfamiliar objects. DIOS protects the brain from DOX-mediated alterations in oxidative status, as well as brain metabolic enzyme indicators. It also decreased MMP-6, IL-6, IL-β1, TNF-α and COX-2 expression, reduced apoptotic markers levels, boosted mTOR protein levels, lowered beclin-1, restored brain metabolic enzyme activities, increased neurotransmitter as well as cathepsin levels, and avoided the rise in α-synuclein and PON1 enzyme activity. ConclusionIn conclusion, DIOS protects rats' brains against DOX-induced chemobrain via oxidative stress inhibition, autophagy modulation, and down-regulation of inflammatory and apoptotic markers.

Motility, oxidative status and morphology of frozen-thawed bovine semen are not impacted by fatty acid exposure invitro.

While sperm migrate within the reproductive tract of cows experiencing negative energy balance (NEB), they come into contact with elevated concentrations of non-esterified fatty acids (NEFA). For this reason, this study aimed to investigate the effects of three different NEFA - palmitic acid (PA), stearic acid (SA), and oleic acid (OA) - on bovine sperm motility, kinetic parameters, oxidative status, and morphology. Frozen thawed semen samples from Bos taurus bulls were incubated with varying concentrations of each fatty acid, and the sperm's characteristics were analysed at different time points. Computer-Assisted Sperm Analysis (CASA) was employed to assess sperm motility and kinetic parameters. Concurrently, the production of the reactive oxygen species (ROS) and total antioxidant capacity were measured to determine the oxidative status. Additionally, sperm morphology was evaluated. In Experiment 1, different concentrations of PA did not show significant effects on total motility, progressive motility, or any kinetic parameters analysed. Similarly, PA did not have a significant impact on the oxidative status or sperm morphology. In Experiment 2, SA at various concentrations did not lead to significant changes in total motility, progressive motility, or any kinetic parameters evaluated. Furthermore, SA did not affect oxidative status or sperm morphology. In Experiment 3, the concentrations of OA used did not result in significant changes in total motility, progressive motility, or any kinetic parameters studied. Likewise, OA did not induce any alterations in oxidative status or sperm morphology. Overall, the results from all three experiments indicate that PA, SA and OA, at the invitro conditions and tested concentrations, do not exert detrimental effects on bovine sperm function and morphology. These results provide insights that contribute to our understanding of how fatty acids can impact the reduction of fertility rates in cows facing NEB. This, in turn, lays the foundation for additional critical investigations in this area. Further studies are necessary to validate these findings invivo.

446 The Effects of Maternal Diet During Gestation on Oxidative Status of Offspring

Abstract Poor maternal nutrition during gestation is common in livestock production and includes both nutrient restriction and over-nutrition. Poor maternal nutrition affects offspring pre- and post-natal growth including decreases in muscularity and increases in adiposity which results in poor quantity and quality of animal products. Oxidative stress, when free radicals exceed the capacity of antioxidants, damages lipid membranes, proteins, and DNA. Oxidative stress may contribute to the poor growth outcomes observed in offspring from poorly nourished dams. Therefore, the objective of this research was to determine the effects of poor maternal nutrition during gestation on offspring circulating oxidative status in sheep. We hypothesized that offspring of restricted- and over-fed ewes would have an altered oxidative status in circulation. To test this hypothesis, multiparous Dorset ewes (n = 45) pregnant with twins were fed 100% (CON), 60% (RES), or 140% (OVER) of National Research Council requirements from d 30 of gestation until parturition. At parturition, ewes were fed a control diet such that the nutritional insult only occurred during gestation. Blood samples were collected from offspring by jugular venipuncture at d 112 and d 224 of age to evaluate oxidative status in circulation. Data were analyzed in SAS 9.4 using PROC MIXED with fixed effects of offspring sex and maternal diet with sampling timepoint as repeated measure. Data were considered significant at P < 0.05. In offspring plasma, superoxide dismutase, an endogenous antioxidant, activity was 17% greater in CON offspring compared with RES and OVER (P ≤ 0.04). Malondialdehyde (MDA), a marker of lipid peroxidation, concentration was not different at d 112 but RES animals had 10% lesser concentration of MDA than CON at d 224 (P ≤ 0.02). Protein carbonyl (PC), a marker of protein oxidation, concentration was 9% greater in CON animals than RES and OVER (P = 0.01). Additionally, PC concentrations were 19% greater at d 224 compared with d 112 (P ≤ 0.001). These results indicate that at the chosen timepoints, RES and OVER offspring had less antioxidant activity but also less indication of oxidative damage. Overall, the alterations in antioxidant activity and oxidative damage suggest dysregulation in circulating oxidative status that may contribute to the negative consequences of poor maternal nutrition during gestation. Future work should focus on the impacts of poor maternal nutrition on oxidative stress in muscle.

Toxicity mechanisms of biomass burning aerosols in in vitro hepatic steatosis models

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that contributes to the global rise in liver-related morbidity and mortality. Wood tar (WT) aerosols are a significant fraction of carbonaceous aerosol originating from biomass smoldering, contributing to air pollution particles smaller than 2.5 mm (PM2.5). Mechanistic biological associations exist between exposure to PM2.5 and increased NAFLD phenotypes in both cell and animal models. Therefore, this study examines whether an existing NAFLD-like condition can enhance the biological susceptibility of liver cells exposed to air pollution in the form of WT material. Liver cells were incubated with lauric or oleic acid (LA, OA, respectively) for 24 h to accumulate lipids and served as an in vitro hepatic steatosis model. When exposed to 0.02 or 0.2 g/L water-soluble WT aerosols, both steatosis model cells showed increased cell death compared to the control cells (blank-treated cells with or without pre-incubation with LA or OA) or compared to WT-treated cells without pre-incubation with LA or OA. Furthermore, alterations in oxidative status included variations in reactive oxygen species (ROS) levels, elevated levels of lipid peroxidation adducts, and decreased expression of antioxidant genes associated with the NRF2 transcription factor. In addition, steatosis model cells exposed to WT had a higher degree of DNA damage than the control cells (blank-treated cells with or without pre-incubation with LA or OA). These results support a possible systemic effect through the direct inflammatory and oxidative stress response following exposure to water-soluble WT on liver cells, especially those predisposed to fatty liver. Furthermore, the liver steatosis model can be influenced by the type of fatty acid used; increased adverse effects of WT on metabolic dysregulation were observed in the LA model to a higher extent compared to the OA model.

The Emerging Role of Heat Shock Factor 1 (HSF1) and Heat Shock Proteins (HSPs) in Ferroptosis.

Cells employ a well-preserved physiological stress response mechanism, termed the heat shock response, to activate a certain type of molecular chaperone called heat shock proteins (HSPs). HSPs are activated by transcriptional activators of heat shock genes known as heat shock factors (HSFs). These molecular chaperones are categorized as the HSP70 superfamily, which includes HSPA (HSP70) and HSPH (HSP110) families; the DNAJ (HSP40) family; the HSPB family (small heat shock proteins (sHSPs)); chaperonins and chaperonin-like proteins; and other heat-inducible protein families. HSPs play a critical role in sustaining proteostasis and protecting cells against stressful stimuli. HSPs participate in folding newly synthesized proteins, holding folded proteins in their native conformation, preventing protein misfolding and accumulation, and degrading denatured proteins. Ferroptosis is a recently identified type of oxidative iron-dependent cell demise. It was coined recently in 2012 by Stockwell Lab members, who described a special kind of cell death induced by erastin or RSL3. Ferroptosis is characterized by alterations in oxidative status resulting from iron accumulation, increased oxidative stress, and lipid peroxidation, which are mediated by enzymatic and non-enzymatic pathways. The process of ferroptotic cell death is regulated at multiple, and it is involved in several pathophysiological conditions. Much research has emerged in recent years demonstrating the involvement of HSPs and their regulator heat shock factor 1 (HSF1) in ferroptosis regulation. Understanding the machinery controlling HSF1 and HSPs in ferroptosis can be employed in developing therapeutic interventions for ferroptosis occurrence in a number of pathological conditions. Therefore, this review comprehensively summarized the basic characteristics of ferroptosis and the regulatory functions of HSF1 and HSPs in ferroptosis.

Multi-biomarker approach and IBR index to evaluate the effects of bisphenol A on embryonic stages of zebrafish (Danio rerio)

This study assessed the effects of Bisphenol A in embryonic stages of zebrafish, applying an IBR multi-biomarker approach that included alterations in growth and oxidative status and relates it with the expression of Nrf1, Nrf2, Wnt3a, Wnt8a, COX-2, Qdpra, and DKK1 genes. For this purpose, we exposed zebrafish embryos to eight environmentally relevant concentrations of BPA (220, 380, 540, 700, 860, 1180, 1340, and 1500 ng L−1) until 96 h post-fertilization. Our results show that BPA induces several malformations in embryos (developmental delay, hypopigmentation, tail malformations, and on), leading to their death. The LC50, EC50 of malformations, and teratogenic index (TI) were 1234.60 ng L−1, 987.77 ng L−1, and 1.25, respectively; thus, this emerging contaminant is teratogenic. Regarding oxidative stress and gene expression, we demonstrated BPA altered oxidative status and the gene expression in embryos of Danio rerio.

Thiol/disulfide homeostasis and oxidant status in children with congenital heart disease

Abstract Objectives This article aims to explain the altered oxidative status and thiol/disulfide homeostasis before and after surgery in children with congenital heart disease (CHD). Methods Blood samples were taken from the patients (n=50) before the operation (baseline), at the 1st hour, and at the 24th hour after the operation. Thiol-disulfide levels, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), myeloperoxidase (MPO), ceruloplasmin, albumin, ischemia-modified albumin (IMA), and prolidase activities of all samples were measured. Pre-operative oxygen saturation (SaO2) values and neutrophil/lymphocyte ratios (NLR) were also measured. Results Before the operation, TOS, OSI, MPO, ceruloplasmin, IMA, NRL, and disulfide levels were higher in the cyanotic group than in the acyanotic group. When the indicated three different time points were compared, the TOS, OSI levels, and MPO activities of the 24th hour were significantly lower than the baseline and 1st hour. In comparison, ceruloplasmin levels of 1st hour were significantly higher than of the baseline and 24th hour. Native thiol and total thiol levels in the baseline group were significantly lower than in the 1st and 24th hours. Disulfide levels of the 24th hour were significantly lower than of the baseline. Conclusions The operation leads to changes in the thiol-disulfide balance and oxidant status in CHD.

THE EFFECT OF 7-DAY HIGH-SALT DIET ON SERUM ANTIOXIDANT ENZYMES PROTEIN CONCENTRATIONS: DOES ANTIOXIDANT VITAMINS SUPPLEMENTATION MATTER?

Abstract Objective: It is well documented that high salt (HS) diet causes increased oxidative stress. Present study aimed to test the effect of 7-day HS diet on serum protein concentrations of Cu/Zn superoxide dismutase (Cu/Zn SOD), glutathione peroxidase 1 (GPx1) and catalase, and to examine whether the oral supplementation of non-specific ROS scavengers (vitamin C and vitamin E) during 7-day HS loading will change serum protein concentrations of these antioxidant enzymes in otherwise healthy normotensive individuals. Design and method: 40 young healthy individuals (20 men and 20 women, age ranged 18–24) were assigned to a 7-day low-salt diet (<3.5 g salt/day) followed by a 7-day HS diet (∼14 g salt/day) without (HS group) or with the daily supplementation of vitamins C (1000 mg) and E (800 IU) (HS + C + E group). Blood pressure (BP) and heart rate (HR) were measured at each study visit. Serum protein concentrations of Cu/Zn SOD, GPx1 and catalase were measured by commercially available ELISA kits before and after diet protocols. Results: BP and HR were not significantly different in both, HS and HS + C + E groups compared to LS diet. Changes in calculated daily salt intake from 24 h sodium excretion confirmed that participants conformed to the diet protocols. Serum protein concentration of Cu/Zn SOD and GPx1 were not significantly changed following both HS or HS + C + E diet compared to measurement following LS diet. 7-day HS diet significantly decreased serum catalase concentration in HS group compared to LS diet (catalase pg/ml LS 347 ± 495 vs. HS 261 ± 462, P < 0.05), while catalase concentration was similar after LS and following 7 days of HS + C + E diet (catalase pg/ml LS 249 ± 375 vs. HS + C + E 186 ± 349, P > 0.05). Conclusions: The results of this study suggest that disturbing the activity of antioxidative defense itself (decreased serum catalase concentration) could potentially contribute to the altered oxidative status in healthy individuals on a HS diet, which could be prevented by intake of antioxidant vitamins C and E during HS diet.

Integrative Clinical, Molecular, and Computational Analysis Identify Novel Biomarkers and Differential Profiles of Anti-TNF Response in Rheumatoid Arthritis.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients.Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions.Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort.Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

The heart of the adult goldfish Carassius auratus as a target of Bisphenol A: a multifaceted analysis

Bisphenol A (BPA) is a contaminant whose presence in aquatic environments is increasing. In fish embryos and larvae, it severely affects cardiac development; however, its influence on the heart function of adult fish has been scarcely analyzed. This study investigated the effects of the invivo exposure to BPA on heart physiology, morphology, and oxidative balance in the goldfish Carassius auratus. Adult fish were exposed for 4 and 10 days to two BPA concentrations (10μM and 25μM). Exvivo working heart preparations showed that high concentrations of BPA negatively affected cardiac hemodynamics, as revealed by an impaired Frank-Starling response. This was paralleled by increased cardio-somatic indices and by myocardial structural changes. An altered oxidative status and a modulation of stress (HSPs) and pro-apoptotic (Bax and Cytochrome C) proteins expression were also observed in the heart of animals exposed to BPA, with detrimental effects at the highest concentration and the longest exposure time. Results suggest that, in the adult goldfish, BPA may induce stressful conditions to the heart with time- and concentration-dependent deleterious morpho-functional alterations.

Mechanisms of lung toxicity induced by biomass burning aerosols

BackgroundCarbonaceous aerosols emitted from indoor and outdoor biomass burning are major risk factors contributing to the global burden of disease. Wood tar aerosols, namely, tar ball particles, compose a substantial fraction of carbonaceous emissions, especially from biomass smoldering. However, their health-related impacts and toxicity are still not well known. This study investigated the toxicity of the water-soluble fraction of pyrolyzed wood tar aerosols in exposed mice and lung epithelial cells.ResultsMice exposed to water-soluble wood tar aerosols showed increased inflammatory and oxidative stress responses. Bronchial epithelial cells exposed to the same water-soluble wood tar aerosols showed increased cell death with apoptotic characteristics. Alterations in oxidative status, including changes in reactive oxygen species (ROS) levels and reductions in the expression of antioxidant genes related to the transcription factor Nrf2, were observed and were confirmed by increased levels of MDA, a lipid peroxidation adduct. Damage to mitochondria was observed as an early event responsible for the aforementioned changes.ConclusionsThe toxicity and health effect-related mechanisms of water-soluble wood tar were investigated for the first time in the context of biomass burning. Wood tar particles may account for major responses such as cell death, oxidative stress, supression of protection mechnaisms and mitochondrial damaged cause by expsoure to biomass burning aerosols.

Localization dependent sensitivity of cerebral Na,K-ATPase to irradiation induced oxidative imbalance in rats.

Na,K-ATPase represents the key enzyme maintaining the ionic gradient across plasma membrane. It was documented that in directly irradiated organs the activity of this enzyme is decreased. The aim of present study was to clarify the remote effect of irradiation in mediastinal area on the activity of the Na,K-ATPase in selected brain regions in rats. Ionizing radiation in single dose 25 Gy induced alterations in oxidative status of blood plasma. Irradiation also decreased the activity of the Na,K-ATPase in cerebral cortex. Measurements of kinetic properties of the enzyme dependently on the concentration of energy substrate ATP or cofactor Na+ indicated that the lowered enzyme activity is probably a consequence of decreased number of active molecules of the enzyme, as suggested by lowered Vmax values (by 13 - 14%). Immunoblot analysis revealed that this effect is connected namely to decreased presence of α2 and α3 subunits (by 25% and 30% respectively). Considering the current concepts about involvement of the malfunction of α2 α3 subunits in development of primary brain dysfunctions, it may be hypothesized that the lowered functionality of those subunits of Na,K-ATPase may represent a predisposition to neurodegenerative disorders after irradiation. The observed effect seems to be localization dependent as the enzyme in cerebellum resisted to irradiation.

Unraveling the Role of Melatonin/Quercetin in Attenuating the Metabolic and Bone Turnover Alternations in Iron Treated-Ovariectomized Female Rats

AbstractBackground: Iron accumulation is involved in many of postmenopausal associated disorders, like osteoporosis.Aim of Study: This study was designed to evaluate the possible role of iron accumulation in deteriorating the ova-riectomy-induced metabolic and bone remodeling alterations with the possible protective effect of melatonin and quercetin in this respect.Material and Methods: 40 female albino rats were divided into 5 equal groups, 8 rats each; Group 1: Control sham operated group, received intraperitoneal injections of normal saline, 3 times/week after sham operations, Group 2: Ovariec-tomized (OVX) group, received the same saline treatments after bilateral ovariectomy, Group 3: Iron treated-OVX group (F-OVX), received intraperitoneal injections of 0.04g/kg ferric ammonium citrate 3 times a week after bilateral ovariectomy, Group 4: Melatonin + iron treated-OVX group (MF-OVX), received subcutaneous melatonin injections (10mg/kg) daily after bilateral ovariectomy, Group 5: Quercetin + iron treated-OVX group (QF-OVX), received intraperitoneal quercetin injection of 10mg/kg/day after bilateral ovariectomy.At the end of the experimental regimen (4 weeks), blood samples were collected and centrifuged, the obtaining serum was used for determination of iron, ferritin, Malondialdehyde (MDA), Total Antioxidant Capacity (TAC) glucose, insulin and insulin resistance (using HOMA-IR equation). Moreover, the serum Total Cholesterol (TC), High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol (LDL-C) and Triglycerides (TG) were assayed along with bone turnover markers including; serum Osteocalcin (OC), Bone Specific Alkaline Phosphatase (BALP) Cross-linked Carboxy-terminal telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Further-more, livers were removed for determination of liver iron, MDA and TAC levels.Results: Iron treatment in OVX rats further exacerbated the ovariectomy induced alterations in oxidative status, indi-cated by increased MDA and decreased TAC in both serum and liver tissue, metabolic status, indicated by significantly elevated serum TC, LDL-C, TG, glucose and HOMA-IR levels, and bone turnover status, indicated by significant decrease in serum markers of bone formation (OC, BALP) and increase in those of bone resorption (CTX-I, TRACP5b), in F-OVX group compared to OVX group. On the other hand, treatment of F-OVX rats with either melatonin or quercetin significantly mitigated all these alterations, which was in concomitance with improvement of the iron status indicated by significant decrease in serum and liver iron along with serum ferritin levels, in MF-OVX and QF-OVX groups com-pared to F-OVX group.Conclusion: Melatonin and quercetin improved the met-abolic and bone turnover alternations, induced by iron accu-mulation in treated F-OVX rats, possibly via their iron chelat-ing, antioxidant, insulin sensitizing, hypolipidemic and anti-osteoporotic effects, as recorded in this rat model.

Reduced oxidative stress increases acute cold stress tolerance in zebrafish

Cold stress is a major threat to fish in both nature and aquaculture, and can induce oxidative stress in various fish. While the exact role of oxidative stress in cold-caused mortality is still unknown. The purpose of the present study was to evaluate the effects of oxidative stress on cold tolerance in fish and verify whether changing oxidative status could affect cold tolerance. We firstly demonstrated that acute cold exposure induced high oxidative stress in zebrafish liver, which may lead to mortality. Then we performed in vivo and in vitro experiments to determine the effects of the altered oxidative status on cold tolerance in zebrafish and zebrafish liver cell line (ZFL), respectively. In the in vivo study, the zebrafish which were fed with α-lipoic acid or reduced glutathione had lower cold-caused oxidative stress and tissues damage, and showed higher cold tolerance. In the experiment using zebrafish cells, increasing oxidative stress by H2O2 decreased the cellular cold tolerance, and the cold tolerance was partly recovered when oxidative stress was reduced by the addition of Vitamin C (VC). Taken together, we conclude that the reduction of oxidative stress increases cold tolerance in fish.

Combined Consumption of Beef-Based Cooked Mince and Sucrose Stimulates Oxidative Stress, Cardiac Hypertrophy, and Colonic Outgrowth of Desulfovibrionaceae in Rats.

High red meat and sucrose consumption increases the epidemiological risk for chronic diseases. Mechanistic hypotheses include alterations in oxidative status, gut microbiome, fat deposition, and low-grade inflammation. For 2 weeks, 40 rats consumed a diet high in white or red meat (chicken-based or beef-based cooked mince, respectively), and containing corn starch or sucrose in a 2 × 2 factorial design. Lard was mixed with lean chicken or beef to obtain comparable dietary fatty acid profiles. Beef (vs chicken)-fed rats had higher lipid oxidation products (malondialdehyde, 4-hydroxy-2-nonenal, and hexanal) in stomach content and blood, and lower blood glutathione. Sucrose (vs corn starch)-fed rats showed increased blood lipid oxidation products and glutathione peroxidase activity, higher liver weight and malondialdehyde concentrations, and mesenterial and retroperitoneal fat accumulation. Beef-sucrose-fed rats had increased cardiac weight, suggesting pathophysiological effects on the cardiovascular system. The colonic microbiome of beef-sucrose-fed rats showed an outgrowth of the sulfate-reducing family of the Desulfovibrionaceae, and lower abundance of the Lactobacillus genus, indicating intestinal dysbiosis. Blood C-reactive protein, a marker for inflammation, was not different among groups. Consumption of a cooked beef-based meat product with sucrose increased oxidative stress parameters and promoted cardiac hypertrophy and intestinal dysbiosis.

Protective effect of irbesartan against doxorubicin-induced nephrotoxicity in rats: implication of AMPK, PI3K/Akt, and mTOR signaling pathways.

Nephrotoxicity is one of the serious undesirable effects related to doxorubicin (DOX). Herein, we have investigated the potential protective effect of irbesartan (IRB) against chronic nephrotoxicity induced by DOX, and the implication of different mechanistic pathways underlying these effects. Rats were treated with either DOX (2.5 mg/kg i.p., 3 times/week) for 2 weeks, and (or) IRB (40 mg/kg, daily) for 3 weeks. IRB prohibited nephrotoxicity induced by DOX, which was evident by the increase in blood urea nitrogen and creatinine levels and histopathological changes. IRB improved DOX-induced alterations in oxidative status by diminishing lipid peroxidation and upregulating the antioxidant enzymes. Also, upon DOX treatment, the renal expression of tumor necrosis factor-α, interleukin-6, and caspase-3 were significantly increased; IRB diminished DOX-induced alterations in these parameters. Moreover, DOX significantly decreased the expression level of AMP-activated protein kinase (AMPK). Meanwhile, DOX induced activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt/PKB) and mammalian target of rapamycin (mTOR) pathways that cross talked with AMPK. On the contrary, IRB successfully counterbalanced all these effects. Collectively, these outcomes suggest that the modulation of AMPK, PI3K, Akt, and mTOR pathways plays a critical role in conferring the protective effects of IRB against DOX nephrotoxicity.

Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues.

Growing evidence supports the pivotal role played by oxidative stress in tissue injury development, thus resulting in several pathologies including cardiovascular, renal, neuropsychiatric, and neurodegenerative disorders, all characterized by an altered oxidative status. Reactive oxygen and nitrogen species and lipid peroxidation-derived reactive aldehydes including acrolein, malondialdehyde, and 4-hydroxy-2-nonenal, among others, are the main responsible for cellular and tissue damages occurring in redox-dependent processes. In this scenario, a link between the endocannabinoid system (ECS) and redox homeostasis impairment appears to be crucial. Anandamide and 2-arachidonoylglycerol, the best characterized endocannabinoids, are able to modulate the activity of several antioxidant enzymes through targeting the cannabinoid receptors type 1 and 2 as well as additional receptors such as the transient receptor potential vanilloid 1, the peroxisome proliferator-activated receptor alpha, and the orphan G protein-coupled receptors 18 and 55. Moreover, the endocannabinoids lipid analogues N-acylethanolamines showed to protect cell damage and death from reactive aldehydes-induced oxidative stress by restoring the intracellular oxidants-antioxidants balance. In this review, we will provide a better understanding of the main mechanisms triggered by the cross-talk between the oxidative stress and the ECS, focusing also on the enzymatic and non-enzymatic antioxidants as scavengers of reactive aldehydes and their toxic bioactive adducts.