Oxidative Stress-related Effects Research Articles

A comprehensive study of oxidative stress-related effects on the prognosis and drug therapy of cervical cancer.

Cervical cancer (CC) is a serious global disease with poor prognoses and a significant recurrence rate in patients with advanced disease. Oxidative stress (OS) greatly influences many types of human cancers, making it crucial to understand the functional mechanisms of OS-related genes in CC. The transcriptome and clinical data of three normal samples and 306 patients with CC were obtained from The Cancer Genome Atlas dataset. The GSE44001 dataset was acquired from the Gene Expression Omnibus database. OS-related subtypes in the cohort with CC were identified using unsupervised hierarchical clustering, univariate Cox analysis, gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator regression analysis. Additionally, molecular pathways that differ across subtypes were determined and OS-related genes linked to the prognosis of patients of CC were determined. Finally, a clinical prognostic gene signature was developed and validated. The relative infiltration level of immune cell subpopulations in different risk groups and subtypes was evaluated using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERPORT) algorithm and single-sample GSEA (ssGSEA) techniques. The present study established two distinct OS subtypes (OS clusters A and B). Analysis using ssGSEA and CIBERSPORT revealed that OS cluster B exhibited a significant level of immune infiltration. A clinical prognostic gene signature was established using OS-related characteristic genes identified by examining the differentially expressed genes across both subtypes. Furthermore, patients with CC were grouped into high- and low-risk groups, with the low-risk group showing higher survival rates. Additionally, these individuals exhibited significant advantages in terms of survival and immunotherapy. Receiver operating characteristic curve analysis demonstrated the higher predictive value of the clinical prognostic gene signature. The outcomes of the validation group depicted congruence with those recorded in the training group. A new model was constructed based on eight OS-related characteristic genes to aid the prediction of the survival rates of individuals with CC. The present study contributes to the existing literature on the mechanisms of OS genes in CC and offers a fresh perspective for future advancements in immunotherapy for such individuals.

Phenolic Compounds of Rhodiola rosea L. as the Potential Alternative Therapy in the Treatment of Chronic Diseases.

The roots and rhizomes of Rhodiola rosea L. (Crassulaceae), which is widely growing in Northern Europe, North America, and Siberia, have been used since ancient times to alleviate stress, fatigue, and mental and physical disorders. Phenolic compounds: phenylpropanoids rosavin, rosarin, and rosin, tyrosol glucoside salidroside, and tyrosol, are responsible for the biological action of R. rosea, exerting antioxidant, immunomodulatory, anti-aging, anti-fatigue activities. R. rosea extract formulations are used as alternative remedies to enhance mental and cognitive functions and protect the central nervous system and heart during stress. Recent studies indicate that R. rosea may be used to treat diabetes, cancer, and a variety of cardiovascular and neurological disorders such as Alzheimer's and Parkinson's diseases. This paper reviews the beneficial effects of the extract of R. rosea, its key active components, and their possible use in the treatment of chronic diseases. R. rosea represents an excellent natural remedy to address situations involving decreased performance, such as fatigue and a sense of weakness, particularly in the context of chronic diseases. Given the significance of mitochondria in cellular energy metabolism and their vulnerability to reactive oxygen species, future research should prioritize investigating the potential effects of R. rosea main bioactive phenolic compounds on mitochondria, thus targeting cellular energy supply and countering oxidative stress-related effects.

A comprehensive characterization and therapeutic properties in ripened Noni fruits (Morinda citrifolia L.)

In this study, methanolic extracts from fresh ripening noni fruits (NFs) (Morinda citrifolia) were analyzed using GC-MS, FTIR, and XRD methods. Comprehensive assessments were studied by proximate analysis (PA), higher heat value (HHV), bulk density (BD) and swelling index (SI). The qualitative analysis of the ripening NFs extracts in various solvents, including distilled water, chloroform, dimethyl sulfoxide (DMSO), dimethyl formamide, and methanol, revealed positive results for starch, terpenoids, saponin, and cardiac glycosides. The percentages of volatile matter, ash content and fixed carbon in PA are 78.799±0.592, 7.18±0.044 and 14.02±0.553, respectively. To use biomass as energy, PA is essential that burns in a gaseous state (volatile matter), solid-state (fixed carbon), and inorganic waste material (ash). It is important to consider the HHV of 17.185±0.103 MJ/kg when estimating the potential for energy recovery from the fruit's biomass. Compositional analysis (CA) was used to determine the percentages of the extractive contents (4.497±0.346), cellulose (33.114±0.261), lignin (9.569±0.399), and hemicellulose (17.89±0.608), all of which have substantial antibacterial properties. Our research looked at its BD (0.312±0.001g/cm3) and SI (1.535±0.022%), resulting in increased susceptibility of the biomass to microbial activity. FTIR and XRD reveal C-O, O-H, N-H, O=C=O, C-H, and O-H linkages with solid lattice spacing. It helps to determine how a substance will interact with biological tissue following implantation. However, no research documents were found in any literature about the oil from noni fruits for the purpose of external pain relief. Advice on using NFs oil for pain treatment comes from our field study of a woman who is 80 years old. In ripening NFs extract, GC-MS analysis identified 100 phytochemicals, including D-limonene, 3-carene, gamma-terpinene, methyl eugenol, caryophyllene, hentriacontane etc. GCMS and virtual screening-cum-molecular docking studies have been done and reported first time to check the documentation and look for caryophyllene that could be used for pain-relieving properties. These compounds have been shown to have antioxidant, antimicrobial, anticancer, inflammation in the brain and oxidative stress-related effects. Our research confirms the bioactive potential of ripening NFs as an alternative medication source.

Metabolomics analysis of antiquitin deficiency in cultured human cells and plasma: Relevance to pyridoxine-dependent epilepsy.

Deficiency of antiquitin (α-aminoadipic semialdehyde dehydrogenase), an enzyme involved in lysine degradation and encoded by ALDH7A1, is the major cause of vitamin B6 -dependent epilepsy (PDE-ALDH7A1). Despite seizure control with high dose pyridoxine (PN), developmental delay still occurs in approximately 70% of patients. We aimed to investigate metabolic perturbations due to possible previously unidentified roles of antiquitin, which may contribute to developmental delay, as well as metabolic effects of high dose pyridoxine supplementation reflecting the high doses used for seizure control in patients with PDE-ALDH7A1. Untargeted metabolomics by high resolution mass spectrometry (HRMS) was used to analyze plasma of patients with PDE-ALDH7A1 and two independently generated lines of cultured ReNcell CX human neuronal progenitor cells (NPCs) with CRISPR/Cas mediated antiquitin deficiency. Accumulation of lysine pathway metabolites in antiquitin-deficient NPCs and western-blot analysis confirmed knockdown of ALDH7A1. Metabolomics analysis of antiquitin-deficient NPCs in conditions of lysine restriction and PN supplementation identified changes in metabolites related to the transmethylation and transsulfuration pathways and osmolytes, indicating a possible unrecognized role of antiquitin outside the lysine degradation pathway. Analysis of plasma samples of PN treated patients with PDE-ALDH7A1 and antiquitin-deficient NPCs cultured in conditions comparable to the patient plasma samples demonstrated perturbation of metabolites of the gamma-glutamyl cycle, suggesting potential oxidative stress-related effects in PN-treated patients with PDE-ALDH7A1. We postulate that a model of human NPCs with CRISPR/Cas mediated antiquitin deficiency is well suited to characterize previously unreported roles of antiquitin, relevant to this most prevalent form of pyridoxine-dependent epilepsy.

Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line

Lysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very little is known about the general toxicity of these compounds, especially about their possible neurotoxic effects at the cell level. The aim of this study was to address these gaps by assessing the toxic effects of 24-hour exposure to LSD and PCP in the concentration range of 0.39–100 μmol/L in the human neuroblastoma SH-SY5Y cell line. After cell viability was established, cells treated with concentrations that reduced their viability up to 30 % were further subjected to the alkaline comet assay and biochemical assays that enable estimation of oxidative stress-related effects. Treatment with LSD at 6.25 μmol/L and with PCP at 3.13 μmol/L resulted with 88.06±2.05 and 84.17±3.19 % of viable cells, respectively, and led to a significant increase in primary DNA damage compared to negative control. LSD also caused a significant increase in malondialdehyde level, reactive oxygen species (ROS) production, and glutathione (GSH) level, PCP significantly increased ROS but lowered GSH compared to control. Treatment with LSD significantly increased the activities of all antioxidant enzymes, while PCP treatment significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) but decreased catalase (CAT) activity compared to control. Our findings suggest that LSD has a greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.

Foliar spraying of biogenic CuO nanoparticles protects the defence system and photosynthetic pigments of lettuce (Lactuca sativa)

Engineered nanoparticles (NPs) can act as biostimulants (fertilizers) or cause toxicity in plants (phytotoxicity) depending on several factors. When toxicity is produced, it can lead to oxidative stress, disturbing the plant's oxidative defence system. Biogenic NPs, obtained by green synthesis, are an interesting alternative which obviates toxicity and oxidative stress-related effects. The object of this study was to evaluate how biogenic CuO NPs synthesized with green tea (20 mg per plant) influence the defence system and the photosynthetic pigment content of Lactuca sativa in pot experiments under greenhouse conditions. Moreover, the exposure routes (foliar spraying and soil irrigation) and the forms of Cu applied (nanoscale and ionic) were compared. The defence system of L. sativa was accessed by antioxidant enzymatic activity [ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD)]; secondary metabolites or antioxidant non-enzymatic activity (total flavonoids and phenolic compounds); photosynthetic pigments [chlorophyll a and b and carotenoids]; and nitric oxide levels [R-S-nitrosothiols (RSNOs) and nitrite (NO2−)]. Foliar spraying of CuO NPs reduced APX, but there were no variations in CAT, POD, or SOD activities or photosynthetic pigment contents. However, levels of RSNOs and secondary metabolites increased. In contrast, treatments with CuSO4 raised the APX level and reduced levels of RSNOs, chlorophyll b and carotenoids. Soil irrigation with CuO NPs did not increase enzymatic activity, however it reduced the chlorophyll a and b contents. The use of biogenic CuO NPs via foliar spray showed promising results in protecting lettuce from oxidative stress.

Oxidative costs of cooperation in cooperatively breeding Damaraland mole-rats.

Within cooperatively breeding societies, individuals adjust cooperative contributions to maximize indirect fitness and minimize direct fitness costs. Yet, little is known about the physiological costs of cooperation, which may be detrimental to direct fitness. Oxidative stress, the imbalance between reactive oxygen species (by-products of energy production) and antioxidant protection, may represent such a cost when cooperative behaviours are energetically demanding. Oxidative stress can lead to the accumulation of cellular damage, compromising survival and reproduction, thus mediating the trade-off between these competing life-history traits. Here, we experimentally increased energetically demanding cooperative contributions in captive Damaraland mole-rats (Fukomys damarensis). We quantified oxidative stress-related effects of increased cooperation on somatic and germline tissues, and the trade-off between them. Increased cooperative contributions induced oxidative stress in females and males, without increasing somatic damage. Males accumulated oxidative damage in their germline despite an increase in antioxidant defences. Finally, oxidative damage accumulation became biased towards the germline, while antioxidant protection remained biased towards the soma, suggesting that males favour the maintenance of somatic tissues (i.e. survival over reproduction). Our results show that heightened cooperative contributions can ultimately affect direct fitness through oxidative stress costs, which may represent a key selective pressure for the evolution of cooperation.

Oxidative stress-related effects induced by micronized polyethylene terephthalate microparticles in the Manila clam

ABSTRACTMicroplastic (MP) contamination represents a serious threat for marine organisms. Several lab studies demonstrated adverse effects induced by exposure to different MP polymers toward diverse marine species. However, the information regarding toxicity of polyethylene terephthalate (PET) MPs is largely unknown. The present study was aimed at investigating the adverse effects induced by 7-day exposure to two concentrations (0.125 or 12.5 µg/ml) micronized, irregular shaped and variable size PET microparticles (PET-MPs) toward Manila clam (Ruditapes philippinarum). Histological analyses were performed to assess tissue damage on digestive glands, gonads, gut and gills, whereas oxidative stress-related effects, including the concentration of pro-oxidant molecules, activity of antioxidant (superoxide dismutase – SOD, catalase – CAT and glutathione peroxidase – GPx) and detoxifying (glutathione S-transferase – GST) enzymes, as well as levels of lipid peroxidation, were determined in gills and digestive gland. Our results showed that clams ingest and egest micronized PET-MPs, but no marked histological alterations to bivalve tissues occurred. Although PET-MPs did not produce oxidative stress in the digestive gland, these materials significantly altered oxidative status of gills, leading to lipid peroxidation. No apparent clear indication of a weakness of bivalve health status was obtained in this study.

The impact of chronic environmental metal and benzene exposure on human urinary metabolome among Chinese children and the elderly population

The health effects of metals and benzene exposure have been extensively investigated; however, information on the impact of chronic environmental metal and benzene exposure on human urinary metabolome is limited. In this study, a total of 566 participants, including 352 elderly and 214 children, were split into the “exposed” and “control” groups. The urine samples of all the participants were collected and stored at − 80 °C until analysis. The urinary levels of 17 metals and S-phenylmercapturic acid (S-PMA) were determined by the ICP–MS and LC–MS/MS methods to comprehensively assess the personal metal and benzene exposure levels, respectively. Then, the individual levels of metal and benzene exposure were correlated to the metabolic consequences of ambient pollutant exposure, which were previously observed in our metabolomics study. As a result, multiple metals, including Cd, Co, Cr, Cu, Fe, Hg, Li, Mo, Ni, Pb, Se, and Zn, exhibited a significant linear dose–dependent association with one or more urinary metabolites, including two amino acids (pyroglutamic acid and 3-methylhistidine), three organic acids (azelaic acid, decenedioic acid, and hydroxytetradecanedioic acid), ten medium-chainacylcarnitines (heptenedioylcarnitine, octenedioylcarnitine, nonenedioylcarnitine, decenedioylglucuronide, 3-hydroxydecanoylcarnitine, dodecanedioylcarnitine, nonanoylcarnitine, decadienylcarnitine, hydroxydodecenoylcarnitine, dodecadienylcarnitine, and dodecenoylcarnitine), and one glucuronide conjugate (decenedioylglucuronide). These observations indicate that the increased environmental metal exposure has caused various oxidative stress-related effects, including the depletion of antioxidants, accelerated muscle proteolysis, elevated activity of UGTs, increased lipid peroxidation, and the disorder of mitochondrial lipid metabolism among exposed children and the elderly. The current study provides new insights into the biological effects induced by metal exposure in the environment.

The Adverse Effects of Environmental Noise Exposure on Oxidative Stress and Cardiovascular Risk.

Epidemiological studies have provided evidence that traffic noise exposure is linked to cardiovascular diseases such as arterial hypertension, myocardial infarction, and stroke. Noise is a nonspecific stressor that activates the autonomous nervous system and endocrine signaling. According to the noise reaction model introduced by Babisch and colleagues, chronic low levels of noise can cause so-called nonauditory effects, such as disturbances of activity, sleep, and communication, which can trigger a number of emotional responses, including annoyance and subsequent stress. Chronic stress in turn is associated with cardiovascular risk factors, comprising increased blood pressure and dyslipidemia, increased blood viscosity and blood glucose, and activation of blood clotting factors, in animal models and humans. Persistent chronic noise exposure increases the risk of cardiometabolic diseases, including arterial hypertension, coronary artery disease, diabetes mellitus type 2, and stroke. Recently, we demonstrated that aircraft noise exposure during nighttime can induce endothelial dysfunction in healthy subjects and is even more pronounced in coronary artery disease patients. Importantly, impaired endothelial function was ameliorated by acute oral treatment with the antioxidant vitamin C, suggesting that excessive production of reactive oxygen species contributes to this phenomenon. More recently, we introduced a novel animal model of aircraft noise exposure characterizing the underlying molecular mechanisms leading to noise-dependent adverse oxidative stress-related effects on the vasculature. With the present review, we want to provide an overview of epidemiological, translational clinical, and preclinical noise research addressing the nonauditory, adverse effects of noise exposure with focus on oxidative stress. Antioxid. Redox Signal. 28, 873–908.

Cellular and molecular oxidative stress-related effects in uterine myometrial and trophoblast-decidual tissues after perigestational alcohol intake up to early mouse organogenesis.

The placenta plays a major role in embryo-fetal defects and intrauterine growth retardation after maternal alcohol consumption. Our aims were to determine the oxidative status and cellular and molecular oxidative stress effects on uterine myometrium and trophoblast-decidual tissue following perigestational alcohol intake at early organogenesis. CF-1 female mice were administered with 10% alcohol in drinking water for 17days prior to and up to day 10 of gestation. Control females received ethanol-free water. Treated mice had smaller implantation sites compared to controls (p<0.05), diminished maternal vascular lumen, and irregular/discontinuous endothelium of decidual vessels. The trophoblast giant cell layer was disorganized and presented increased abnormal nuclear frequency. The myometrium of treated females had reduced nitrite content, increased superoxide dismutase activity, and reduced glutathione (GSH) content (p<0.05). However, the trophoblast-decidual tissue of treated females had increased nitrite content (p<0.05), increased GSH level (p<0.001), increased thiobarbituric acid-reactive substance concentration (p<0.001), higher 3-nitrotyrosine immunoreaction, and increased apoptotic index (p<0.05) compared to controls. In summary, perigestational alcohol ingestion at organogenesis induced oxidative stress in the myometrium and trophoblast-decidual tissue, mainly affecting cells and macromolecules of trophoblast and decidual tissues around early organogenesis, in CF-1 mouse, and suggests that oxidative-induced abnormal early placental formation probably leads to risk of prematurity and fetal growth impairment at term.

Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure

Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4+ T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4+ T cells in association with increased production of pro-inflammatory cytokines IFN-γ and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE.

Effects of Curcuma longa dietary inclusion against Eimeria spp. in naturally-infected lambs

Ovine coccidiosis caused by Eimeria spp. can negatively impact health and overall productive performance in sheep with mortalities up to 20% in lambs. It is characterized by high production of pro-inflammatory cytokines and oxidative stress that can damage intestinal tissue. Currently, only drugs are used for the treatment of ovine coccidiosis. Nevertheless, anticoccidial resistance and the concern of drug residues in edible tissues and milk have prompted the evaluation of alternatives to prevent and control this disease. Based on preliminary findings, the use of Curcuma longa dietary supplementation was evaluated in this trial. Twenty crossbred lambs naturally infected with Eimeria spp., aged 28-days-old with an average weight of 12kg, were divided in five groups. Three groups were treated orally for 14 days with 50mg/kg, 100mg/kg, or 200mg/kg of C. longa. A placebo-treated group and untreated controls were included in this trial, too. Stool samples were obtained every other day to determine anticoccidial efficacy. Also, animals were weighed on day 0 and 42. To evaluate the immunomodulatory activity of curcumin, a proinflammatory (IFN-γ) and an immunoregulatory (IL-10) cytokine were measured by ELISA. Lipid peroxidation and nitrite generation were determined by means of the serum malondialdehyde test and the Griess reaction, respectively. C. longa anticoccidial activity increased over time in treated groups and reached a 100% efficacy on day 42. Animals treated with 200mg/kg of this plant gained twice the daily weight recorded for untreated groups. IL-10 levels were higher in supplemented animals, whereas lipid peroxidation and generation of nitrites were significantly lower. Results showed that curcumin administration may reduce oocyst output, weight-loss, inflammation and oxidative stress-related effects caused by Eimeria spp. infection in lambs.

Human metabolic responses to chronic environmental polycyclic aromatic hydrocarbon exposure by a metabolomic approach.

The toxicities of polycyclic aromatic hydrocarbons (PAHs) have been extensively explored due to their carcinogenic and mutagenic potency; however, little is known about the metabolic responses to chronic environmental PAH exposure among the general population. In the present study, 566 healthy volunteers were dichotomized into exposed and control groups to investigate PAH-induced perturbations in the metabolic profiles. Nine urine PAH metabolites were measured by a sensitive LC-MS/MS method to comprehensively evaluate the PAH exposure level of each individual, and the metabolic profiles were characterized via a LC-MS-based metabolomic approach. PAH exposure was correlated to its metabolic outcomes by linear and logistic regression analyses. Metabolites related to amino acid, purine, lipid, and glucuronic acid metabolism were significantly changed in the exposed group. 1-Hydroxyphenanthrene and dodecadienylcarnitine have potential as sensitive and reliable biomarkers for PAH exposure and its metabolic outcomes, respectively, in the general population. These findings generally support the hypothesis that environmental PAH exposure causes oxidative stress-related effects in humans. The current study provides new insight into the early molecular events induced by PAH exposure in the actual environment.

An integrative assessment to determine the genotoxic hazard of estuarine sediments: combining cell and whole-organism responses.

The application of the Comet assay in environmental monitoring remains challenging in face of the complexity of environmental stressors, e.g., when dealing with estuarine sediments, that hampers the drawing of cause-effect relationships. Although the in vitro Comet assay may circumvent confounding factors, its application in environmental risk assessment (ERA) still needs validation. As such, the present work aims at integrating genotoxicity and oxidative DNA damage induced by sediment-bound toxicants in HepG2 cells with oxidative stress-related effects observed in three species collected from an impacted estuary. Distinct patterns were observed in cells exposed to crude mixtures of sediment contaminants from the urban/industrial area comparatively to the ones from the rural/riverine area of the estuary, with respect to oxidative DNA damage and oxidative DNA damage. The extracts obtained with the most polar solvent and the crude extracts caused the most significant oxidative DNA damage in HepG2 cells, as measured by the formamidopyrimidine-DNA glycosylase (FPG)-modified Comet assay. This observation suggests that metals and unknown toxicants more hydrophilic than polycyclic aromatic hydrocarbons may be important causative agents, especially in samples from the rural part of the estuary, where oxidative DNA damage was the most significant. Clams, sole, and cuttlefish responded differentially to environmental agents triggering oxidative stress, albeit yielding results accordant with the oxidative DNA damage observed in HepG2 cells. Overall, the integration of in vivo biomarker responses and Comet assay data in HepG2 cells yielded a comparable pattern, indicating that the in vitro FPG-modified Comet assay may be an effective and complementary line-of-evidence in ERA even in particularly challenging, natural, scenarios such as estuarine environments.

Hydroxyl radicals ([rad]OH) are associated with titanium dioxide (TiO2) nanoparticle-induced cytotoxicity and oxidative DNA damage in fish cells

TiO2 nanoparticles (<100nm diameter) have been reported to cause oxidative stress related effects, including inflammation, cytotoxicity and genomic instability, either alone or in the presence of UVA irradiation in mammalian studies. Despite the fact that the aquatic environment is often the ultimate recipient of all contaminants there is a paucity of data pertaining to the potential detrimental effects of nanoparticles on aquatic organisms. Therefore, these investigations aimed to evaluate the potential cytotoxic and genotoxic effects of TiO2 nanoparticles on goldfish skin cells (GFSk-S1), either alone or in combination with UVA. Whilst neutral red retention (NRR) assay (a measure of lysosomal membrane integrity) was used to evaluate cell viability, a modified Comet assay using bacterial lesion-specific repair endonucleases (Endo-III, Fpg) was employed to specifically target oxidative DNA damage. Additionally, electron spin resonance (ESR) studies with different spin traps were carried out for qualitative analysis of free radical generation. For cell viability, TiO2 alone (0.1–1000μgml−1) had little effect whereas co-exposure with UVA (0.5–2.0kJm−2) caused a significant dose-dependent decrease which was dependent on both the concentration of TiO2 and the dose of UVA administered. For the Comet assay, doses of 1, 10 and 100μgml−1 in the absence of UVA caused elevated levels of Fpg-sensitive sites, indicating the oxidation of purine DNA bases (i.e. guanine) by TiO2. UVA irradiation of TiO2-treated cells caused further increases in DNA damage. ESR studies revealed that the observed toxic effects of nanoparticulate TiO2 were most likely due to hydroxyl radical (OH) formation.

Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium

Cadmium (Cd) is a potential pollutant of the environment. It manifests cyto-toxic effects in different organs in animals. In the present study, intraperitoneal injection of CdCl 2 (1 mg/kg body weight) increased lipid peroxidation in Swiss mice testes indicating oxidative stress during 5th to 8th week of post-treatment .The enzymatic activity of superoxide dismutase (SOD), catalase (CT) and peroxidase (PD) were significantly decreased over the post-treatment phase in Cd-treated mice testes compared to vehicle controls. Further, ascorbic acid content also declined significantly in Cd-exposed mice testes. Following Cd treatment, a marked increase in sperm abnormality percentage and significant decrease in sperm count was observed. The purpose of the present study was to evaluate the effect of vitamins C and E supplementation on Cd-treated mice testes. Therefore, Cd-treated mice groups were injected with vitamins C and E, separately, to assess the effect of the vitamins in combating Cd-induced cytotoxicity and other manifestations. Supplementation of vitamin C (10 mg/kg body weight) and vitamin E (100 mg/kg body weight) to Cd-induced mice groups declined lipid peroxidation, increased sperm count profile, depressed the percentage of sperm abnormality, increased the activity of antioxidant enzymes mentioned above and also increased the concentration of ascorbic acid to a measurable extent. The role of vitamins in reducing oxidative stress-related effects on spermatogenesis in Cd-treated Swiss mice testes have been reported.

Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women

Objective The present study was undertaken to evaluate plasma TNFα, IL-1β, IL-10; and urinary hydroxyproline (Hyp) and calcium (Ca) as bone resorption markers in postmenopausal women compared with premenopausal ones; and to assess the effects of HRT upon these cytokines and bone turnover markers. Patients and methods The study involved 50 healthy postmenopausal women, and 25 healthy premenopausal women (control group). Postmenopausal women were randomly divided into two subgroups: women receiving cycle HRT schedule (0.625 mg conjugated estrogen from days 1 to 28 + 5 mg medroxyprogesterone acetate from days 18 to 28) for 2 months ( n = 25); and second subgroup consisted of women receiving continue HRT schedule (0.625 mg conjugated estrogen + 2.5 mg medroxyprogesterone acetate from days 1 to 28) for 2 months ( n = 25). Plasma TNFα, IL-1β and IL-10 concentrations were measured with ELISA kits. Fasting urinary Hyp was measured by Ehrlich's spectrophotometric reaction. Ca was determined by oxalate precipitation and the redox titration procedure. Statistical significance was analysed by Kruskal–Wallis plus post hoc Mann–Whitney U-tests for multiple comparisons, Wilcoxon signed ranks test for paired data, and Pearson correlation test. Results Compared with premenopausal individuals, postmenopausal women have increased plasma TNFα, IL-1β, IL-10 ( p < 0.0001, p < 0.0001, and p < 0.001, respectively); and increased urinary Hyp and Ca concentrations ( p < 0.05). HRT (both cycle and continue schedules) lead to a significant decrease in TNFα, IL-1β and urinary Hyp concentrations, and has no effect uppon IL-10 levels. HRT reverses increased urinary Hyp and Ca excretion to the premenopausal level. There is a significant positive correlation between pre- and post-HRT IL-1β levels in both cycle and continue subgroups ( r = 0.437, p < 0.05; and r = 0.656, p < 0.01, respectively), and between pre-HRT IL-1β and urinary Ca ( r = 0.509, p < 0.01; and r = 0.415, p < 0.05). There is a significant negative correlation between post-HRT IL-10 and TNFα levels in continue HRT receiving group ( r = −0.446, p < 0.05). Urinary Hyp in cycle and continue HRT received subgroups are correlated with post-treatment values ( r = 0.455, p < 0.05; and r = 0.776, p < 0.01). Conclusions Plasma TNFα, IL-1β, IL-10; and urinary Hyp and Ca increase with menopause. We suggest that the increase of IL-10 is secondary to the elevation of TNFα and IL-1β and that the increase of IL-10 is a compensatory mechanism, by which this anti-inflammatory cytokine counteracts to pro-inflammatory TNFα and IL-1β, and thus balances their osteoclast activating and oxidative stress-related effects. Two months duration HRT (cycle and continue schedule) lead to the significant decrease in plasma TNFα, IL-1β and urinary Hyp concentrations. HRT reverses increased Hyp and Ca excretion to the premenopausal level. So, HRT, decreasing Th1 cytokines (TNFα, IL-1β) probably improve the aberation of Th1/Th2 balance that is implicated in various pathological conditions. However, because of the relatively small number of participants and short duration of the therapy, further studies are necessary to establish a risk/benefit ratio for HRT to view effects on cytokine pattern and bone metabolism.

Effects of Manganese on Oxidative Stress in CATH.a Cells

The present study addressed the effects of Mn on oxidative stress in a catecholaminergic CATH.a cell line. Oxidative stress was measured with the fluorescent dye, 2′,7′-dichlorofluoroscein (DCFH). In the diacetate form, the dye is taken up by the cells and cleaved by esterases, effectively trapping it within the intracellular space. DCFH is subsequently oxidized treatment in the presence of reactive oxygen species (ROS) to the fluorescent DCFH. The fluorescence was analyzed on an ACAS 470 Interactive Laser Cytometer. Treatment of CATH.a cells with MnCl 2 (up to 10 mM) from 10 min up to 48 h was not associated with increased intracellular ROS formation. While manganese (Mn) treatment alone did not increase the rate of ROS formation, when short-term (10 min), Mn treatment was followed for the last 5 min with treatment with H 2O 2, Mn (at concentrations>5 mM) significantly increased ( P<0.05) H 2O 2-induced ROS generation. Prolonged (24 h) Mn treatment prior to exposure to H 2O 2 was associated with a statistically significant ( P<0.05) reduction in ROS generation compared with cells treated with H 2O 2 alone. This statistically significant decrease ( P<0.05) in ROS generation was preserved in CATH.a cells that were treated for 48 h with 10 and 100 μM Mn followed by H 2O 2 exposure. Although the trend for diminished ROS generation was also apparent with 500 and 750 μM Mn (48 h), the decrease did not attain statistical significance. Combined these results suggest that Mn can act as both pro- and antioxidant, and that oxidative stress-related effects of Mn are dependent not only on the intracellular concentrations of the metal, but also the exposure duration, secondary oxidative challenges, and the overall oxidant “buffering” capacity of the cells.