Does hypothyroidism augment sun-induced skin damage?

Objectives: We investigated the mutual effects of overt hypothyroidism and prolonged sunlight exposure on free radical accumulation and oxidative skin damage.

Methods: Free radical accumulation was evaluated by monitoring the transformation of 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) into MTT-formazan. The pro-oxidant enzymes xanthine oxidase (XO) and NADPH-diaphorase were measured in the skin. XO activity was estimated based on the yield of uric acid, while NADPH-diaphorase reactivity was monitored histochemically as an indirect marker of nitric oxide synthase and nitric oxide activity. Cellular damage was determined by malondialdehyde formation, a marker for lipid peroxidation.

Results: In the skin of both euthyroid and hypothyroid animals, solar simulated ultraviolet irradiance increased the activity of XO and the NADPHdiaphorase reactivity as a protective response to formation of free radicals, such as reactive oxygen or nitrogen species. These pro-oxidant enzymes diminished in hypothyroid rats. Accumulation of the same amount of free radicals led to similar peroxidation in both hypothyroid and irradiated euthyroid rats. Hypothyroid skin after UV-exposure showed even greater lipid peroxidation.

Discussion: The hypothyroid state could be a risk factor for enhanced oxidative skin damage in chronic photo-exposed skin due to oxidative stress. The lipid peroxidation is one of the major pathways by which photo-oxidative stress promotes photocarcinogenesis and photo-aging.     

Oxidative stress in otosclerosis

Objectives: Otosclerosis is a disease involving abnormal bone turnover in the human otic capsule that results in hearing loss. Several hypotheses have been suggested for the etiopathogenesis of otosclerosis; however, its etiology remains unclear.

Methods: This study evaluated the correlation between otosclerosis and levels of paraoxonase-1 (PON1), arylesterase, total antioxidant status, total oxidant status (TOS), oxidative stress index (OSI), total sulfhydryl (-SH) groups, lipid hydroperoxide, and ceruloplasmin in the serum of otosclerosis patients and healthy subjects with respect to oxidative stress.

Results: In our study, TOS and OSI levels were higher in the otosclerosis patients than in the controls. The PON1 levels showed that oxidative stress was severe, and as a result, antioxidants were consumed and depleted.

Discussion: When an imbalance between oxygen free radical production and antioxidative defense mechanisms occurs, reactive oxygen species levels may increase, which in turn may damage cells and tissues through the peroxidation of phospholipid membrane structures. The body initially responds with increased antioxidant production, but if the oxidative stress is severe, decreased antioxidant levels may result. This study reports expression levels of oxidative stress species in otosclerosis patients.     

Efficacy of antioxidants on incidence of Fusarium root and pod rot diseases in peanut

Several antioxidants namely ascorbic acid, salicylic acid, sodium benzoates, thiouria and catechol were used as seed treatment and foliar spraying to reduce the incidence of root and pod rot diseases of peanut caused by (Fusarium oxysporum, Fusarium solani and Fusarium moniliforme) as well as to determine of phenolic compounds and oxidative enzymes in the treated plants. Each antioxidant was used at different concentrations (2, 4, 6 and 8 mM) against tested pathogenic fungi in vitro. All antioxidants at 8 mM showed the greatest reduction of mycelial growth of the pathogens. In greenhouse experiments, treated seeds (Giza 5 cv.) or foliar spraying of peanut plants after 30 and 60 days from planting date with each antioxidant at 8 mM reduced severity of both diseases. The treated plants with antioxidants increased accumulation of phenolic compounds and activity levels of oxidative enzymes (catalase, peroxidase and polyphenoloxidase) in infected plants compared to healthy plants.

http://zoobank.org/urn:lsid:zoobank.org:pub:AF539C90-4B38-4BFE-B77B-5F2A5D764D7A     

Chlorinative stress in age-related diseases: a literature review

Aging is an agglomerate of biological long-lasting processes that result being inevitable. Main actors in this scenario are both long-term inflammation and oxidative stress. It has been proved that oxidative stress induce alteration in proteins and this fact itself is critically important in the pathophysiological mechanisms leading to diseases typical of aging. Among reactive species, chlorine ones such as hypochlorous acid (HOCl) are cytotoxic oxidants produced by activated neutrophils during chronic inflammation processes. HOCl can also cause damages by reacting with biological molecules. HOCl is generated by myeloperoxidase (MPO) and augmented serum levels of MPO have been described in acute and chronic inflammatory conditions in cardiovascular patients and has been implicated in many inflammatory diseases such as atherosclerosis, neurodegenerative conditions, and some cancers. Due to these data, we decided to conduct an up-to-date review evaluating chlorinative stress effects on every age-related disease linked; potential anti-oxidant countermeasures were also assessed. Results obtained associated HOCl generation to the aging processes and confirmed its connection with diseases like neurodegenerative and cardiovascular pathologies, atherosclerosis and cancer; chlorination was mainly linked to diseases where molecular (protein) alteration constitute the major suspected cause: i.e. inflammation, tissue lesions, DNA damages, apoptosis and oxidative stress itself. According data collected, a healthy lifestyle together with some dietary suggestion and/or the administration of nutracetical antioxidant integrators could balance the effects of chlorinative stress and, in some cases, slow down or prevent the onset of age-releated diseases.     

Phytochemical treatments target kynurenine pathway induced oxidative stress

Objective: The objective of this paper was to link the phytochemical and metabolic research treating quinolinic acid induced oxidative stress in neurodegenerative disorders.

Methods: Quinolinic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, plays a role in the oxidative stress associated with many neurological disorders and is used to simulate disorders such as Parkinson’s disease.

Results: In these models, phytochemicals have been shown to reduce striatal lesion size, reduce inflammation and prevent lipid peroxidation caused by quinolinic acid.

Conclusion: These results suggest that phenolic compounds, a class of phytochemicals, including flavonoids and diarylheptanoids, should be further studied to develop new treatments for oxidative stress related neurological disorders.     

When nature’s robots go rogue: exploring protein homeostasis dysfunction and the implications for understanding human aging disease pathologies

Introduction: Proteins have been historically regarded as ‘nature’s robots’: Molecular machines that are essential to cellular/extracellular physical mechanical properties and catalyze key reactions for cell/system viability. However, these robots are kept in check by other protein-based machinery to preserve proteome integrity and stability. During aging, protein homeostasis is challenged by oxidation, decreased synthesis, and increasingly inefficient mechanisms responsible for repairing or degrading damaged proteins. In addition, disruptions to protein homeostasis are hallmarks of many neurodegenerative diseases and diseases disproportionately affecting the elderly.

Areas covered: Here we summarize age- and disease-related changes to the protein machinery responsible for preserving proteostasis and describe how both aging and disease can each exacerbate damage initiated by the other. We focus on alteration of proteostasis as an etiological or phenomenological factor in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, along with Down syndrome, ophthalmic pathologies, and cancer.

Expert commentary: Understanding the mechanisms of proteostasis and their dysregulation in health and disease will represent an essential breakthrough in the treatment of many (senescence-associated) pathologies. Strides in this field are currently underway and largely attributable to the introduction of high-throughput omics technologies and their combination with novel approaches to explore structural and cross-link biochemistry.     

Hesperetin mitigates acrolein-induced apoptosis in lung cells in vitro and in vivo

Objectives: A number of studies have suggested that acrolein-induced lung injury and pulmonary diseases are associated with the depletion of antioxidants and the production of reactive oxygen species. Therefore, compounds that scavenge reactive oxygen species may exert protective effects against acrolein-induced apoptosis. Because hesperetin, a natural flavonoid, has been reported to have an antioxidant activity, we investigated the effect of hesperitin against acrolein-induced apoptosis of lung cells.

Methods: We evaluated the protective role of hesperetin in acrolein-induced lung injury using Lewis lung carcinoma (LLC) cells and mice.

Results: Upon exposure of LLC cells and mice to acrolein, hesperetin ameliorated the lung inbjury through attenuation of oxidative stress.

Conclusion: In the present report, we demonstrate that hesperetin exhibits a protective effect against acrolein-induced apoptosis of lung cells in both in vitro and in vivo models. Our study provides a useful model to investigate the potential application of hesperetin for the prevention of lung diseases associated with acrolein toxicity.     

Hypochlorous acid as a precursor of free radicals in living systems

Hypochlorous acid (HOCl) is produced in the human body by the family of mammalian heme peroxidases, mainly by myeloperoxidase, which is secreted by neutrophils and monocytes at sites of inflammation. This review discusses the reactions that occur between HOCl and the major classes of biologically important molecules (amino acids, proteins, nucleotides, nucleic acids, carbohydrates, lipids, and inorganic substances) to form free radicals. The generation of such free radical intermediates by HOCl and other reactive halogen species is accompanied by the development of halogenative stress, which causes a number of socially important diseases, such as cardiovascular, neurodegenerative, infectious, and other diseases usually associated with inflammatory response and characterized by the appearance of biomarkers of myeloperoxidase and halogenative stress. Investigations aimed at elucidating the mechanisms regulating the activity of enzyme systems that are responsible for the production of reactive halogen species are a crucial step in opening possibilities for control of the development of the body’s inflammatory response.     

A systems biology-led insight into the role of the proteome in neurodegenerative diseases

Introduction: Multifactorial disorders are the result of nonlinear interactions of several factors; therefore, a reductionist approach does not appear to be appropriate. Proteomics is a global approach that can be efficiently used to investigate pathogenetic mechanisms of neurodegenerative diseases.

Areas covered: Here, we report a general introduction about the systems biology approach and mechanistic insights recently obtained by over-representation analysis of proteomics data of cellular and animal models of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders, as well as of affected human tissues.

Expert commentary: As an inductive method, proteomics is based on unbiased observations that further require validation of generated hypotheses. Pathway databases and over-representation analysis tools allow researchers to assign an expectation value to pathogenetic mechanisms linked to neurodegenerative diseases. The systems biology approach based on omics data may be the key to unravel the complex mechanisms underlying neurodegeneration.     

Parameters of oxidative stress in saliva from patients with aggressive and chronic periodontitis

Objectives: Free radicals play an important role in the onset and progression of many diseases. The aim of this study was to investigate the contribution of oxidative stress in the pathology of aggressive (AgP) and chronic (CP) periodontitis and its relation with the clinical periodontal status.

Methods: Eighty subjects were divided into two groups: 20 patients with AgP and 20 patients with CP with their 20 corresponding matched controls, based on clinical attachment loss (CAL), probing pocket depth (PPD), and bleeding on probing (BOP). Saliva reactive oxygen species (ROS), lipid peroxidation, and non-enzymatic antioxidant defences were measured by luminol-dependent chemiluminescence assay, as thiobarbituric acid-reactive substances (TBARs) and total radical-trapping antioxidant potential (TRAP), respectively. Pearson's correlation and multivariate analysis were used to determine the relationship between ROS and TBARs and the clinical parameters.

Results: ROS and TBARs were increased in AgP while TRAP was decreased, comparing with CP. In AgP, a strong and positive correlation was observed between ROS and TBARs and they were closely associated with CAL and PPD.

Discussion: In AgP, but not in CP, oxidative stress is a high contributor to periodontal pathology and it is closely associated with the clinical periodontal status.     

Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured mammalian cells

Objective: To explore the impact of oxidative insults on mitochondrial dynamics. In mammalian cells, oxidative insults activate stress response pathways including inflammation, cytokine secretion, and apoptosis. Intriguingly, mitochondria are emerging as a sensitive network that may function as an early indicator of subsequent cellular stress responses. Mitochondria form a dynamic network, balancing fusion, mediated by optic atrophy-1 (OPA1), and fission events, mediated by dynamin-related protein-1 (DRP1), to maintain homeostasis.

Methods: Here, we examine the impact of oxidative insults on mitochondrial dynamics in 143B osteosarcoma and H9c2 cardiomyoblast cell lines via confocal microscopy, flow cytometry, and protein-based analyses.

Results: When challenged with hydrogen peroxide (H₂O₂), a ROS donor, both cell lines display fragmentation of the mitochondrial network and loss of fusion-active OPA1 isoforms, indicating that OPA1-mediated mitochondrial fusion is disrupted by oxidative damage in mammalian cells. Consistent with this, cells lacking OMA1, a key protease responsible for cleavage of OPA1, are protected against OPA1 cleavage and mitochondrial fragmentation in response to H₂O₂ challenge.

Discussion: Taken together, these findings indicate that oxidative insults damage OPA1-mediated mitochondrial dynamics in mammalian cells via activation of OMA1, consistent with an emerging role for mitochondrial dynamics as an early indicator of cellular stress signaling.     

Hesperidin attenuates inflammation and oxidative damage in pleural exudates and liver of rat model of pleurisy

Objectives: This study investigated the potential anti-inflammatory effect of hesperidin against carrageenan induced pleurisy in rat model.

Methods: Twenty-four adult female Wistar rats (350 - 450g) were grouped as follows: Group I: rats were administered saline solution only (Normal control group); Group II: rats were administered saline solution (NaCl 0.9%) orally and injected with carrageenan (Inflammation control group); Group III: rats were administered hesperidin only (Hesperidin group); Group IV: rats were administered hesperidin orally and intrapleurally injected with 2% carrageenan (Inflammation treated with hesperidin group). The exudate volume, total leukocyte count, reactive oxygen species (ROS), myeloperoxidase (MPO),δ–aminolevulinate dehydratase (δ-ALA-D), catalase (CAT), superoxide dismutase (SOD), activities as well as non-protein thiol group (NPSH) and thiobarbituric acid reactive substances (TBARS) levels were determined.

Results: Pretreatment with hesperidin at a dose of 80 mg/kg orally per day for 21 days, minimized the increase in pleural exudate volume and leucocyte count and modulated the activities of MPO, SOD and CAT, as well as the levels of ROS, NPSH and TBARS in carrageenan-induced rats.

Conclusion: Our results suggest that hesperidin can elicit its anti-inflammatory action by blocking exudate and leukocyte influx into pleural cavity, inhibiting MPO activity and preventing oxidative damage.     

Hepatitis C virus core or NS3/4A protein expression preconditions hepatocytes against oxidative stress and endoplasmic reticulum stress

Objectives: The occurrence of oxidative stress and endoplasmic reticulum (ER) stress in hepatitis C virus (HCV) infection has been demonstrated and play an important role in liver injury. During viral infection, hepatocytes must handle not only the replication of the virus, but also inflammatory signals generating oxidative stress and damage. Although several mechanisms exist to overcome cellular stress, little attention has been given to the adaptive response of hepatocytes during exposure to multiple noxious triggers.

Methods: In the present study, Huh-7 cells and hepatocytes expressing HCV Core or NS3/4A proteins, both inducers of oxidative and ER stress, were additionally challenged with the superoxide anion generator menadione to mimic external oxidative stress. The production of reactive oxygen species (ROS) as well as the response to oxidative stress and ER stress were investigated.

Results: We demonstrate that hepatocytes diminish oxidative stress through a reduction in ROS production, ER-stress markers (HSPA5 [GRP78], sXBP1) and apoptosis (caspase-3 activity) despite external oxidative stress. Interestingly, the level of the autophagy substrate protein p62 was downregulated together with HCV Core degradation, suggesting that hepatocytes can overcome excess oxidative stress through autophagic degradation of one of the stressors, thereby increasing cell survival.

Duscussion: In conclusion, hepatocytes exposed to direct and indirect oxidative stress inducers are able to cope with cellular stress associated with viral hepatitis and thus promote cell survival.     

A retrospective controlled study of thiol disulfide homeostasis as a novel marker in Crimean Congo hemorrhagic fever

Objectives: Crimean Congo hemorrhagic fever (CCHF) is the second most common hemorrhagic fever worldwide. This study aimed to evaluate the oxidant–antioxidant balance of patients with CCHF by detecting dynamic thiol disulfide homeostasis (TDH), which is a novel oxidative stress marker, and other molecules, including paraoxonase (PON), arylesterase (ARES), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase.

Methods: This retrospective, cross-sectional, controlled study, which involved patients with CCHF and healthy volunteers, measured dynamic TDH using a novel automated method developed by Erel.

Results: We recruited 69 adult patients with CCHF (31 females, 38 males, median age 46 years). The case fatality rate was 1.49% (1/69). Increased disulfide/native thiol and disulfide/total thiol ratios, decreased total antioxidant status (TAS), and increased total oxidant status (TOS) were found in patients with CCHF. TAS, PON, and ARES values were found to be positively correlated with both native and total thiol levels, whereas TOS and CLP were negatively correlated with both, at a significant level. MPO activity was similar in both groups.

Discussion: This is the first study in the literature to evaluate dynamic TDH in CCHF. TDH shifts to the oxidative side in patients with CCHF, leading to an increase in TOS.     

Irreversible oxidative post-translational modifications in heart disease

Introduction: Development of specific biomarkers aiding early diagnosis of heart failure is an ongoing challenge. Biomarkers commonly used in clinical routine usually act as readouts of an already existing acute condition rather than disease initiation. Functional decline of cardiac muscle is greatly aggravated by increased oxidative stress and damage of proteins. Oxidative post-translational modifications occur already at early stages of tissue damage and are thus regarded as potential up-coming disease markers.

Areas covered: Clinical practice regarding commonly used biomarkers for heart disease is briefly summarized. The types of oxidative post-translational modification in cardiac pathologies are discussed with a special focus on available quantitative techniques and characteristics of individual modifications with regard to their stability and analytical accessibility. As irreversible oxidative modifications trigger protein degradation pathways or cause protein aggregation, both influencing biomarker abundance, a chapter is dedicated to their regulation in the heart.     

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress

Background: Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR.

Objective: This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes.

Conclusion: The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.     

Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study

Objectives: Oxidative stress is known to participate in the progression of sepsis. Definite data regarding the behavior of oxidative stress biomarkers in pediatric sepsis is still lacking. This study hypothesized that oxidative stress occurs in pediatric sepsis and that the magnitude of the redox derangement is associated with worse clinical progression.

Methods: Forty-two previously healthy pediatric patients with sepsis and a group of control subjects were included. Oxidative stress and inflammatory activity biomarkers were determined in blood samples. Patients were prospectively followed until their discharge or death.

Results: Patients with non-severe and severe sepsis showed higher levels of plasmatic antioxidant capacity, lower erythrocyte thiol index, lower superoxide dismutase and catalase activities, higher glutathione peroxidase activity, and higher plasmatic F₂-isoprostanes concentration than controls. Patients with severe sepsis had higher NF-kappaB activation than those with non-severe sepsis. Although we observed changes in some biomarkers in patients with worse clinical evolution, the explored biomarkers did not correlate with clinical estimators of outcome.

Discussion: Oxidative stress occurs in pediatric sepsis, resulting in oxidative damage. The explored biomarkers are not useful as outcome predictors in the studied population. The behavior of these biomarkers still needs to be addressed in broader groups of pediatric patients with sepsis.     

Renal mitochondrial oxidative stress is enhanced by the reduction of Sirt3 activity,in Zucker diabetic fatty rats

Objectives: Mitochondrial oxidative stress is involved in the pathogenesis of diabetic kidney disease. The objective of our study is to identify the mechanisms of renal mitochondrial oxidative stress, focusing on Sirt3, which is nicotinamide adenine dinucleotide (NAD⁺; oxidized NAD)-dependent deacetylase in mitochondria.

Methods: Renal mitochondrial oxidative stress and Sirt3 activity, using Zucker diabetic fatty rats (ZDFRs) and cultured proximal tubular cells under high-glucose condition were evaluated.

Results: At 28 weeks of age, ZDFRs exhibited the increased urinary albumin/liver-type fatty acid-binding protein (L-FABP)/8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion, histological tubular cell damage, compared to non-diabetic Zucker Lean rats. In renal mitochondria, acetylated isocitrate dehydrogenase2 (IDH2) and superoxide dismutase2 (SOD2), accompanied with mitochondrial oxidative stress and mitochondrial morphologic alterations, were increased in ZDFRs, indicating inactivation of Sirt3. Additionally, expression of the NAD-degrading enzyme, CD38, was increased, and the NAD⁺/NADH (reduced NAD) ratio was reduced in the renal cortex of ZDFRs. High-glucose stimulation in cultured proximal tubular cells also resulted in an increase in acetylated IDH2/SOD2, CD38 overexpression and a reduction in the NAD⁺/NADH ratio.

Conclusions: Enhancement of mitochondrial oxidative stress in the diabetic kidney was mediated by the reduction of Sirt3 activity. CD38 overexpression may be related to a reduction in the NAD⁺/NADH ratio in the diabetic kidney.     

Circulating microparticles in cardiovascular disease: going on stage!

Context: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. In spite of the fact that treatments are based on risk calculators which in turn are based on population characteristics, it is well known that these methods have definite levels of uncertainty. Recently, more precise diagnostic or predictive methods have been developed based on indicators of vascular and/or cardiac damage in order to supplement this risk evaluation.

Objective: In this review, we describe the main discoveries leading to the idea of using circulating microparticles as a promising and complementary tool in the evaluation of cardiovascular risk.

Methods: A Medline search for the terms cardiovascular diseases, microparticles, miRNAs, diagnosis, prognosis, biomarkers and microvesicles was performed.

Results: We found (i) nine articles, which were relevant to forming the idea of using microparticles as biomarkers in CVDs, and (ii) 15 and 12 experimental clinical studies which describe their potential in primary and secondary CVD prevention, respectively.

Conclusions: The levels of circulating microparticles have been associated with cardiovascular damage in asymptomatic patients as well as in patients who suffered a cardiovascular event, becoming promising diagnostics or prediction biomarkers in recent years.