Oxidative Stress In Various Organs Research Articles

Involvement of Nrf2 Signaling in Lead-induced Toxicity.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is used as one of the main protective factors against various pathological processes, as it regulates cells resistant to oxidation. Several studies have extensively explored the relationship between environmental exposure to heavy metals, particularly lead (Pb), and the development of various human diseases. These metals have been reported to be able to, directly and indirectly, induce the production of reactive oxygen species (ROS) and cause oxidative stress in various organs. Since Nrf2 signaling is important in maintaining redox status, it has a dual role depending on the specific biological context. On the one hand, Nrf2 provides a protective mechanism against metal-induced toxicity; on the other hand, it can induce metalinduced carcinogenesis upon prolonged exposure and activation. Therefore, the aim of this review was to summarize the latest knowledge on the functional interrelation between toxic metals, such as Pb and Nrf2 signaling.

Oral supplementation with resveratrol improves hormonal profile and increases expression of genes associated with thermogenesis in oophorectomy mice

Menopause causes important bodily and metabolic changes, which favor the increased occurrence of cardiovascular diseases, obesity, diabetes, and osteoporosis. Resveratrol exerts proven effects on body metabolism, improving glucose and lipid homeostasis and reducing inflammation and oxidative stress in various organs and tissues. Accordingly, this study evaluates the effects of resveratrol supplementation on the expression of markers associated with thermogenesis in brown adipose tissue, and on the body, metabolic and hormonal parameters of female mice submitted to bilateral oophorectomy. Eighteen female mice were randomized into three groups: G1: control (CONTROL), G2: oophorectomy (OOF), and G3: oophorectomy + resveratrol (OOF + RSV); the animals were kept under treatment for twelve weeks, being fed a standard diet and treated with resveratrol via gavage. Body, biochemical, hormonal, and histological parameters were measured; in addition to the expression of markers associated with thermogenesis in brown adipose tissue. The results showed that animals supplemented with resveratrol showed reduced body weight and visceral adiposity, in addition to glucose, total cholesterol, and triglyceride levels; decreased serum FSH levels and increased estrogen levels were observed compared to the OOF group and mRNA expression of PRDM16, UCP1, and SIRT3 in brown adipose tissue. The findings of this study suggest the important role of resveratrol in terms of improving body, metabolic, and hormonal parameters, as well as modulating markers associated with thermogenesis in brown adipose tissue of female mice submitted to oophorectomy.

Didymin protects against polystyrene nanoplastic-induced hepatic damage in male albino rats by modulation of Nrf-2/Keap-1 pathway.

Polystyrene nanoplastics (PS-NPs) are ubiquitous environmental pollutants that can cause oxidative stress in various organs, including the liver. Didymin is a dietary flavanone that displays multiple pharmacological activities. Therefore, the present study evaluated the palliative role of didymin against PS-NPs-induced hepatic damage in rats. Albino rats (n=48) were randomly distributed into 4 groups: control, PS-NPs treated group, PS-NPs + didymin co-administered group, and didymin supplemented group. After 30 days, PS-NPs intoxication lowered the expression of Nrf-2 and anti-oxidant genes [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione-S-transferase (GST), and heme oxygenase-1 (HO-1)], whereas the expression of KEAP1 kelch like ECH associated protein 1 (Keap-1) was increased. PS-NPs exposure also reduced the activities of anti-oxidants enzymes (CAT, SOD, GPx, GSR, GST, GSH, and OH-1), while malondialdehyde (MDA) and reactive oxygen species (ROS) levels were increased. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were increased in PS-NPs-exposed rats. Moreover, inflammatory indices [interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2)] were increased in PS-NPs-exposed rats. Furthermore, PS-NPs intoxication increased the expressions of apoptotic markers including Bax and Caspase-3, as well as reducing Bcl-2 expression. The histopathological analysis showed significant damage in PS-NPs-treated rats. However, didymin supplementation ameliorated all the PS-NPs-induced damage in the liver of rats. Therefore, it was concluded that didymin can act as a remedy against PS-NPs-induced liver toxicity due to its anti-apoptotic, anti-oxidant, and anti-inflammatory activities.

Melatonin exhibits partial protective effects against gemcitabine- and cisplatin-induced kidney and reproductive injuries in mice.

Cisplatin has the potential to cause kidney and reproductive organ injuries, prompting the search for protective agents against cisplatin-induced toxicity. Melatonin, an antioxidant hormone, has shown promise in mitigating oxidative stress in various organs. However, its protective effects on cisplatin-induced kidney and reproductive injuries have not been extensively investigated. The aim of this study was to explore the potential protective effects of melatonin on cisplatin-induced kidney and reproductive injuries when administered in combination with gemcitabine in mice. Male C57BL/6 mice were subjected to a seven-week treatment with gemcitabine plus cisplatin, with or without melatonin intervention. The testis, epididymis, and kidney were assessed through histological analysis and measurement of blood parameters. Treatment with cisplatin led to a significant reduction in testicular weight, histological abnormalities, and alterations in reproductive hormone levels. Melatonin exhibited a slight protective effect on the testis, with higher doses of melatonin yielding better outcomes. However, melatonin did not reverse the effects of cisplatin on the epididymis. Administration of melatonin before and during treatment with cisplatin plus gemcitabine in mice demonstrated a modest protective effect on testicular injuries, while showing limited effects on epididymal injuries. Serum creatinine levels in the group treated with gemcitabine plus cisplatin treatment and high-dose melatonin approached those of the control group, indicating a protective effect on the kidney. These findings underscore the potential of melatonin as a protective agent against cisplatin-induced kidney and reproductive injuries and emphasize the need for further research to optimize its dosage and evaluate its long-term effects.

Acute exposure to fluoxetine leads to oxidative stress and hematological disorder in Danio rerio adults

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is consistently introduced into the environment due to its ongoing consumption and inadequate removal by wastewater treatment plants. As a result, the scientific community has displayed a keen interest in investigating the potential toxicological effects associated with this medication. Nevertheless, there is a scarcity of available data regarding the impact of FLX on blood parameters. With this in mind, this study aimed to evaluate the potential toxicological consequences of FLX at environmentally significant concentrations (5, 16, and 40 ng/L) following a 96-hour acute exposure blood parameters in Danio rerio fish. Moreover, the investigation encompassed an assessment of oxidative stress parameters to determine whether the drug could induce disruptions in the REDOX status of the fish. The findings unveiled that FLX prompted the induction of oxidative stress in various organs of the fish, encompassing the liver, gut, brain, and gills. Notably, the gills and brain exhibited heightened susceptibility to the drug's effects compared to other organs. Furthermore, following acute exposure to FLX, there was an upregulation of antioxidant-related genes (sod, cat, gpx, nrf1, and nrf2), thereby providing additional evidence supporting the induction of oxidative stress in the organs of the fish. Lastly, FLX significantly impacted the customary values of various blood parameters, including glucose, blood urea nitrogen, alanine aminotransferase, alkaline phosphatase, red blood cell count, hemoglobin, and hematocrit. Thus, it can be inferred that FLX harmed the overall health status of the fish, resulting in the development of liver disease, anemia, and other associated illnesses.

Crassostrea gigas peptide PEP-1 prevents tert-butyl hydroperoxide (t-BHP) induced oxidative stress in HepG2 cells.

Exposure to tert-butyl hydroperoxide (t-BHP) leads to cytotoxicity and oxidative stress in various organs and cell types. The bioactive peptides extracted from Oysters exhibit marked antioxidant activity. The impacts of Crassostrea gigas peptides on t-BHP-triggered oxidative stress remain largely unknown. The protective and antioxidant activity of a C.gigas peptide, PEP-1, on t-BHP-treated HepG2 cells, was investigated. PEP-1, this peptide is arginine kinase in oysters. This enzyme functions as a catalyst for the chemical reaction and serves as a phosphate transferase. Since it was the most expressed protein in the adductor muscle of oysters. Our determination showed the lowest level of a toxic concentration of t-BHP (200µM) and the resting concentration of PEP-1 (0-1000ng/ml). PEP-1 exerted a protective effect against t-BHP-induced apoptosis by modifying the expression of pro-and anti-apoptotic proteins. PEP-1 administration reduced nitric oxide and ROS levels while restoring levels of antioxidant proteins in t-BHP-induced cells. PEP-1 exhibited the capacity to enhance the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Therefore, the C. gigas peptide PEP-1 has demonstrated its ability to protect HepG2 cells against oxidative stress induced by t-BHP.

Coenzyme Q10 ameliorates carbofuran induced hepatotoxicity and nephrotoxicity in wister rats

Carbofuran is a widely used poisonous pesticide around the world that helps to control insects during farming. Upon oral ingestion to humans, it exaggerates oxidative stress in various organs like the liver, brain, kidney, and heart. Several studies reported that oxidative stress in the liver initiates and propagates hepatic cell necrosis, ultimately resulting in hepatotoxicity. It also reported that coenzyme Q10 (CoQ10) can neutralize oxidative stress due to its antioxidant properties. However, the hepatoprotective and nephroprotective role of CoQ10 against carbofuran toxicity has not been investigated. Therefore, the present study aimed to evaluate the hepatoprotective and nephroprotective role of CoQ10 in carbofuran-induced hepatotoxicity and nephrotoxicity in a mouse model for the first time. We determined the blood serum diagnostic markers, oxidative stress parameters, antioxidant system, and histopathological characteristics of liver and kidney tissues. The administration of 100 mg/kg of CoQ10 in carbofuran-treated rats significantly attenuated AST, ALT, ALP, serum creatinine, and BUN levels. Moreover, CoQ10 (100 mg/kg) remarkably altered the level of NO, MDA, AOPP, GSH, SOD, and CAT in both the liver and kidney. The histopathological data also unveiled that CoQ10 treatment prevented inflammatory cell infiltration in carbofuran-exposed rats. Therefore, our findings infer that CoQ10 may effectively protect liver and kidney tissues against carbofuran-induced oxidative hepatotoxicity and nephrotoxicity.

The Effect of Fasting on Oxidative Stress in the Vital Organs of New Zealand White Rabbit.

Oxidative stress is defined as the condition in which balance between the synthesis and detoxification of reactive oxygen species in cells is disrupted. This research explored the effects of intermittent and prolonged fasting on malondialdehyde (MDA), carbonyl, reduced glutathione (GSH), and specific activity of catalase as biomarkers for oxidative stress in hearts, brains, and kidneys of New Zealand White (NZW) rabbits. Fifteen NZW rabbits were divided into control, intermittent fasting (IF), and prolonged fasting (PF) groups. The controls were fed ad lib. IF and PF groups were fasted for 16 and 40 hours, respectively, followed by eight hours of non-fasting, for six days and were sacrificed on the 7th day. One hundred mg of heart, brain, and kidney tissues were homogenized in 1 ml of phosphate-buffered saline. MDA, carbonyl, GSH, and catalase were analyzed by spectrophotometry. Data were analyzed using One-way ANOVA and post hoc test. In heart, MDA was significantly greater in the control than in the IF and PF groups. In brain, GSH was greater in the IF than in the PF and control groups. Also, in brain, catalase specific activity was significantly greater in the control than in the IF and PF groups. In kidney, catalase specific activity was significantly less in the PF than in the control group. The effect of fasting on oxidative stress in various organs showed various responses, however fasting reduced oxidative stress based on MDA and GSH levels in the heart and brain, respectively.

EFEK KATEKIN DAUN GAMBIR (UNCARIA GAMBIR ROXB) TERHADAP KADAR MALONDIALDEHID SERUM DAN EKSPRESI GEN SIRTUIN 1 PADA HIPOKAMPUS MENCIT BETINA MODEL PENUAAN

Aging is a physiological process characterized by progressive loss of physiological integrity that leads to impaired function and increased susceptibility to death. Oxidative stress is one of the factors that cause aging due to an imbalance between the amount of oxidants and antioxidants. In oxidative stress condition, malondialdehyde levels increase. D-galactose can induce aging in various organ systems. D-galactose induces oxidative stress in various organs through increased production of reactive oxygen species (ROS) and advanced glycation endproducts. In oxidative stress condition, sirtuin1 (Sirt1) produces ribose O-acetyl-ADP which, later, is reduced into ribose ADP. Both of them have a protective effect against oxidative stress. Consumption of antioxidants may prevent aging. Gambir contains health-promoting ingredients such as catechins. This study aims to determine the effect of gambier leaves catechin extract on serum malondialdehyde levels and the expression of sirtuin 1 gene in female mice aging model induced by d-galactose. This is an in vivo experiment with post test-only control group study. The samples were 28 female mice which were divided into 4 groups namely P0, P1, P2, and P3. Each group was injected 150 mg/kgBW d-galactose intraperitoneally. P1, P2, and P3 were treated orally with 100, 200, and 400 mg/kgBW gambir leaves catechin extract, respectively. Statistical test use descriftive analisys. There were significant differences in serum MDA levels in all groups (p=0.002) and there were significant differences between the P0 and P2 groups (p=0.010) and between the P0 and P3 groups (p=0.010). Sirtuin1 gene relative expressions decresead in P1 (0,49), P2 (0,74), and P3 (0,43) as compared to P0 (1.00). Conclusion. Gambir leaves catechin extract reduces serum malondialdehyde levels in aging mouse models induced by d-galactose with an optimal dose of 200mg/kgBW. and cannot reduce the relative expression of Sirt1

Protective Effects of Hydrogen against Irradiation.

Radiation-induced lung injury is characterized by an acute pneumonia phase followed by a fibrotic phase. At the time of irradiation, a rapid, short-lived burst of reactive oxygen species (ROS) such as hydroxyl radicals (•OH) occurs, but chronic radiation-induced lung injury may occur due to excess ROS such as H2O2, O2•-, ONOO-, and •OH. Molecular hydrogen (H2) is an efficient antioxidant that quickly diffuses cell membranes, reduces ROS such as •OH and ONOO-, and suppresses damage caused by oxidative stress in various organs. In 2011, through the evaluation of electron-spin resonance and fluorescent indicator signals, we had reported that H2 can eliminate •OH and can protect against oxidative stress-related apoptotic damage induced by irradiation of cultured lung epithelial cells. We had explored for the first time the radioprotective effects of H2 treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H2-enriched water (for chronic). Thus, we had proposed that H2 be considered a potential radioprotective agent. Recent publications have shown that H2 directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H2 functions as an anti-inflammatory and anti-apoptotic molecule and promotes energy metabolism. The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H2 treatment and its radioprotective effect clinically. This review focuses on major scientific advances in the treatment of H2 as a new class of radioprotective agents.

Aggravation of autism-like behavior in BTBR T+tf/J mice by environmental pollutant, di-(2-ethylhexyl) phthalate: Role of nuclear factor erythroid 2-related factor 2 and oxidative enzymes in innate immune cells and cerebellum

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which manifests itself in early childhood and is distinguished by recurring behavioral patterns, and dysfunction in social/communication skills. Ubiquitous environmental pollutant, di-2-ethylhexyl phthalate (DEHP) is one of the most frequently used plasticizers in various industrial products, e.g. vinyl flooring, plastic toys, and medical appliances. DEHP gets easily released into the environment and leads to human exposure through various routes. DEHP has been described to be linked with oxidative stress in various organs in animal/human studies. Increased concentration of DEHP has also been detected in ASD children which indicates an association between phthalates exposure and ASD. However, effect of DEHP on autism-like behavior has not been investigated previously. Therefore, this study probed the effect of DEHP on autism-like behavior (marble burying, self-grooming and sociability) and innate immune cells (dendritic cells/neutrophils)/cerebellar oxidant-antioxidant balance (NFkB, iNOS, NADPH oxidase, nitrotyrosine, lipid peroxides, Nrf2, SOD, GPx) in BTBR and C57 mice. Our data show that DEHP treatment causes worsening of autism-like behavior in BTBR mice which is associated with enhancement of oxidative stress in innate immune cells and cerebellum with concomitant lack of antioxidant protection. DEHP also causes oxidative stress in C57 mice in both innate immune cells and cerebellar compartment, however there is Nrf2-mediated induction of enzymatic antioxidants which protects them from upregulated oxidative stress. This proposes the notion that ubiquitous environmental pollutants such as DEHP may be involved in the pathogenesis/progression of ASD through dysregulation of antioxidant-antioxidant balance in innate immune cells and cerebellum.

Melatonin Ameliorates BPA Induced Oxidative Stress in Human Red Blood Cells: An In vitro Study.

Bisphenol A (BPA) is a xenobiotic that causes oxidative stress in various organs in living organisms. Blood cells are also an endpoint where BPA is known to cause oxidative stress. Blood cells, especially red blood cells (RBCs), are crucial for maintaining homeostasis and overall wellbeing of the organism. They are highly susceptible to oxidative stress induced by xenobiotics. However, there is limited data about the oxidative stress induced by BPA in blood, especially in red blood cells. This study was carried out to evaluate BPA induced oxidative stress in human RBCs in vitro and its amelioration by melatonin. To find if melatonin exerts a protective effect on the oxidative stress induced by the BPA in human red blood cells in vitro. The erythrocyte suspensions (2 ml) were divided into six groups and treated with 0, 50, 100, 150, 200, and 250 μg/ml of BPA. Another set of erythrocyte suspension with similar BPA treatment and 50 μM Melatonin per group was also set. Incubations lasted for 12 hrs in the dark. Lipid peroxidation, glutathione, glutathione reductase, catalase, and superoxide dismutase were measured as indicators of oxidative stress. BPA caused a significant increase in lipid peroxidation. A decrease in GSH levels was also observed. The activities of all the studied antioxidants also decreased with BPA treatment. Melatonin was seen to mitigate the oxidative stress induced by BPA. Treatment of red blood cells with BPA caused an increase in oxidative stress, while melatonin decreased the induced oxidative stress.

The supplementations with 2-hydroxyoleic acid and n-3 polyunsaturated fatty acids revert oxidative stress in various organs of diet-induced obese mice

Obesity and its related diseases have been associated with oxidative stress. Thus, the search for nutritional strategies to ameliorate oxidative stress in obese individuals seems important. We hypothesized that the supplementation with monounsaturated (2-hydroxyoleic acid (2-OHOA)) and with combined n-3 polyunsaturated (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) fatty acids would ameliorate oxidative stress in different organs, including brain, liver, lungs, and kidneys of adult diet-induced obese (DIO) mice. Adult female ICR-CD1 mice were fed a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of DIO mice received the same HFD, supplemented with 1500 mg of 2-OHOA per kg of HFD and another group with 1500 mg of EPA and 1500 mg of DHA per kg of HFD. At the end of the experiment, several parameters of oxidative stress were assessed. The supplementation with 2-OHOA or with EPA and DHA in DIO mice was able to revert oxidative stress, enhancing the activities of catalase and glutathione reductase, as well as diminishing the activity of xanthine oxidase, the concentration of thiobarbituric acid reactive substances (TBARS) and the ratio between oxidized glutathione and reduced glutathione in several organs. These reached similar values to those of control mice, which were fed a standard diet. These data suggest that supplementation with 2-OHOA and with EPA and DHA could be an effective nutritional intervention to restore an appropriate redox state in DIO mice.

Impact of Pulmonary Exposure to Cerium Oxide Nanoparticles on Experimental Acute Kidney Injury.

Cerium oxide nanoparticles (CeO₂ NPs) are released from diesel engines that use cerium compounds as a catalytic agent to decrease the diesel exhaust particles, leading to human exposure by inhalation to CeO₂ NPs. We have recently demonstrated that pulmonary exposure to CeO₂ NPs induces lung inflammation, thrombosis, and oxidative stress in various organs including kidneys. It is well known that particulate air pollution effects are greater in patients with renal diseases. The aim of this study is to investigate the effects of pulmonary exposure to CeO₂ NPs in a rat model of acute kidney injury (AKI). AKI was induced in rats by a single intraperitoneal injection of cisplatin (CP, 6 mg/kg). Six days later, the rats were intratracheally (i.t.) instilled with either CeO₂ NPs (1 mg/kg) or saline (control), and various renal and pulmonary endpoints were assessed 24 h afterward using histological, colorimetric assay, enzyme-linked immunosorbent assay and Comet assay techniques. CP alone decreased body weight, and increased water intake, urine volume and relative kidney weight. CP also increased the plasma concentrations urea and creatinine, and decreased creatinine clearance. In the kidneys, CP significantly increased renal injury molecule-1, interleukin-6 (IL-6), tumor necrosis factor α (TNFα) and glutathione concentrations, and caused renal tubular necrosis, and DNA injury assessed by Comet assay. All these actions were significantly aggravated in rats given both CP and CeO₂ NPs. Histopathological changes in lungs of CeO₂ NPs-treated rats included marked interstitial cell infiltration and congestion. These were aggravated by the combination of CP + CeO₂ NPs. Moreover, this combination exacerbated the increase in the concentrations of TNFα and IL-6, and the decrease in the activity of pulmonary catalase and total nitric oxide concentration, and lung DNA damage. We conclude that the presence of CeO₂ NPs in the lung exacerbated the renal and lung effects of CP-induced AKI.

Protective Effect of Casperome®, an Orally Bioavailable Frankincense Extract, on Lipopolysaccharide- Induced Systemic Inflammation in Mice.

Introduction: Despite recent advances in critical care, sepsis remains a crucial cause of morbidity and mortality in intensive care units. Therefore, the identification of new therapeutic strategies is of great importance. Since ancient times, frankincense is used in traditional medicine for the treatment of chronic inflammatory disorders such as rheumatoid arthritis. Thus, the present study intends to evaluate if Casperome® (Casp), an orally bioavailable soy lecithin-based formulation of standardized frankincense extract, is able to ameliorate systemic effects and organ damages induced by severe systemic inflammation using a murine model of sepsis, i.e., intraperitoneal administration of lipopolysaccharides (LPS).Methods: Male 60-day-old mice were assigned to six treatment groups: (1) control, (2) LPS, (3) soy lecithin (blank lecithin without frankincense extract), (4) Casp, (5) soy lecithin plus LPS, or (6) Casp plus LPS. Soy lecithin and Casp were given 3 h prior to LPS treatment; 24 h after LPS administration, animals were sacrificed and health status and serum cytokine levels were evaluated. Additionally, parameters representing liver damage or liver function and indicating oxidative stress in different organs were determined. Furthermore, markers for apoptosis and immune cell redistribution were assessed by immunohistochemistry in liver and spleen.Results: LPS treatment caused a decrease in body temperature, blood glucose levels, liver glycogen content, and biotransformation capacity along with an increase in serum cytokine levels and oxidative stress in various organs. Additionally, apoptotic processes were increased in spleen besides a pronounced immune cell infiltration in both liver and spleen. Pretreatment with Casp significantly improved health status, blood glucose values, and body temperature of the animals, while serum levels of pro-inflammatory cytokines and oxidative stress in all organs tested were significantly diminished. Finally, apoptotic processes in spleen, liver glycogen loss, and immune cell infiltration in liver and spleen were distinctly reduced. Casp also appears to induce various cytochromeP450 isoforms, thus causing re-establishment of liver biotransformation capacity in LPS-treated mice.Conclusion: Casp displayed anti-inflammatory, anti-oxidative, and hepatoprotective effects. Thus, orally bioavailable frankincense extracts may serve as a new supportive treatment option in acute systemic inflammation and accompanied liver dysfunction.

Microcystin-LR leads to oxidative damage and alterations in antioxidant defense system in liver and gills of Brycon amazonicus (SPIX & AGASSIZ, 1829)

Microcystin's (MCs) are toxins produced by several groups of cyanobacteria, in water bodies throughout the world, in a process which is being intensified by human action. Among the variants of MCs, MC-LR stands out for its distribution and toxicity. MCs are potent inhibitors of protein phosphatases 1 and 2 A, which causes disruption of the cytoskeleton and consequent cell death. They can also alter the antioxidant system and induce oxidative stress in various organs of many species. There is, however, a lack of information about the effects of MCs on the antioxidant system and oxidative damage in Brazilian fishes. This study evaluated the effect of microcystin-LR on the antioxidant system in liver and gills of the Brazilian fish Brycon amazonicus, after 48 h of i.p injection of 100 μg MC-LR.kg−1 body mass. The liver exhibited increases in the activity of GST (74%) and GPx (217%), and a 47% decrease in SOD activity, with no changes in CAT values. In the gills of fish exposed to MC-LR, CAT and GPx activities did not show significant changes, while SOD and GST activity decreased by 66% and 37%, respectively. The GSH content did not change significantly in the liver, however, a decrease of 43% was observed in the gills. Oxidative damage measured by protein oxidation (PC) and lipoperoxidation (LPO) showed significant effects in both tissues. In hepatic tissue, there was no change in PC levels but LPO increased by 116%. Conversely, in the gills LPO levels did not change but PC increased by 317%. In conclusion, these data show that MC-LR induces oxidative damage in both tissues but in different ways, with being liver most sensitive to LPO and gills to PC. This also suggests that the gills are most sensitive to oxidative stress than liver, due to the inhibition of its antioxidant responses following MC-LR exposure.

Comprehensive comparison of three different animal models for systemic inflammation

BackgroundTo mimic systemic inflammation in humans, different animal models have been developed. Since these models are still discussed controversially, we aimed to comparatively evaluate the most widely used models with respect to the systemic effects, the influence on organ functions and to the underlying pathophysiological processes.MethodsSystemic inflammation was induced in C57BL/6N mice with lipopolysaccharide (LPS) treatment, peritoneal contamination and infection (PCI), or cecal ligation and puncture (CLP). Blood glucose and circulating cytokine levels were evaluated at 0, 2, 4, 6, 12, 24, 48, and 72 h after induction of inflammation. Additionally, oxidative stress in various organs and liver biotransformation capacity were determined. Markers for oxidative stress, apoptosis, infiltrating immune cells, as well as cytokine expression patterns, were assessed in liver and spleen tissue by immunohistochemistry.ResultsTreating mice with LPS and PCI induced a very similar course of inflammation; however, LPS treatment elicited a stronger response. In both models, serum pro-inflammatory cytokine levels rapidly increased whereas blood glucose decreased. Organs showed early signs of oxidative stress, and apoptosis was increased in splenic cells. In addition, liver biotransformation capacity was reduced and there was pronounced immune cell infiltration in both the liver and spleen. Mice exposed to either LPS or PCI recovered after 72 h. In contrast, CLP treatment induced comparatively fewer effects, but a more protracted course of inflammation.ConclusionsThe LPS model of systemic inflammation revealed to be most suitable when being interested in the impact of new therapies for acute inflammation. When using the CLP model to mimic human sepsis more closely, a longer time course should be employed, as the treatment induces delayed development of systemic inflammation.

Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43.

Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6-propyl-2-thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase-3 in PTU-treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose homeostasis via increased oxidative stress in prepubertal mice, thereby affecting germ cell survival and proliferation.

Metabolism Of 4‐Hydroxynonenal In Rat Organs In Response To Ethanol Feeding

4-Hydroxynonenal (HNE) is one of the most abundant lipid peroxidation products and is highly reactive unsaturated aldehyde. The deleterious effects of HNE are ascribed to its post modification of many macromolecules, such as proteins, DNA, and phospholipid. HNE level is not only related to oxidative stress but also depends on the disposal rate via metabolism. Alcohol is known to induce oxidative stress and redox change both of which could potentially influence HNE level. In the present work, we investigated HNE level, redox change, and oxidative stress in various organs including plasma after rats were fed with alcohol for two weeks. Mitochondrial and cytosolic redox was estimated by measuring the ratios of 3-hydroxybutyrate/acetoacetate (BHB/AcAc) and lactate/pyruvate (LAC/PYR), respectively. Alcohol induced redox shift to reductive state in most organs except kidney. Many oxidative stress biomarkers, such as ophthamate and 2-hydroxybutyrate, were significantly increased in all organs including plasma after alcohol feeding. HNE and 4-oxononenal (ONE) were elevated in most organs except brain and plasma. HNE-glutathione (HNE-GSH) conjugate was increased by alcohol in brain and kidney, but slightly decreased in liver and heart compared to control pair-fed. Our data suggested that: (i) alcohol altered redox status in most organs but not in kidney; (ii) redox change is not the only factor causing oxidative stress; (iii) metabolic disposal of HNE is organ dependent. This work is supported by AHA grant (12GRNT12050453) NIH Roadmap Grant R33DK070291.

Hydrogen Sulfide: A Therapeutic Candidate for Fibrotic Disease?

Fibrotic diseases including chronic kidney disease, liver cirrhosis, idiopathic pulmonary fibrosis, and chronic disease account for 45% mortality in the developed countries and pose a great threat to the global health. Many great targets and molecules have been reported to be involved in the initiation and/or progression of fibrosis, among which inflammation and oxidative stress are well-recognized modulation targets. Hydrogen sulfide (H2S) is the third gasotransmitter with potent properties in inhibiting inflammation and oxidative stress in various organs. Recent evidence suggests that plasma H2S level is decreased in various animal models of fibrotic diseases and supplement of exogenous H2S is able to ameliorate fibrosis in the kidney, lung, liver, and heart. This leads us to propose that modulation of H2S production may represent a promising therapeutic venue for the treatment of a variety of fibrotic diseases. Here, we summarize and discuss the current data on the role and underlying mechanisms of H2S in fibrosis diseases related to heart, liver, kidney, and other organs.