Oxidative Tissue Damage Research Articles

Cadmium-Induced Perturbation of Spleen Redox Status: Therapeutic Role of Pumpkin Seed Protein Isolate

One of the major threats to humanity is from the exposure of heavy metals irrespective of its source. Cadmium is one of such heavy metals to which humans are exposed in their daily lives via food or environment. Regardless of this, there is no established or efficient way of recycling Cadmium. On the other hand, Pumpkin seeds have innumerable health aiding properties. The present study aims to understand the antioxidative and anti-inflammatory properties of Pumpkin Seeds Protein Isolate (PSPI) against Cadmium mediated oxidative stress in spleen. Twenty male albino rats were divided into four groups; Control, Cadmium treated, Cadmium treated and PSPI 1 supplemented, Cadmium treated and PSPI 2 supplemented. After completion of treatment period (21 days), oxidative stress parameters, ROS generation levels and proinflammatory cytokines were measured along with histopathological evaluations. PSPI supplementation was observed to have significant free radical scavenging activities as evidenced by decreased lipid peroxidation and nitric oxide generation simultaneously with increased glutathione level, activities of superoxide dismutase and catalase. Cadmium also caused an elevation in tumor necrosis factor and interleukin-6 as well as ROS generation levels which were substantially reduced upon supplementation with PSPI. Furthermore, cadmium-induced micro architectural changes in the spleen were also countered upon PSPI supplementation. In summary, both lower and higher doses of PSPI supplementation curtail the cadmium induced oxidative stress, ROS levels, proinflammatory cytokines and damage in the splenic tissue. The Results of this study necessitates further mechanistic study to establish key role of PSPI in amelioration of cadmium toxicity.

Melatonin treatment prevents carbon-tetrachloride induced rat brain injury.

Herein the neuroprotective properties of melatonin, a highly effective antioxidant, administered in a single dose 50mg/kg intraperitoneally, were investigated in the brain tissue of Wistar rats acutely exposed to the toxin carbon-tetrachloride (1mL/kg, intraperitoneally). To assess the degree of whole encephalic mass damage, biochemical parameters related to lipid and protein oxidation, antioxidant enzymes (catalase and superoxide dismutase), glutathione and inducible nitric oxide/arginase pathways were determined. The results showed that carbon-tetrachloride impaired the function of antioxidant enzymes (reduced catalase and superoxide dismutase activities) and reduced glutathione-metabolizing enzymes (reduced glutathione, glutathione S-transferase and peroxidase activity). Furthermore, carbon-tetrachloride increased lipid peroxidation and protein oxidative damage in the brain tissue, as well as myeloperoxidase and inducible nitric oxide synthase content/activities. The application of a single dose of melatonin post intoxication has been able to reverse the disturbance in the function of antioxidant enzymes and alleviate the tissue damage caused by oxidative stress, indicating that melatonin could be a potential therapeutic agent in oxidative-damage related neurodegenerative disorders.

MATERNAL BISPHENOL-A'NIN SIÇAN BÖBREK GELİŞİMİ ÜZERİNDEKİ ETKİSİNİN İNCELENMESİ

Aim: Bisphenol-A (BPA) is an estrogenic chemical used today in the production of epoxy resin and as an additive in other non-polymer plastics. Due to the widespread use of BPA today, human exposure is inevitable. This exposure causes harmful effects on various body systems. The aim of this study is to investigate the effects on the development of the kidneys of the offspring of mother rats exposed to BPA during pregnancy and lactation, as a result of the offspring being exposed to BPA through the placenta and milk. 
 Material and Methods: In this study, 13 adult Wistar albino female rats were divided into 3 groups. In Group 1 (Control group), rats were only administered 1 ml/kg/day corn oil intraperitoneally. Group 2 (25 mg BPA group) rats were administered 25 mg/kg/day BPA; Group 3 (50 mg group) rats were administered 50 mg/kg/day BPA intraperitoneally for 5 weeks. At the end of the experiment, the intracardiac blood and kidney tissues of the offspring rats were taken and examined for urea, total protein, creatinine, TAS, TOS, MDA values. 
 Results: At the end of the study, it was determined that BPA increased serum urea, creatinine and total protein levels, induced the formation of reactive oxygen species causing oxidative damage in kidney tissue, and caused serious structural damages 
 Conclusion: Only mother rats exposed to BPA. BPA transferred to pups via placenta and milk, causing structural damage: narrowing in Bowman's space of renal corpuscle, dilatation in proximal/distal tubules and collecting ducts, occasional cell loss, vacuolization in tubule epithelia.

Carvacrol improved learning and memory and attenuated the brain tissue oxidative damage in aged male rats

Introduction: Aging is an unavoidable process in the body that is accompanied by impaired tissue homeostasis and various changes. Carvacrol has attracted considerable attention for its wide range of pharmacological activities. Therefore, this study attempted to explore the protective effect of carvacrol in aged rats.Materiel and methods: The aged rats were given carvacrol (15 or 30 mg/kg/day) for 4 weeks. Morris water maze and passive avoidance tests were used to determine the learning and memory abilities of the rats. The hippocampus and cortex samples were taken for biochemical analysis.Results: In comparison to young control rats, aged control rats showed learning and memory deficits. There was improvement in the Morris water navigation test and passive avoidance test performance in the treatment groups versus the aged control group. An increment in malondialdehyde (MDA) and a decrease in total thiol groups in the hippocampus and cortex samples of aged control rats in comparison to the young control group were observed. Carvacrol decreased MDA levels and increased total thiol groups in the hippocampus and cortex samples of aged rats.Conclusion: Carvacrol improved learning and memory in aged rats, probably through its anti-oxidation effects.

Enhancement of quality and self-defense capacity of Agaricus bisporus by UV-C treatment.

Agaricus bisporus (A. bisporus) with completely white appearance are popular with consumers. However, A. bisporus are easily senescence and spoilt, which results in browning and oxidative tissue damage with limited shelf life. This study investigated the effects of shortwave ultraviolet (UV-C, 1.0 kJ m-2 ) irradiation on quality features, enzymatic browning, defense properties of A. bisporus stored at 4 °C for 21 d. After storage, UV-C irradiated A. bisporus had increased quality on sensory, color, hardness, exhibited higher content in total phenolic, brown melanin precursors, including γ-glutaminyl-4-hydroxybenzene (GHB), γ-glutaminyl-3,4-dihydroxybenzene (GDHB) and tyrosine content, lower accumulation of malondiadehyde (MDA), hydrogen peroxide (H2 O2 ), superoxide radical (O2 •¯ ) and maintained membrane integrity in comparison to control samples. Besides, A. bisporus treated by UV-C showed lower degree of browning and higher level of self-defense capacity which may be ascribed to the enhancement in activities of superoxide dismutase (SOD), catalase (CAT), phenylalanine ammonia lyase (PAL), Chitinase (CHT), β-1, 3 glucanase activity (GLU) and inhibiting the activities of polyphenol oxidase (PPO) during the storage. These results indicated that the higher self-defense capacity with UV-C treatment might be the mechanism associated with the delay of senescence in Agaricus bisporus. Therefore, the UV-C treatment is suggested as a potential practical application in mushrooms. This article is protected by copyright. All rights reserved.

Effects of upadacitinib and PD29 on oxidative damage and inflammation in bleomycin-induced scleroderma model kidney tissues

Objective: Scleroderma (SSc) is a rare autoimmune tissue disease. There is currently no effective treatment for SSc. The aim of this
 study was to investigate the antioxidant and anti-inflammatory effects of upadacitinib and PD29 on total oxidant status (TOS), total
 antioxidant status (TAS), malondialdehyde (MDA), catalase (CAT), glutathione (GSH) peroxidase levels, and interleukin-6 (IL-6) and
 interleukin-13 ( IL-13) in kidney tissues of an experimental SSc model.
 Materials and Methods: The experimental design was established with five groups of eight mice: Control, bleomycin (BLM) (5 μg/kg),
 BLM + upadacitinib (3mg/kg), BLM + PD29 (5 mg/kg) and BLM + PD29 + upadacitinib group. BLM was administered subcutaneously
 once a day for 21 days. PD29 was administered subcutaneously and upadacitinib (gavage) were injected for 21 days. Renal tissues were
 collected at the end of the experiment. Renal TOS, TAS, MDA, CAT, GSH levels, and IL-6 and IL-13 gene expressions were evaluated.
 Results: Upadacitinib and PD29 affected oxidant status and TOS. MDA levels decreased, and GSH, CAT, and TAS levels increased.
 Also, upadacitinib and PD29 decreased inflammation via IL-6 and IL-13 cytokines.
 Conclusion: Upadacitinib and PD29 may have therapeutic roles for SSc renal crisis.

Interleukin-35 and Thymoquinone nanoparticle-based intervention for liver protection against paracetamol-induced liver injury in rats

Paracetamol (PAR) is a commonly used antipyretic and analgesic agent, but its excessive usage can induce liver damage and major health consequences. Interleukin-35 (IL-35) is utilized to treat immunological disorders, intestinal illness, arthritis, allergic disease, hepatitis, and cancer. Thymoquinone (THYO) is also effective against a wide range of disorders. Consequently, this study sought out to explore the ameliorative effects of IL-35 and THYO against PAR-induced hepatotoxicity in rats. Sixty male rats were separated into six groups (10 rats/group): I control (0.5 mL NaCl, 0.9%/rat via oral gavage); II (IL-35), and III (TYHO) received intraperitoneal (i.p) injection of IL-35 (200 ng/kg) or THYO (0.5 mg/kg), respectively. Group IV (PAR) received 600 mg/kg of PAR orally; V (PAR + IL-35) and VI (PAR + TYHO); rats received 600 mg/kg of PAR orally and i.p injection of IL-35 (200 ng/kg) or THYO (0.5 mg/kg), respectively. Administration of IL-35 or THYO markedly mitigated the increasing in the levels of liver parameters triggered by PAR and noticeable enhancement of antioxidant and immunological markers were observed. Additionally, IL-35 or THYO decreased TNF-α, NF-κB, IL-10, IL-6 and IFN-γ in contrast to the PAR control group. Moreover, levels of Capase-3, and cytochrome C were significantly reduced by THYO or IL35, while, levels of Bcl-2 were markedly increased. Furthermore, significant downregulation of IL1-β, TNF-α, TGF-β, and Caspas-3 genes, as well as significant upregulation of Bcl-2 and IL-10 expression were detected. In conclusion, IL-35 and THYO insulated liver from PAR toxicity by mitigating oxidative stress, tissue damage, inflammation, and apoptosis.

Effect of celecoxib on intra-abdominal sepsis-induced lung injury in rats

Objectives: This experimental study investigated the preventive effects of Celecoxib, a selective COX-2 inhibitor, on lung injury induced by intra-abdominal sepsis in rats. The study assessed Celecoxib's potential to mitigate the harmful impacts of sepsis on lung tissue. Methods: Thirty male Wistar albino rats, divided into three groups: a normal control group, a sepsis-induced group treated with saline, and a sepsis-induced group treated with Celecoxib. Sepsis was induced using fecal intraperitoneal injection (FIP), followed by a one-hour administration of Celecoxib at 50 mg/kg/day to the treatment group. Biochemical analysis of lung tissue measured oxidative stress markers (malondialdehyde [MDA]) and pro-inflammatory cytokines (Tumor Necrosis Faftor-α [TNF-α]). Histopathological examination evaluated lung tissue damage, encompassing alveolar congestion, hemorrhage, inflammatory cell aggregation, and edema. Arterial blood gas analysis quantified partial oxygen (PaO2) and carbon dioxide (PaCO2) pressures. Results: Celecoxib-treated rats exhibited reduced oxidative stress markers with lower MDA levels, indicating decreased oxidative damage in lung tissue. Moreover, TNF-α and other pro-inflammatory cytokines were significantly reduced in lung tissues of Celecoxib-treated rats, indicating its anti-inflammatory effects. Histopathological examination revealed reduced lung tissue damage in Celecoxib-treated rats, including alveolar congestion, hemorrhage, and inflammatory cell aggregation. Arterial blood gas analysis showed improved oxygenation (PaO2) in the Celecoxib-treated group compared to untreated sepsis rats. Conclusions: Celecoxib demonstrated preventive effects against sepsis-induced lung injury in rats by mitigating oxidative stress and inflammation, thereby preserving lung tissue integrity—further research, including clinical trials, to validate its effectiveness and safety in human sepsis management.

The effect of TEMPOL pretreatment on postoperative cognitive function, inflammatory response, and oxidative stress in aged rats under sevoflurane anesthesia.

The heterocyclic compound 4-hydroxy-(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPOL) has a protective effect on neurological function in brain tissues damaged by ischemia and hypoxia. This study explored the effects of TEMPOL pretreatment on postoperative cognitive function in aged rats under sevoflurane anesthesia, focusing on inflammatory response and oxidative stress. Sixty male rats were divided into normal control (C), sevoflurane anesthesia (S), TEMPOL pretreatment (T), and sevoflurane anesthesia + TEMPOL pretreatment (ST) groups (15 per group). Groups T and ST rats received continuous intraperitoneal TEMPOL (100 mg/kg) for 3 days, while groups C and S rats were injected with 0.9% saline. After pretreatment, groups S and ST received 3% sevoflurane anesthesia. Rats in group S exhibited a longer swimming distance, longer escape latency, lower frequency of platform crossing, and shorter dwell time in the targeted quadrant than those in groups C and T. Rats in group ST exhibited a shorter swimming distance, shorter escape latency, higher frequency of platform crossing, and longer dwell time in the targeted quadrant than those in group S. The expressions of interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, and Ym1/2 messenger ribonucleic acid were higher in groups S and ST rats than in groups C and T rats and lower in group ST rats than in group S rat (p < .05). Superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) were lower, while malondialdehyde (MDA) was higher in groups S and ST rats than in groups C and T rats (p < .05). Group ST showed higher SOD, T-AOC, and GSH-Px, and lower MDA than group S (p < .05). TEMPOL pretreatment attenuated postoperative cognitive impairment induced by sevoflurane anesthesia in aged rats. This may be attributed to the downregulation of NR2B-CREB-BDNF pathway, reducing the inflammatory response and oxidative stress damage in hippocampal tissue.

P19-03: Oxidative damage in liver tissue induced by low doses exposure to a mixture of lead and polychlorinated biphenyls: Subacute toxicity study in rats

P19-03: Oxidative damage in liver tissue induced by low doses exposure to a mixture of lead and polychlorinated biphenyls: Subacute toxicity study in rats

Harmfulness of prooxidants in bronchopulmonary dysplasia in preterm children

Introduction. Oxidative stress can be defined as the imbalance of the redox state of a certain system including living one (organelle, cell, organ/tissue), which excessively produces reactive oxygen and/or reactive nitrogen species (ROS/RNS) that exceed the capacity of the antioxidant defense system, which have the ability to slow down or even prevent the oxidative damage of macromolecules. Oxidative stress is a pathogenic mechanism of a large variety of diseases, including pulmonary one. Material and methods. 81 preterm born children included in the study were divided into the main group – preterm children with bronchopulmonary dysplasia (BPD), and the control group – preterm children without BPD. The comparison groups were prospectively evaluated clinical, instrumental and laboratory (TPA, prooxidant-antioxidant balance, nitric oxide metabolistes and MDA). Data were statistically analyzed using Microsoft Excel, MedCalc and SPSS and Contingency Table Analysis as a way to evaluate the performance of a diagnostic test. Results. In preterm children with BPD were found to be decreased by 29% (p &lt; 0.001) the prooxidant-antioxidant balance (PAB) and the nitric oxide metabolistes (NO) level by 12% (p &lt; 0.001) compared to children in the control group. The assessment of tissue oxidative damage markers revealed a significant 62% (p &lt; 0.001) increase in malonic dialdehyde (MDA) content and a 4.86-fold (p &lt; 0.001) increase in total prooxidant activity (TPA) in children with bronchopulmonary dysplasia compared to children in the control group. Our study confirms that TPA, PAB, MDA and NO values are reliable markers of hypoxic tissue damage at children with bronchopulmonary dysplasia and can be recommended for assessing the intensity of oxidative stress. Conclusions. Pulmonary bronchodysplasia is characterized by the imbalance of prooxidant-antioxidant processes with the exacerbation of prooxidant ones that trigger the oxidative/nitrosative stress and the deterioration of vital chemical compounds.

Iron Chelation Property, Antioxidant Activity, and Hepatoprotective Effect of 6-Gingerol-Rich Ginger (Zingiber officinale) Extract in Iron-Loaded Huh7 Cells.

Iron is essential for numerous biological processes; however, an iron imbalance can contribute to a number of diseases. An excess of iron can accumulate in the body and subsequently induce the production of reactive oxygen species (ROS), leading to oxidative tissue damage and organ dysfunction. The liver, a major iron storage site, is vulnerable to this iron-induced oxidative damage; however, this issue can be overcome by the chelation of excess iron. This study aimed to investigate the effect of 6-gingerol-rich ginger (Zingiber officinale) extract on iron chelation, antioxidation, and hepatoprotective function in protecting against iron-induced oxidative liver cell injury. In experiments, 6-gingerol was confirmed to be a main bioactive component of the ginger extract and possessed free radical scavenging activity, decreasing ABTS•+ and DPPH• radical levels, and inhibiting AAPH-induced red blood cell hemolysis. Interestingly, the extract significantly reduced the levels of labile cellular iron (LCI), intracellular ROS, and lipid peroxidation products (TBARS) in iron-loaded human hepatoma (Huh7) cells. In conclusion, this work highlights the iron chelation property of 6-gingerol-rich ginger extract and its antioxidant activity, which could potentially protect the liver from iron-induced oxidative tissue damage.

Phaseolus vulgaris and Pisum sativum, representing ureide and amide legumes respectively, exploit ureides differentially to mitigate the deleterious effects of cadmium toxicity

PurposeUreides, allantoin and allantoate, are N-rich compounds used for N transport in nodulated ureide legumes. Here, we investigated their role in response of Phaseolus vulgaris and Pisum sativum, representing ureide and amide legumes, respectively, to Cd toxicity.MethodsFirst, ureide content and ureide metabolism in P. vulgaris and P. sativum grown under control conditions and treated with 50 μM CdCl2 for 48 hours was investigated. Then, the effect of exogenous allantoin and its precursor, uric acid, on Cd-related oxidative lesion was examined in both legumes.ResultsCd increased the content of both ureides only in the leaves of P. vulgaris, which was consistent with transcript levels and activity of ureide metabolic enzymes, and was accompanied by an increase in uric acid content. In P. sativum leaves, Cd increased the activity of ureide biosynthesis enzymes and decreased the activity of ureide degradation enzymes, although the uric acid content did not change, while the allantoin and allantoate contents were significantly reduced. Exogenous uric acid and allantoin suppressed Cd-induced H2O2 and O2 accumulation and alleviated the effects of oxidative damage measured by RNA degradation, chlorophyll and malondialdehyde content in both legumes.ConclusionsP. sativum use allantoin and uric acid as antioxidant agents to mitigate Cd-related oxidative tissue damage. In P. vulgaris, the involvement of the ureide pathway in Cd-induced N salvage and recycling is rather a priority.

1,3-Butanediol Administration Increases β-Hydroxybutyrate Plasma Levels and Affects Redox Homeostasis, Endoplasmic Reticulum Stress, and Adipokine Production in Rat Gonadal Adipose Tissue.

Ketone bodies (KBs) are an alternative energy source under starvation and play multiple roles as signaling molecules regulating energy and metabolic homeostasis. The mechanism by which KBs influence visceral white adipose tissue physiology is only partially known, and our study aimed to shed light on the effects they exert on such tissue. To this aim, we administered 1,3-butanediol (BD) to rats since it rapidly enhances β-hydroxybutyrate serum levels, and we evaluated the effect it induces within 3 h or after 14 days of treatment. After 14 days of treatment, rats showed a decrease in body weight gain, energy intake, gonadal-WAT (gWAT) weight, and adipocyte size compared to the control. BD exerted a pronounced antioxidant effect and directed redox homeostasis toward reductive stress, already evident within 3 h after its administration. BD lowered tissue ROS levels and oxidative damage to lipids and proteins and enhanced tissue soluble and enzymatic antioxidant capacity as well as nuclear erythroid factor-2 protein levels. BD also reduced specific mitochondrial maximal oxidative capacity and induced endoplasmic reticulum stress as well as interrelated processes, leading to changes in the level of adipokines/cytokines involved in inflammation, macrophage infiltration into gWAT, adipocyte differentiation, and lipolysis.

18-α-glycyrrhetinic acid alleviates oxidative damage in periodontal tissue by modulating the interaction of Cx43 and JNK/NF-κB pathways.

Objective: Periodontitis is a common chronic inflammatory disease in which oxidative stress is one of the key pathogenic factors. Connexin43 (Cx43) is the most critical and widely distributed connexin isoform. When the organism undergoes a severe and sustained stress response, Cx43-mediated gap junctions (GJs) are believed to underlie the biology of tissue injury exacerbation and amplification. Notably, 18-α-glycyrrhetinic acid (GA) is a classical pharmacological inhibitor of GJs and has antioxidant potential. However, the regulatory role of GA in the redox signaling of periodontal tissues and the potential mechanisms of Cx43 in the pathogenesis of periodontitis remain uncertain. Methods: In this study, we evaluated the effects and mechanisms of GA in alleviating oxidative damage of periodontal tissues and cells by constructing an H2O2-induced oxidative stress model in human periodontal ligament cells (hPDLCs) and a periodontitis model in rats. Results: Cellular experiments showed that GA effectively attenuated H2O2-induced oxidative damage in hPDLCs by inhibiting the expression and function of Cx43. In addition, pretreatment of hPDLCs with either GA or SP600125 (a JNK inhibitor) inhibited the Cx43/JNK/NF-κB pathway, restored cell viability, and reduced apoptosis. Animal experiment results showed that GA intervention reduced alveolar bone resorption and periodontal tissue destruction, inhibited osteoclast differentiation, improved mitochondrial structural abnormalities and dysfunction in periodontal tissue, and decreased oxidative stress levels and apoptosis in rats with periodontitis. Conclusion: Overall, our findings suggest that the Cx43/JNK/NF-κB pathway may play a vital role to promote periodontitis progression, while GA reduces oxidative stress and apoptosis by inhibiting the interaction of Cx43 and JNK/NF-κB pathways, thus alleviating oxidative damage in the periodontal tissues.

Ameliorative potential of the quercetin on lead-induced testicular damage: morphohistometric and biochemical analysis

BackgroundQuercetin, a naturally occurring flavonoid known for its potent antioxidant properties, has been investigated for its potential in counteracting the harmful effects of lead (Pb) toxicity, which induces apoptosis and oxidative damage in various human tissues. This study aims to assess the reparative effects of quercetin on lead-induced testicular damage.MethodsFour groups, each comprising ten adult male albino rats, were randomly assigned as follows: Quercetin group, Pb group, Pb + Quercetin group, and control group. All treatments were administered orally via gavage daily for a duration of 30 days. Evaluation of sex hormone levels (serum testosterone, FSH, and LH), cytokines and inflammatory mediators (IL-1β, TNF-α, MCP-1), lead concentration, oxidative and antioxidant stress markers (superoxide anion [O2−], MDA, SOD, CAT, GSH), and sperm characteristics were carried out.ResultsThe results demonstrated a significant decline in sex hormones and antioxidants, accompanied by an increase in lead concentrations, cytokines, inflammatory mediators, and oxidative stress indicators (O2−, MDA), while SOD, CAT, and GSH levels were reduced. The Pb-intoxicated group exhibited a substantial increase in dead and abnormal sperm, along with significant reductions in sperm concentration and motility. Morphometrically, a marked decrease was observed in spermatogonia, primary spermatocytes, spermatids, and sertoli cells per seminiferous tubule, as well as epithelial height. Furthermore, coadministration of quercetin exhibited notable benefits. It significantly elevated testosterone levels (P < 0.001), testicular SOD, CAT, and GSH activities, while decreasing MDA levels (P < 0.001). Quercetin also mitigated the deleterious effects of lead toxicity on sperm parameters and restored morphometric variations, including epithelial height.ConclusionsQuercetin supplementation alongside lead exposure showed a potential for ameliorating degenerative changes caused by lead toxicity in the testicles. This cotreatment effectively reduced oxidative stress, cytokine levels, inflammatory mediators, and restored biochemical alterations, thereby improving morphometric parameters.

The protective effects of chrysin on cadmium-induced pulmonary toxicity; a multi-biomarker approach.

This study aimed to determine the potential protective effects of chrysin (CHR) on experimental cadmium (Cd)-induced lung toxicity in rats. To this end, rats were divided into five groups; Control, CHR, Cd, Cd + CHR25, Cd + CHR50. In the study, rats were treated with CHR (oral gavage, 25mg/kg and 50mg/kg) 30min after giving Cd (oral gavage, 25mg/kg) for 7 consecutive days. The effects of Cd and CHR treatments on oxidative stress, inflammatory response, ER stress, apoptosis and tissue damage in rat lung tissues were determined by biochemical and histological methods. Our results revealed that CHR therapy for Cd-administered rats could significantly reduce MDA levels in lung tissue while significantly increasing the activity of antioxidant enzymes (SOD, CAT, GPx) and GSH levels. CHR agent exerted antiinflammatory effect by lowering elevated levels of NF-κB, IL-1β IL-6, TNF-α, RAGE and NRLP3 in Cd-induced lung tissue. Moreover CHR down-regulated Cd-induced ER stress markers (PERK, IRE1, ATF6, CHOP, and GRP78) and apoptosis markers (Caspase-3, Bax) lung tissue. CHR up-regulated the Bcl-2 gene, an anti-apoptotic marker. Besides, CHR attenuated the side effects caused by Cd by modulating histopathological changes such as hemorrhage, inflammatory cell infiltration, thickening of the alveolar wall and collagen increase. Immunohistochemically, NF-κB and Caspase-3 expressions were intense in the Cd group, while these expressions were decreased in the Cd + CHR groups. These results suggest that CHR exhibits protective effects against Cd-induced lung toxicity in rats by ameliorating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress and histological changes.

Xanthine oxidoreductase gene polymorphisms are associated with high risk of sepsis and organ failure

BackgroundSepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis.MethodsWe genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets.ResultsAmong AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P < 0.008–0.049). Two out of six SNPs (rs561525 and rs2163059) were associated with risk of sepsis-associated ARDS in an independent validation cohort (GEN-SEP) of 590 sepsis patients of European descent. Two common SNPs (rs1884725 and rs4952085) in tight linkage disequilibrium (LD) provided strong evidence for association with increased levels of serum creatinine (Padjusted<0.0005 and 0.0006, respectively), suggesting a role in increased risk of renal dysfunction. In contrast, among EA ARDS patients, the missense variant rs17011368 (I703V) was associated with enhanced mortality at 60-days (P < 0.038). We found higher serum XOR activity in 143 sepsis patients (54.5 ± 57.1 mU/mL) compared to 31 controls (20.9 ± 12.4 mU/mL, P = 1.96 × 10− 13). XOR activity was associated with the lead variant rs185925 among AA sepsis patients with ARDS (P < 0.005 and Padjusted<0.01). Multifaceted functions of prioritized XDH variants, as suggested by various functional annotation tools, support their potential causality in sepsis.ConclusionsOur findings suggest that XOR is a novel combined genetic and biochemical marker for risk and outcome in patients with sepsis and ARDS.

Olea europaea L. leaf extract mitigates oxidative and histological damage in rat heart tissue exposed to combined noise and toluene: An experimental study

In many occupational settings, workers are frequently exposed to toluene and noise. However, the individual and combined effects of these exposures on the cardiovascular system have not been fully elucidated. Therefore, this study aimed to investigate the impact of simultaneous exposure to toluene and noise on the rat heart, while also evaluating the potential preventive effect of olive leaf extract (OLE). Forty-eight male Wistar rats were randomly assigned to eight groups (n = 6/group): control group (C), control group that received OLE (C + OLE), group exposed to noise (N), group exposed to noise and receiving OLE (N + OLE), group exposed to toluene (T), group exposed to toluene and receiving OLE (T + OLE), group co-exposed to noise and toluene (NT), and group co-exposed to noise and toluene and receiving OLE (NT + OLE). The rats in this study were subjected to simultaneous exposure to toluene and noise for a duration of six weeks, within a custom-built plexiglass chamber. Toluene was administered at a concentration of 300 ppm, while the noise level was set to 85 dB(A). The exposure chamber was equipped with a generation system, an exposure system, and a monitoring system, ensuring precise and accurate exposure conditions. After the six-week period, heart and blood samples were collected from the rats for subsequent analysis. Plasma levels of cholesterol (CHOL), triglycerides (TG), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured, and histopathological investigation was conducted using HE staining. Additionally, superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) levels in heart tissue were measured. Our results showed that simultaneous exposure to noise and toluene altered CHOL, TG, LDH, and CK levels, and also caused an increase in lipid peroxidation levels and superoxide dismutase activity, along with a decrease in catalase activity in the heart. A significant alteration in the myocardium was also observed. However, treatment with OLE was found to modulate these oxidative and histological changes, ultimately correcting the deleterious effects induced by the combined exposure to noise and toluene. Therefore, our study suggests that OLE could be a potential preventive measure for individuals exposed to toluene and noise in industrial settings.

L-Carnitine Prevents Behavioural Alterations in Ketamine-Induced Schizophrenia in Mice: Possible Involvement of Oxidative Stress and Inflammation Pathways.

Schizophrenia is a chronic mental complaint known as cognitive impairment. There has been evidence that inflammation and oxidative stress play a main role in schizophrenia pathophysiology. This study aimed to investigate the effects of l-carnitine, as a potent antioxidant, on the treatment of behavioural and biochemical disturbances in mice with ketamine-induced schizophrenia. In this study, schizophrenia was induced in mice by ketamine (25 mg/kg/day, i.p). Before induction of schizophrenia, mice were treated with l-carnitine (100, 200, and 400 mg/kg/day, i.p). Then, behavioural impairments were evaluated by open field (OF) assessment and social interaction test (SIT). After brain tissue isolation, reactive oxygen species (ROS), glutathione concentration (GSH), lipid peroxidation (LPO), protein carbonyl oxidation, superoxide dismutase activity (SOD), and glutathione peroxidase activity (GPx) were assessed as oxidative stress markers. Furthermore, inflammatory biomarkers such as tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) were evaluated in brain tissue. Our results showed ketamine increased inflammation and oxidative damage in brain tissue that was similar to behaviour disorders in mice. Interestingly, l-carnitine significantly decreased oxidative stress and inflammatory markers compared with ketamine-treated mice. In addition, l-carnitine prevented and reversed ketamine-induced alterations in the activities of SOD and GPx enzymes in mice's brains. Also, improved performance in OFT (locomotor activity test) and SIT was observed in l-carnitine-treated mice. These data provided evidence that, due to the antioxidant and anti-inflammatory effects of l-carnitine, it has a neuroprotective effect on mice model of schizophrenia.