8-OHdG Expression Research Articles

Anchoring of Nanocomposites Based on Novel Metal Nanocomplexes/Nanocarbonaceous Surfaces and Assessing Their In Vivo Anticancer Effects on Ehrlich Ascites Tumor.

Nanotechnology is the study of materials' unique properties at the nanoscale. Nanomedicine is the application of nanotechnology in medicine, which has been utilized to treat some common diseases, such as cancer. The aim of the present work is to synthesize the cadmium (Cd) nanocomplex using paracetamol as a ligand with a molar ratio of 1:2 M/L that was characterized by different physicochemical methods and to explore the effect of the synthesized Cd nanocomplex on the immune system and the redox status of the body and their anticancer effects on Ehrlich ascites carcinoma (EAC) induced in mice. Eighty female albino mice were separated into Group I: control; Group II: EAC; Group III: EAC treated with a low-dose Cd nanocomplex; and Group IV: EAC treated with a high-dose Cd nanocomplex. Interleukin-6 (IL-6), NLR family pyrin domain containing 3 (NLRP3), and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels were assessed by enzyme-linked immunosorbent assay (ELISA). Peroxynitrite level and glutathione peroxidase activity were assessed by spectrophotometry. NRF2 mRNA expression, cadmium content, and liver and renal toxicity were estimated. Results: There was a significant increase in IL-6, NLRP3, 8-OHdG, peroxynitrite, and NRF2 mRNA expressions and in the glutathione peroxidase activity in EAC treated with low- and high-dose Cd nanocomplexes. However, the EAC treated with high-dose Cd nanocomplex group showed significant liver and renal toxicity. Conclusion: Cadmium nanocomplex has anticancer effects on EAC induced in mice via its effects on the immune system and redox status as well as pyroptosis and epigenetic instability of the body, while high doses of Cd nanocomplex can cause liver and renal toxicity.

Bisphenol A impairs renal function by reducing Na+/K+-ATPase and F-actin expression, kidney tubule formation in vitro and in vivo

The kidney proximal tubule is responsible for reabsorbing water and NaCl to maintain the homeostasis of the body fluids, electrolytes, and nutrients. Thus, abnormal functioning of the renal proximal tubule can lead to life-threatening imbalances. Bisphenol A (BPA) has been used for decades as a representative chemical in household plastic products, but studies on its effects on the kidney proximal tubule are insufficient. In this study, immunocytochemical and cytotoxicity tests were performed using two- and three-dimensional human renal proximal tubular epithelial cell (hRPTEC) cultures to investigate the impact of low-dose BPA (1–10 μM) exposure. BPA was found to interfere with straight tubule formation as observed by low filamentous actin formation and reduced Na+/K+-ATPase expression in the tubules of hRPTEC 3D cultures. Similar results were observed in rat pup kidneys following oral administration of 250 mg/kg BPA. Moreover, the expression of HO-1 and 8-OHdG, key markers for oxidative stress, was increased in vitro and in vivo following BPA administration, whereas that of OAT1 and OAT, important transporters of the renal proximal tubules, was not altered. Overall, no-observed-adverse-effect-level (NOAEL)-dose BPA exposure can decrease renal function by promoting abnormal tubular formation both in vitro and in vivo. Therefore, we propose that although it does not exhibit life-threatening toxicity, exposure to low levels of BPA can negatively affect homeostasis in the body by means of long-term deterioration of renal proximal tubular function in humans.

Maternal hypothyroidism causes oxidative stress and endoplasmic reticulum stress in the maternal-fetal interface of rats.

Maternal hypothyroidism is associated with pre-eclampsia and intrauterine growth restriction, gestational diseases involving oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the placenta. However, it is not known whether hypothyroidism also causes OS and ERS at the maternal-fetal interface. The aim was to evaluate the fetal-placental development and the expression of mediators of OS and of the unfolded protein response (UPR) in the maternal-fetal interface of hypothyroid rats. Hypothyroidism was induced in Wistar rats with propylthiouracil and the fetal-placental development and placental and decidual expression of antioxidant, hypoxia, and UPR mediators were analyzed at 14 and 18 days of gestation (DG), as well the expression of 8-OHdG and MDA, and reactive oxygen species (ROS) and peroxynitrite levels. Hypothyroidism reduced fetal weight at 14 and 18 DG, in addition to increasing the percentage of fetal death and reducing the weight of the uteroplacental unit at 18 DG. At 14 DG, there was greater decidual and/or placental immunostaining of Hif1α, 8-OHdG, MDA, SOD1, GPx1/2, Grp78 and CHOP in hypothyroid rats, while there was a reduction in placental and/or decidual gene expression of Sod1, Gpx1, Atf6, Perk, Ho1, Xbp1, Grp78 and Chop in the same gestational period. At 18 DG, hypothyroidism increased the placental ROS levels and the decidual and/or placental immunostaining of HIF1α, 8-OHdG, MDA, ATF4, GRP78 and CHOP, while it reduced the immunostaining and enzymatic activity of SOD1, CAT, GST. Hypothyroidism increased the placental mRNA expression of Hifα, Nrf2, Sod2, Gpx1, Cat, Perk, Atf6 and Chop at 18 DG, while decreasing the decidual expression of Sod2, Cat and Atf6. These findings demonstrated that fetal-placental restriction in female rats with hypothyroidism is associated with hypoxia and dysregulation in placental and decidual expression of UPR mediators and antioxidant enzymes, and activation of oxidative stress and endoplasmic reticulum stress at the maternal-fetal interface.

Effects of maternal fructose intake on the offspring's kidneys.

Fructose overload is associated with cardiovascular and metabolic disorders. During pregnancy, these alterations may affect the maternal environment and predispose offspring to diseases. Aims: To evaluate the renal morphology and function of offspring of dams that received fructose overload during pregnancy and lactation. Methods: Female Wistar rats were divided into the control (C) and fructose (F) groups. C received food and water ad libitum, and F received food and d-fructose solution (20%) ad libitum. The d-fructose offer started 1 week before mating and continued during pregnancy and lactation. The progeny were designated as control (C) or fructose (F); after weaning, half of the F received water to drink (FW), and half received d-fructose (FF). Blood pressure (BP) and renal function were evaluated. The expression of sodium transporters (NHE3-exchanger, NKCC2 and NCC-cotransporters, and ENaC channels) and markers of renal dysfunction, including ED1 (macrophage), eNOS, 8OHdG (oxidative stress), renin, and ACE 1 and 2, were evaluated. CEUA-UNIFESP: 2757270117. The FF group presented with reduced glomerular filtration rate and urinary osmolarity, increased BP, proteinuria, glomerular hypertrophy, macrophage infiltration, and increased expression of transporters (NHE3, NCC, and ENaC), 8OHdG, renin, and ACE1. The FW group did not show increased BP and renal functional alterations; however, it presented glomerular hypertrophy, macrophage infiltration, and increased expression of the transporters (NHE3, NKCC2, NCC, and ENaC), renin, and ACE1. These data suggest that fructose overload during fetal development alters renal development, resulting in the increased expression of renin, ACE1, and sodium transporters, thus predisposing to hypertension and renal dysfunction.

MitoQ demonstrates connexin- and p53-mediated cancer chemoprevention in N-nitrosodiethylamine-induced hepatocarcinogenesis rodent model

Cancer chemoprevention is an approach that offers huge potential for preventing/retarding carcinogenesis. MitoQ is well-known and extensively studied mitochondria-targeted antioxidants for its applications in diseases linked with oxidative stress. In the present study chemopreventive potential of mitoQ was studied with a focus on the role of gap-junctions and p53 at an advanced stage of HCC. BALB/c mice model of hepatocarcinogenesis was established using N-nitrosodiethylamine as a carcinogen (200 mg/kg b. w., cumulative dose, intraperitoneally). The chemopreventive effect of mitoQ was studied by pre-protecting animals with mitoQ (0.125 mg/kg b. w., orally once a week) till the termination of the study. The tumors developed in the course of the study were histopathologically analyzed and statistically evaluated. The mechanistic role of mitoQ was investigated in terms of mitochondrial oxidative stress, expression of 8-OHdG, Cx26, Cx32, p53 and status of gap-junctional intercellular communication (GJIC) in tumors. Chemopreventive activity of mitoQ was evident from improved survival of animals, significantly (p ≤ 0.05) lower tumor multiplicity, tumor incidence and a total number of tumors. MitoQ treatment significantly (p ≤ 0.05) decreased mitochondrial oxidative stress as indicated by reduced mtROS and mtLPO. Increased staining intensity of 8-OHdG and internalization of Cx26, Cx32 which was observed in hepatic tumors was reduced upon mitoQ treatment. Furthermore, the expression of Cx26, Cx32 and p53 was significantly increased along with improvement in GJIC in mitoQ treatment group. MitoQ demonstrated its chemopreventive potential probably by regulating mtROS, connexins and p53 in hepatocarcinogenesis.

Protective effects of L-arginine against aluminium chloride-induced testicular damage in rats.

Aluminium (Al) is a toxic metal with frequent exposure because it is a common element in nature and is found in many products used in daily life. L-arginine is a semi-essential amino acid that is involved in many biochemical pathways in the body and has antioxidant effects. The current research evaluated the possible protective effects of L-arginine against aluminium chloride (AlCl3 ) induced testicular damage. In this animal-based experimental study, 28 male Wistar Albino rats were separated into four groups: control, Al (20 mg/kg/day Al), Al + L-arginine (20 mg/kg/day Al + 50 mg/kg/day L-arginine), and L-arginine (50 mg/kg/day L-arginine). All applications were carried out intraperitoneally (i.p.) for 4 weeks. The histopathological changes caused by exposure to Al in the testicular tissue and the protective effects of L-arginine were investigated by using biochemical, histochemical, immunohistochemical [4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG)] and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay techniques. The testicles in the AlCl3 group showed increased 4-HNE, 8-OHdG expressions, apoptotic index, and abnormal sperm content, while serum testosterone levels, sperm motility, and sperm number were decreased (p < 0.05). Furthermore, histomorphometric examinations of testicular tissue indicated significant structural impairments such as vacuolization in the seminiferous tubule epithelium, edema, and vascular congestion in the interstitial area (p < 0.05). However, the structural alterations were largely ameliorated in the Al + L-arginine group (p < 0.05). Thus, L-arginine, which is an antioxidant, may protect against the harmful effects of Al and may help improve male fertility.

Effect of Fluoride on the Expression of 8-Hydroxy-2'-Deoxyguanosine in the Blood, Kidney, Liver, and Brain of Rats.

Excessive exposure of fluoride not only leads to damage on bone, but also has an adverse effect on soft tissues. Oxidative DNA damage induced by fluoride is thought to be one of the toxic mechanisms of fluoride effect. However, the dose-response of fluoride on oxidative DNA damage is barely studied in organisms. This study investigated the concentration of fluoride in rat blood, kidney, liver, and brain as well as the dose-time effect of fluoride on the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the above tissues. Rats were exposed to 0mg/L, 25mg/L, 50mg/L, and 100mg/L of fluorine ion and treated for one and three months. The results showed that the accumulation of fluoride in soft tissues was very different. At the first month, blood fluoride was increased, liver and brain fluoride showed a U-shaped change, and kidney fluoride was not significant. At the third month, blood fluoride was altered with an inverted U-shaped change, kidney and brain fluoride increased, but liver fluoride decreased. Both the exposure concentration and the time of exposure had a significant effect on the expression of 8-OHdG in the above tissues. However, the effect patterns of fluoride on these tissues were notably different at different times. At the first month of fluoride treatment, blood, kidney, and liver 8-OHdG decreased with the increasing fluoride concentration. At the third month, blood 8-OHdG showed a U-shaped change, but kidney 8-OHdG altered with an inverted U-shaped change. Liver 8-OHdG increased, while brain 8-OHdG decreased at the third month. Correlation analysis showed that only blood 8-OHdG was significantly inversely correlated with blood fluoride and dental fluorosis grade in both the first and third months. Liver 8-OHdG was negatively and significantly correlated with liver fluoride. There was a weak but nonsignificant correlation between kidney and brain 8-OHdG and fluoride in both tissues. Additionally, blood 8-OHdG was positively correlated with kidney and liver 8-OHdG at the first month and positively correlated with brain 8-OHdG at the third month. Taken together, our data suggests that concentration and time of fluoride exposure had a significant effect on 8-OHdG, but the effect patterns of fluoride on 8-OHdG were different in the tissues, which suggests that the impact of fluoride on 8-OHdG may be a tissue-specific, as well as a non-monotonic positive correlation.

ASSOCIATION OF IMMUNOHISTOCHEMICAL EXPRESSION OF 8OHDG WITH THE PATHOGENESIS ACTINIC CHEILITIS

<h3>Objectives</h3> The aim of this study was to investigate the immunohistochemical expression of 8-OHdG in 57 cases of actinic cheilitis (AC) and its association with clinicopathologic parameters. <h3>Study Design</h3> The expression of 8-OHdG was evaluated semiquantitatively and the data were analyzed using the nonparametric Mann-Whitney and Kruskal-Wallis tests to identify statistically significant differences in the expression of 8-OHdG according to the World Health Organization histopathologic grading of oral epithelial dysplasia in the AC samples analyzed. <h3>Results</h3> Most cases exhibited strong immunoreactivity to the anti-8-OHdG antibody (64.9%). No significant differences were observed in the expression of 8-OHdG according to the clinical characteristics of AC or between the different degrees of epithelial dysplasia (<i>P</i> = .35). <h3>Conclusions</h3> The strong immunoexpression of 8-OHdG regardless of the morphologic severity of AC demonstrates the participation of oxidative DNA damage in the pathogenesis of this condition.

OXIDATIVE DNA DAMAGE IN ORAL LEUKOPLAKIA AND ITS ROLE IN THE ORAL CARCINOGENESIS

<h3>Objectives</h3> To evaluate oxidative DNA damage (8-hydroxy-2′-deoxyguanosine [8-OHdG]) and its repair by the base excision repair pathway (Redox factor-1 [Ref-1]; X-ray Repair Cross Complementing-1 [XRCC-1]) in oral leukoplakia (OL) with different degrees of epithelial dysplasia (ED). <h3>Study Design</h3> Forty-four cases of OL and 10 normal oral mucosa (NOM) were evaluated quantitatively for 8-OHdG, Ref-1, and XRCC-1 by immunohistochemistry. <h3>Results</h3> Cytoplasmic 8-OHdG expression was significantly associated with multiple synchronous lesions (<i>P</i> = .048). A significantly gradual cytoplasmic 8-OHdG increase was observed between NOM and ED (<i>P</i> < .05). Nuclear Ref-1 expression was significantly lower (<i>P</i> = .004) in nondysplasia/mild ED, whereas its cytoplasmic expression was higher in nondysplasia/mild ED and moderate/severe ED compared to NOM (<i>P</i> = .03, <i>P</i> < .0001, respectively). Significantly higher cytoplasmic XRCC-1 expression in OL (<i>P</i> < .0001) was observed. <h3>Conclusions</h3> 8-OHdG plays a role in the onset of multiple synchronous OL and the severity of ED. The subcellular level of Ref-1 implies different roles according to the ED degree. Cytoplasmic XRCC-1 expression indicates a DNA repair mechanism failure during oral carcinogenesis.

Topical Curcumin as Chemoprotector Against Photoproducts Production: The Role of Cyclobutyl Pyrimidine Dimers, 8-Hydroxy2'Deoxyguanosine Expression and Epidermal Hyperplasia in Acute and Chronic UVB-Induced Mice.

BackgroundUltraviolet B (UVB) exposure leads to formation of photoproducts leading to cellular damage. Prevention using sunscreen can sometimes be inadequate and can be an economic burden. Recent studies have suggested the photoprotective effect of curcumin.ObjectiveTo examine the acute and chronic photoprotective effect of topical curcumin, using cyclobutyl pyrimidine dimers (CPD) and 8-hydroxy2ʹdeoxyguanosine (8-OHdG) expression as markers of DNA-induced damage, and epidermal hyperplasia on UVB-induced mice.MethodsThree treatment groups were established. Group A (negative control) consisted of 5 mice, Group B and C were further divided into two categories to assess acute and chronic effects of topical curcumin and UVB radiation. Each consisted of six subgroups of five mice. Subgroup 1; UVB exposure only (positive control) subgroup 2; acetone and UVB exposure, subgroup 3–6; topical curcumin application of 100nM, 1µM, 10µM, and 100µM concentrations, respectively. In Group C, there were two categories that received 3x/week UVB exposure for three weeks which effects were being observed at 24 hours and 10 days after the last exposure. The topical curcumin dose was 2mg/mL/cm2 applied 30 minutes prior to 343mJ/cm2/day UVB irradiation. Skin biopsy was done one hour after the last UVB exposure for immunohistochemical and histopathology examinations.ResultsTopical curcumin showed a limited yet robust protective effect against CPD and 8-OHdG expression in Group B, while in Group C all concentrations showed significant CPD and 8-OHdG inhibition after 10 days of UVB exposure. The 10µM and 100µM concentrations showed the best epidermal hyperplasia inhibition effect (p<0.05). No significant differences were found in terms in efficacy either in single nor daily application.ConclusionTopical curcumin can prevent the formation of the photoproducts CPD and 8-OHdG and epidermal hyperplasia in both acute and chronic exposure in UVB-induced mice.

Helicobacter pylori Thioredoxin1 May Play a Highly Pathogenic Role via the IL6/STAT3 Pathway.

Background Recent studies have shown that CagA is considered highly pathogenic to helicobacter pylori (HP) in Western populations. However, in East Asia, CagA positive HP can be up to 90%, but not all patients will lead to gastric cancer. Our research group has found that HP thioredoxin1 (Trx1) may be a marker of high pathogenicity. Here, we investigate whether HP Trx1 exerts high pathogenicity and its internal molecular mechanism. Materials and Methods We constructed the coculture system of high-Trx1 HP and low-Trx1 HP strains with gastric epithelial cell lines separately and detected the influence of HP strains. The cells were stained by AM/PI, and the cell's mortality was assessed by fluorescence microscope. The cell's supernatants or precipitates were collected to detect the expression of IL6. In addition, the cell's precipitates were collected, and the expression of p-STAT3 was detected by western blot. Furthermore, the cell's supernatants were collected for detecting the expression of 8-OHDG to investigate the extent of DNA damage. Results The high-Trx1 HP can cause higher mortality of GES-1 cells compared with the low-Trx1 HP group (high-Trx1 HP (4.53 ± 0.56) %, low-Trx1 HP (0.39 ± 0.10) %, P < 0.001). The mRNA and protein level of IL-6 in AGS and GES-1 cells were increased during HP infection, and the expression of IL-6 in the High-Trx1 HP group was much higher than the low-Trx1 HP group. Besides, the expression of p-STAT3 was higher in the HP-positive gastric mucosa. And the expression of p-STAT3 in the high-Trx1 HP group was significantly upregulated compared with the low-Trx1 HP group. Furthermore, the expression of 8-OHDG in the high-Trx1 group was much higher than the low-Trx1 group (high-Trx1 HP (5.47 ± 1.73) ng/ml, low-Trx1 HP (2.89 ± 1.72) ng/ml, P < 0.05). Conclusion HP Trx1 may play as a marker of high pathogenicity, and the high-Trx1 HP could mediate the pathogenic process of HP infection via the IL6/STAT3 pathway.

Protective Effect of XinJiaCongRongTuSiZiWan on the Reproductive Toxicity of Female Rats Induced by Triptolide.

Background Although triptolide (TP) has been widely used for the treatment of inflammatory, autoimmune diseases, and various kinds of tumors, the long experimental and clinical applications have exhibited severe reproductive system toxicity in TP-treated animals and patients. More importantly, the underlying molecular mechanism involved in TP-induced reproductive system toxicity still needs more research. Methods Adult female Sprague Dawley rats and human ovarian granulosa cell lines were treated with TP and then treated with XinJiaCongRongTuSiZiWan (XJCRTSZW). Histological analysis and follicle count were executed using H&E staining. Hormone (E2, AMH, FSH, LH, and INH B) concentrations, inflammation indicators (IL-1β, IL-6, and TNF-α), oxidative stress indicators (SOD, GSH-Px, and MDA), apoptosis rate, protein distribution and expression (SIRT1, AMPK, and 8-OhdG), cell viability, relative protein levels (beclin-1, LC3-II/LC3-I, p62, procaspase-3, cleaved caspase-3, p-SIRT1, SIRT1, p-AMPKα-1, AMPKα-1, Akt, and p-Akt), autophagosome were detected by ELISA, commercial biochemical detection kits, flow cytometry, immunohistochemistry, CCK-8, western blotting, and transmission electron microscope, respectively. Results XJCRTSZW administration notably improved the TP-treated pathological symptoms, including few mature follicles in the ovary and less granular cell layer, and disordered the arrangement of the follicle, lymphocytes and plasma cells infiltration, and necrosis, shedding, and follicular cystic dilatation of the granular layer follicle cells in the ovarian stroma. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of primary follicles and secondary follicles numbers and decreased the TP-induced elevation of atretic follicle numbers and the expression of AMPK, SIRT1, and 8-OhdG in GCs in vivo. Moreover, XJCRTSZW application significantly increased the TP-induced diminishment of E2, AMH, and LNH-B concentrations, apoptosis rate, SOD and GSH-Px concentrations, and p62 protein level; however, it declined the TP-induced augmentation of MDA level, the levels of IL-1β, IL-6, and TNF-α, autophagosome, beclin-1, LC3-II/LC3-I, cleaved-caspase-3, p-AMPKα-1, and p-SIRT1 protein levels both in vivo and in vitro. Besides, XJCRTSZW treatment prominently enhanced the TP-induced decrease of cell viability in vitro. Conclusion XJCRTSZW can alleviate TP-induced reproductive toxicity via apoptosis, inflammation, and oxidative stress both in vivo and in vitro. Moreover, XJCRTSZW ameliorates TP-induced reproductive toxicity through AMPK/SIRT and Akt signaling axis mediated autophagy both in vivo and in vitro.

Echinacoside Improves Cognitive Impairment by Inhibiting Aβ Deposition Through the PI3K/AKT/Nrf2/PPARγ Signaling Pathways in APP/PS1 Mice

Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer’s disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice treated with ECH in 50 mg/kg/day for 3 months. Morris water maze, nesting test, and immunofluorescence staining used to observe whether ECH could improve AD pathology. Western blot used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress, and inflammatory response in AD. Therefore, we suggest that ECH may considered as a potential drug for AD treatment.

Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells.

We formerly proved that uremic vascular calcification (UVC) correlates tightly with oxidative elastic lamina (EL) injury and two cell fates (apoptosis and osteocytic conversion) in smooth muscle cells (SMC) of chronic kidney disease (CKD) patients and eliminating p-cresyl sulfate (PCS)-activated intracellular ROS ameliorates the MAPK signaling pathway in a human arterial SMC (HASMC) model. Nonetheless, whether ROS scavenger attenuates PCS-triggered inflammasome activation and eicosanoid inflammation in the UVC process remains unknown. Patients with lower extremity amputation were categorized into CKD and normal control group according to renal function. We used immunohistochemistry stain to analyze UVC in arterial specimens, including oxidative injury (8-hydroxy-2′-deoxyguanosine (8-OHdG) and internal EL disruption), cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX2), interleukin-1 beta (IL-1β), caspase-1 and NLRP3. To simulate the patho-mechanism of human UVC, the therapeutic effects of ROS scavenger on PCS-triggered inflammatory pathways was explored in a HASMC model. We found CKD patients had higher circulating levels of PCS and an increase in medial arterial calcification than the control group. In CKD arteries, the severity of UVC corresponded with expressions of oxidative EL disruption and 8-OHdG. Furthermore, coupling expressions of cPLA2 and COX2 were accentuated in CKD arteries, indicative of eicosanoid inflammation. Notably, tissue expressions of IL-1β, caspase-1 and NLRP3 were enhanced in parallel with UVC severity, indicative of inflammasome activation. From bedside to bench, ROS scavenger attenuates PCS-activated expressions of cPLA2/COX2, pro-caspase-1 and NLRP3 in the HASMC model. UVC as an inevitable outcome is predictive of death in CKD patients. Nonetheless, UVC remain pharmacoresistant despite the evolution of treatment for mineral-parathyroid hormone-vitamin D axis. Beyond the mineral dysregulation, the stimulation of pro-oxidant PCS alone results in eicosanoid inflammation and inflammasome activation. Concerning the key role of Caspase-1 in pyroptosis, cell fates of HASMC in uremic milieu are not limited to apoptosis and osteogenesis. In view of this, reducing ROS and PCS may act as a therapeutic strategy for UVC-related cardiovascular events in CKD patients.

Radioprotective effects and mechanism of HL-003 on radiation-induced salivary gland damage in mice

Ionizing radiation (IR) can cause damage to the structure and function of salivary glands. Our research group independently synthesized the ROS scavenger, HL-003. The aim of this study was to explore the protective effects and underlying mechanisms of HL-003 on radiation-induced salivary gland injury. Salivary flow rate measurement, H&E staining, immunohistochemistry, FRAP, TUNEL, and western blotting were used to evaluate the radioprotective effect on salivary glands. The results showed that HL-003 protected the salivary secretion function by protecting the AQP-5 protein, on the salivary epithelial cell membrane, from IR damage. HL-003 reduced oxidative stress in the salivary gland by regulating the expression of ROS-related proteins NOX4, SOD2, and 8-OHdG. Furthermore, HL-003 downregulated the expression of p-p53, Bax, caspase 3, and caspase 9, and upregulated the expression of Bcl-2, suggesting that it could inhibit the activation of p53 to reduce cell apoptosis. In conclusion, HL-003 is an effective radioprotector that prevents damage of the radiation-induced salivary gland.

W252 Levels of lead, cadmium, 8-OHdG and OGG1 expression in occupationally heavy metal exposed population

W252 Levels of lead, cadmium, 8-OHdG and OGG1 expression in occupationally heavy metal exposed population

Propofol Prevents the Growth, Migration, Invasion, and Glycolysis of Colorectal Cancer Cells by Downregulating Lactate Dehydrogenase Both In Vitro and In Vivo

Colorectal cancer (CRC) is one of the most frequently diagnosed gastrointestinal malignancies worldwide and has high rates of morbidity and mortality. Propofol has been reported to have certain anticancer properties. However, the role and mechanism of propofol in CRC are not entirely clear. CRC cells were treated with propofol and/or LDH-overexpression plasmids, and a mouse xenograft model of CRC was also established and treated with propofol. Cell viability, migration, and invasion were evaluated by CCK-8, wound healing, and transwell assays; the expression of related proteins was confirmed by western blotting; indexes of the glycolytic pathway were analyzed using specialized kits; tumor growth in mice was measured; pathological tissue structure was assessed by H&E staining; and 8-OHDG expression was determined by an immunochemistry assay. Our results verified that propofol could effectively prevent the malignant behaviors of CRC cells by suppressing cell viability, migration, and invasion and accelerating apoptosis. We also discovered that propofol could attenuate the glycolytic pathway in CRC cells. Moreover, we proved that lactate dehydrogenase (LDH) was required for the inhibitory effects of propofol on the growth of CRC cells, including glycolysis in CRC cells. Furthermore, our results showed that propofol could not only significantly inhibit tumor growth and glycolysis, but also ameliorate the pathological structure of CRC tumors. The current results proved that propofol could attenuate the malignant progression of CRC by preventing LDH activity, suggesting that propofol might be an effective therapeutic agent for CRC.

Pain Modulation from the Locus Coeruleus in a Model of Hydrocephalus: Searching for Oxidative Stress-Induced Noradrenergic Neuroprotection.

Pain transmission at the spinal cord is modulated by noradrenaline (NA)-mediated actions that arise from supraspinal areas. We studied the locus coeruleus (LC) to evaluate the expression of the cathecolamine-synthetizing enzyme tyrosine hydroxylase (TH) and search for local oxidative stress and possible consequences in descending pain modulation in a model of hydrocephalus, a disease characterized by enlargement of the cerebral ventricular system usually due to the obstruction of cerebrospinal fluid flow. Four weeks after kaolin injection into the cisterna magna, immunodetection of the catecholamine-synthetizing enzymes TH and dopamine-β-hydroxylase (DBH) was performed in the LC and spinal cord. Colocalization of the oxidative stress marker 8-OHdG (8-hydroxyguanosine; 8-OHdG), with TH in the LC was performed. Formalin was injected in the hindpaw both for behavioral nociceptive evaluation and the immunodetection of Fos expression in the spinal cord. Hydrocephalic rats presented with a higher expression of TH at the LC, of TH and DBH at the spinal dorsal horn along with decreased nociceptive behavioral responses in the second (inflammatory) phase of the formalin test, and formalin-evoked Fos expression at the spinal dorsal horn. The expression of 8-OHdG was increased in the LC neurons, with higher co-localization in TH-immunoreactive neurons. Collectively, the results indicate increased noradrenergic expression at the LC during hydrocephalus. The strong oxidative stress damage at the LC neurons may lead to local neuroprotective-mediated increases in NA levels. The increased expression of catecholamine-synthetizing enzymes along with the decreased nociception-induced neuronal activation of dorsal horn neurons and behavioral pain signs may indicate that hydrocephalus is associated with alterations in descending pain modulation.

Effects of exosomes from human adipose-derived mesenchymal stem cells on pulmonary vascular endothelial cells injury in septic mice and its mechanism

Effects of exosomes from human adipose-derived mesenchymal stem cells on pulmonary vascular endothelial cells injury in septic mice and its mechanism

Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats.

This study was planned to assess the potential protective effects of taxifolin against thioacetamide-induced hepatic encephalopathy and subsequently to portray its behavioural results. The experimental model was induced with three doses of (200mg/kg i.p.) thioacetamide and taxifolin (50 and 100mg/kg, p.o.) was administered for fourteen days. Taxifolin effectively attenuated hepatic encephalopathy through decrease in AST, ALT, ALP and LDH concentrations and improvement of hyperammonemia, and increase in antioxidant capacity by decreasing MDA, ROS, and increasing CAT and GSH. In addition, the expressions of NF-κB, TNF-α, IL-1β, caspase-3 and Bax was down-regulated while IL-10 and Bcl-2 expressions were up-regulated with taxifolin treatment. The recovery was confirmed by downregulation of iNOS and 8-OHdG expressions in our immunohistochemical analysis. Taxifolin treatment reduced the disrupting role of thioacetamide as seen by corrected hyperammonemia as well as preservation of astrocyte and hepatocyte structure. Elevated plus maze and locomotor activity tests also proved that taxifolin might repeal the neurobehavioral disabilities. In conclusion, taxifolin has shown hepatoprotective and neuroprotective roles with antioxidant and anti-inflammatory effects, as well as suppressing the excessive release of ammonia, and it eventually reversed neurobehavioral impairments.