scholarly journals Maternal Swimming Exercise During Pregnancy Improves Memory Through Enhancing Neurogenesis and Suppressing Apoptosis via Wnt/β-Catenin Pathway in Autistic Mice

2021 ◽  
Vol 25 (Suppl 2) ◽  
pp. S63-71
Author(s):  
Sang-Seo Park ◽  
Chang-Ju Kim ◽  
Seong-Hyun Kim ◽  
Tae-Woon Kim ◽  
Sam-Jun Lee
Keyword(s):  
Valproic Acid ◽  
Caspase 3 ◽  
Memory Function ◽  
B Cell Lymphoma ◽  
Exercise Group ◽  
Swimming Exercise ◽  
Avoidance Task ◽  
Morris Water Maze Task ◽  
Pregnant Mice ◽  
Exercise During Pregnancy

Purpose: Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway.Methods: On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2’-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out.Results: Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups.Conclusions: Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.

Electroacupuncture ameliorates CUMS-induced depression-like behavior: involvement of the glutamatergic system and apoptosis in rats

2020 ◽  
Vol 23 ◽  
Author(s):  
Qin Guo ◽  
Xian-Ming Lin ◽  
Zhong Di ◽  
Quan-Ai Zhang ◽  
Shuo Jiang
Keyword(s):  
Nmda Receptor ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Sucrose Preference ◽  
Expression Level ◽  
Receptor Subunit ◽  
Glutamatergic System ◽  
Ionotropic Receptor ◽  
Nmda Receptor Subunit ◽  
Expression Levels

Background: Converging evidence indicates that glutamatergic system and glia are directly implicated in the pathophysiology of depression. Clinical studies indicate that electroacupuncture (EA) has antidepressant-like effect with low side effects for depression. However, the underlying antidepressant mechanism of acupuncture remains obscure. Methods: Chronic unpredictable mild stress (CUMS)-induced depressive rats were used to induce depressive-like behavior, and evaluated by the weight change, open field test, sucrose preference test, and novelty suppressed feeding test. EA, NMDA receptor subunit 2A antagonist (NR2A RA) or NMDA receptor subunit 2B antagonist (NR2B RA) was used for comparison. High performance liquid chromatography (HPLC) was performed to detect the content of hippocampal glutamate, while western blot for the hippocampal protein expression levels of calcium/calmodulin-dependent protein kinase II (CaMKII), Bax, caspase 3 and B-cell lymphoma-2 (Bcl-2). The distribution of glutamate ionotropic receptor NMDA type subunit 2A (NR2A), neuronal nuclear protein (NeuN), glutamate ionotropic receptor NMDA type subunit 2B (NR2B) and glial fibrillary acidic protein (GFAP) were detected by immunofluorescence. Results: Significant depression behavior (reduced body weight and sucrose preference, increased feeding and immobility time) was produced in CUMS-induced depressive rats, which was reversed significantly by EA. EA decreased hippocampal glutamate level. EA led to a significant decrease in expression levels of Bax, caspase 3 and CaMKⅡ accompanied by increased Bcl-2 expression level. Furthermore, EA significantly increased NR2A expression level as well as decreased NR2B expression level in hippocampus. Conclusion: EA ameliorated depression-like behavior in CUMS rats, which might be mediated, at least in part, by regulating the glutamate, NMDA receptors and apoptosis in the hippocampus.

Anticancer Activity of Platinum (II) Complex with 2-Benzoylpyridine by Induction of DNA Damage, S-Phase Arrest, and Apoptosis

2020 ◽  
Vol 20 (4) ◽  
pp. 504-517
Author(s):  
Yu-Lan Li ◽  
Xin-Li Gan ◽  
Rong-Ping Zhu ◽  
Xuehong Wang ◽  
Duan-Fang Liao ◽  
...  
Keyword(s):  
Dna Damage ◽  
B Cell ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
S Phase ◽  
Caspase 9

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

scholarly journals Oxidative Stress and Apoptotic Responses Elicited by Nostoc-Synthesized Silver Nanoparticles against Different Cancer Cell Lines

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2099 ◽  
Author(s):  
Reham Samir Hamida ◽  
Gadah Albasher ◽  
Mashael Mohammed Bin-Meferij
Keyword(s):  
Oxidative Stress ◽  
Silver Nanoparticles ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Mammalian Target Of Rapamycin ◽  
B Cell Lymphoma ◽  
Phosphorylated Akt ◽  
Hct 116 ◽  
Mcf 7

Green nanoparticles represent a revolution in bionanotechnology, providing opportunities to fight life-threatening diseases, such as cancer, with less risk to the environment and to human health. Here, for the first time, we systematically investigated the anticancer activity and possible mechanism of novel silver nanoparticles (N-SNPs) synthesized by Nostoc Bahar M against the MCF-7 breast cancer cells, HCT-116 colorectal adenocarcinoma cells, and HepG2 liver cancer cells, using cell viability assays, morphological characterization with inverted light and transmission electron microscopy, antioxidants and enzymes (glutathione peroxidase (GPx), glutathione (GSH), adenosine triphosphatase (ATPase), and lactate dehydrogenase (LDH)), and western blotting (protein kinase B (Akt), phosphorylated-Akt (p-Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2), tumor suppressor (p53), and caspase 3). N-SNPs decreased the viability of MCF-7, HCT-116, and HepG2 cells, with half-maximal inhibitory concentrations of 54, 56, and 80 µg/mL, respectively. They also significantly increased LDH leakage, enhanced oxidative stress via effects on antioxidative markers, and caused metabolic stress by significantly decreasing ATPase levels. N-SNPs caused extensive ultrastructural alterations in cell and nuclear structures, as well as in various organelles. Furthermore, N-SNPs triggered apoptosis via the activation of caspase 3 and p53, and suppressed the mTOR signaling pathway via downregulating apoptosis-evading proteins in MCF-7, HCT-116, and HepG2 cells. Ultrastructural analysis, together with biochemical and molecular analyses, revealed that N-SNPs enhanced apoptosis via the induction of oxidative stress and/or through direct interactions with cellular structures in all tested cells. The cytotoxicity of Nostoc-mediated SNPs represents a new strategy for cancer treatment via targeting various cell death pathways. However, the potential of N-SNPs to be usable and biocompatible anticancer drug will depend on their toxicity against normal cells.

Protective efficacy of carnosic acid against hydrogen peroxide induced oxidative injury in HepG2 cells through the SIRT1 pathway

2015 ◽  
Vol 93 (8) ◽  
pp. 625-631 ◽  
Author(s):  
Yan Hu ◽  
Ning Zhang ◽  
Qing Fan ◽  
Musen Lin ◽  
Ce Zhang ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Hepg2 Cells ◽  
Manganese Superoxide Dismutase ◽  
Caspase 3 ◽  
Protective Efficacy ◽  
B Cell Lymphoma ◽  
Sirtuin 1 ◽  
Carnosic Acid ◽  
Protective Effects ◽  
Hepatocyte Damage

Carnosic acid (CA), found in rosemary, has been reported to have antioxidant and antiadipogenic properties. Here, we investigate the molecular mechanism by which CA inhibits hydrogen peroxide (H2O2)-induced injury in HepG2 cells. Cells were pretreated with 2.5–10 μmol/L CA for 2 h and then exposed to 3 mmol/L H2O2 for an additional 4 h. CA dose-dependently increased cell viability and decreased lactate dehydrogenase activities. Pretreatment with CA completely attenuated the inhibited expression of manganese superoxide dismutase (MnSOD) and the B-cell lymphoma-extra large (Bcl-xL), and reduced glutathione activity caused by H2O2, whereas it reversed reactive oxygen species accumulation and the increase in cleaved caspase-3. Importantly, sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, was significantly increased by CA. Considering the above results, we hypothesized that SIRT1 may play important roles in the protective effects of CA in injury induced by H2O2. As expected, SIRT1 suppression by Ex527 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) and siRNA-mediated SIRT1 silencing (si-SIRT1) significantly aggravated the H2O2-induced increased level of cleaved caspase-3 but greatly reduced the decreased expression of MnSOD and Bcl-xL. Furthermore, the positive regulatory effect of CA was inhibited by si-SIRT1. Collectively, the present study indicated that CA can alleviate H2O2-induced hepatocyte damage through the SIRT1 pathway.

Protective Effects of Crataegus pinnatifida Extracts and Crataegolic Acid Against Neurotoxicity of Paraquat in PC12 Cells

2021 ◽  
Vol 20 (1) ◽  
pp. 76-83
Author(s):  
Chi-Sen Chang ◽  
Yuh-Chiang Shen ◽  
Chi-Wen Juan ◽  
Chia-Lin Chang ◽  
Po-Kai Lin
Keyword(s):  
Reactive Oxygen Species ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Active Component ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
B Cell Lymphoma ◽  
Oxygen Species ◽  
Protein Levels ◽  
Crataegus Pinnatifida

The neuroprotective mechanisms of Crataegus pinnatifida extracts and crataegolic acid were studied using paraquat induced cytotoxicity in PC12 cells. C. pinnatifida extracts were prepared using hexane, ethyl acetate, and 95% ethanol. Additionally, crataegolic acid (also known as maslinic acid) was found in C. pinnatifida extracts. Assessment methods included the examinations of cytotoxicity, intracellular reactive oxygen species and calcium changes, activity of caspase-3 and α-synuclein, apoptotic cell death, and the expression levels of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins to investigate the neuroprotective mechanisms of C. pinnatifida extracts and its active component, crataegolic acid. The three extracts and crataegolic acid exhibited potent neuroprotective actions against paraquat induced PC12 cell apoptosis at 5–20µg/mL and 80–100µM concentrations, respectively. The key protective mechanisms included decreasing cell apoptosis, upregulating Bcl-2 protein levels, and downregulating Bax protein levels. The 95% ethanol extract also decreased paraquat induced reactive oxygen species production, calcium overloading, and caspase-3 and α-synuclein activities. The beneficial effects of these extracts could be explained by the active component, crataegolic acid that also inhibited paraquat-induced apoptosis through the suppression of reactive oxygen species generation and the caspase-3 signaling pathway.

scholarly journals The Role of Caspase-3, Apoptosis-Inducing Factor, and B-cell Lymphoma-2 Expressions in Term Premature Rupture of Membrane

2018 ◽  
Vol 40 (12) ◽  
pp. 733-739
Author(s):  
Ketut Negara ◽  
Ketut Suwiyoga ◽  
Tjokorda Pemayun ◽  
Anak Agung Sudewi ◽  
Nyoman Astawa ◽  
...  
Keyword(s):  
B Cell ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Term Pregnancy ◽  
Premature Rupture ◽  
Term Delivery ◽  
Chi Squared ◽  
Apoptosis Inducing Factor

Objective To determine the role of caspase-3, apoptosis-inducing factor (AIF), and B-cell lymphoma-2 (Bcl-2) expressions in term premature rupture of membrane (PROM). Methods An analytic observational study with case-control design was conducted, involving 52 subjects (37–42 weeks of gestation) who were divided into 2 groups: 26 cases of term delivery with PROM, and 26 controls of term delivery without PROM. The expressions of caspase-3, AIF, and Bcl-2 in the amniotic membrane were determined by immunohistochemistry. Data were analyzed using the chi-squared test. The risk of PROM was expressed by odds ratio (OR). Results There were no significant differences in age, parity and body mass index between the two groups (p > 0.05). High caspase-3 and AIF expressions increased the risk of PROM 17.64 times (OR = 17.64; 95% CI = 4.44–70.07; p = 0.001) and 9.45 times (OR = 9.45; 95% CI= 2.62–34.07; p = 0.001), respectively, while low Bcl-2 expression increased 10.39 times (OR = 10.39; 95% CI = 2.73–39.56; p = 0.001)the risk of PROM . Conclusion High caspase-3 and AIF expressions and low Bcl-2 expression were risk factors for term PROM. Caspase-dependent and independent pathways of apoptosis were involved in the mechanism of PROM in term pregnancy.

scholarly journals Evidence from human placenta, ER-stressed trophoblasts and transgenic mice links transthyretin proteinopathy to preeclampsia

2022 ◽  
Author(s):  
Shibin Cheng ◽  
Zheping Huang ◽  
Sayani Banerjee ◽  
Joel Buxbaum ◽  
Surendra Sharma
Keyword(s):  
Transgenic Mice ◽  
Intrauterine Growth Restriction ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Wild Type ◽  
Junctional Zone ◽  
Intrauterine Growth ◽  
Pregnant Mice ◽  
Umbilical Arteries ◽  
Trophoblast Cell Line

We have demonstrated that protein aggregation plays a pivotal role in the pathophysiology of preeclampsia (PE) and identified several aggregated proteins in the circulation of PE patients, most significantly the serum protein transthyretin (TTR). Here we show robust accumulation of TTR aggregates in the placentas of women with early-onset PE (e-PE). TTR aggregation was inducible in primary human trophoblasts (PHTs) and the TCL-1 trophoblast cell line by ER stress inducers or autophagy-lysosomal disruptors. Hypoxia/reoxygenation (H/R) of cultured PHTs increased intracellular BiP, phosphorylated IRE1alpha, PDI and Ero-1, all markers of the UPR, and the apoptosis mediator caspase-3. Blockade of IRE1alpha inhibited H/R-induced upregulation of Ero-1 in PHTs. Excessive UPR was observed in the PE placenta. Further, pregnant mice, overexpressing transgene encoded wild type human TTR, displayed aggregated TTR in the junctional zone of the placenta and PE-like features including hypertension, proteinuria, intrauterine growth restriction, kidney injury, and elevated levels of the PE biomarkers serum sFlt-1 and endoglin. High Resolution Ultrasound analysis revealed low blood flow in uterine and umbilical arteries compared to that found in wild type pregnant mice. On the other hand, loss of mouse TTR function did not cause any pregnancy abnormalities in Ttr-/- mice. These observations in the PE placenta, cultured trophoblast cells and TTR transgenic mice indicate that TTR aggregation is an important causal contributor to PE pathophysiology.

scholarly journals Perfluorooctanoic Acid Exposure in Early Pregnancy Induces Oxidative Stress in The Uterus and Liver in Mice

2021 ◽  
Author(s):  
Yan Zhang ◽  
Linchao Zhang ◽  
JiaLu Bao ◽  
LianTao Liu ◽  
Xiaodan Wang
Keyword(s):  
Early Pregnancy ◽  
Caspase 3 ◽  
Liver Toxicity ◽  
Liver Weight ◽  
Perfluorooctanoic Acid ◽  
Control Group ◽  
Dependent Manner ◽  
Subsequent Increase ◽  
Decidual Cells ◽  
Pregnant Mice

Abstract To investigate the mechanism perfluorooctanoic acid (PFOA)’s toxicity on the uterus and liver of the mice during early pregnancy, pregnant mice were given 0, 1, 5, 10, 20, 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7, and sacrificed on GD 9. Uterus and liver weight were recorded, liver and uterine indexes were calculated, histopathological changes of the liver and uterus were examined, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in liver were detected by spectrophotometric method. Expression of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells were detected by immunohistochemistry and the TUNEL method was used to detect apoptotic uterine cells. Results showed that liver weight increased, and the uterus index was significantly reduced at 40 mg/kg compared with the control group. With increasing doses of PFOA, levels of SOD and GSH-PX were significantly decreased, and MDA significantly increased in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused greater harm to the uterus and congestion and resorption may occur. Expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was down-regulated, which decreased the ratio of Bcl-2/Bax. It is therefore proposed that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may induce embryo loss or damage.

scholarly journals Short-Chain Fatty Acids Alleviate Hepatocyte Apoptosis Induced by Gut-Derived Protein-Bound Uremic Toxins

2021 ◽  
Vol 8 ◽  
Author(s):  
Mingjuan Deng ◽  
Xingqi Li ◽  
Weiwei Li ◽  
Jiahui Gong ◽  
Xiaoying Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Short Chain Fatty Acids ◽  
Uremic Toxins ◽  
Short Chain ◽  
Liver Carcinoma ◽  
Apoptosis Protein ◽  
Induced Apoptosis ◽  
Chain Fatty Acids

Chronic kidney disease (CKD) is characterized with the influx of uremic toxins, which impairs the gut microbiome by decreasing beneficial bacteria that produce short-chain fatty acids (SCFAs) and increasing harmful bacteria that produce gut-derived protein-bound uremic toxins (PBUTs). This study aimed to assess the proapoptotic effects of three major gut-derived PBUTs in hepatocytes, and the effects of SCFAs on apoptosis phenotype in vitro. HepG2 (human liver carcinoma cells) and THLE-2 (immortalized human normal liver cells) cell line were incubated with 0, 2, 20, 200, 2000 μM p-cresol sulfate (PCS), indoxyl sulfate (IS), and hippuric acid (HA), respectively, for 24 h. Flow cytometry analysis indicated that three uremic toxins induced varying degrees of apoptosis in hepatocytes and HA represented the highest efficacy. These phenotypes were further confirmed by western blot of apoptosis protein expression [Caspase-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax)]. Human normal hepatocytes (THLE-2) are more sensitive to PBUTs-induced apoptosis compared with human hepatoma cells (HepG2). Mechanistically, extracellular HA could enter hepatocytes, increase reactive oxygen species (ROS) generation, and decrease mitochondrial membrane potential dose-dependently in THLE-2 cells. Notably, coculture with SCFAs (acetate, propionate, butyrate) for 24 h significantly improved HA-induced apoptosis in THLE-2 cells, and propionate (500 μM) represented the highest efficacy. Propionate reduction of apoptosis was associated with improving mitochondria dysfunction and oxidative stress in a manner involving reducing Caspase-3 expression, ROS production, and increasing the Bcl-2/Bax level. As such, our studies validated PBUTs accumulation might be an important cause of liver dysfunction in patients with CKD, and supplementation of SCFAs might be a viable way to protect the liver for patients with CKD.

scholarly journals Oxymatrine Ameliorates Memory Impairment in Diabetic Rats by Regulating Oxidative Stress and Apoptosis: Involvement of NOX2/NOX4

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yongpan Huang ◽  
Xinliang Li ◽  
Xi Zhang ◽  
Jiayu Tang
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Brain Injury ◽  
Western Blotting ◽  
Caspase 3 ◽  
Memory Function ◽  
Diabetic Rats ◽  
Oxygen Species ◽  
Expression Levels

Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait and has been shown to exhibit a diverse range of pharmacological properties. The aim of the present study was to investigate the role of OMT in diabetic brain injury in vivo and in vitro. Diabetic rats were induced by intraperitoneal injection of a single dose of 65 mg/kg streptozotocin (STZ) and fed a high-fat and high-cholesterol diet. Memory function was assessed using a Morris water maze test. A SH-SY5Y cell injury model was induced by incubation with glucose (30 mM/l) to simulate damage in vitro. The serum fasting blood glucose, insulin, serum S100B, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were analyzed using commercial kits. Morphological changes were observed using Nissl staining and electron microscopy. Cell apoptosis was assessed using Hoechst staining and TUNEL staining. NADPH oxidase (NOX) and caspase-3 activities were determined. The effects of NOX2 and NOX4 knockdown were assessed using small interfering RNA. The expression levels of NOX1, NOX2, and NOX4 were detected using reverse transcription-quantitative PCR and western blotting, and the levels of caspase-3 were detected using western blotting. The diabetic rats exhibited significantly increased plasma glucose, insulin, reactive oxygen species (ROS), S-100B, and MDA levels and decreased SOD levels. Memory function was determined by assessing the percentage of time spent in the target quadrant, the number of times the platform was crossed, escape latency, and mean path length and was found to be significantly reduced in the diabetic rats. Hyperglycemia resulted in notable brain injury, including histological changes and apoptosis in the cortex and hippocampus. The expression levels of NOX2 and NOX4 were significantly upregulated at the protein and mRNA levels, and NOX1 expression was not altered in the diabetic rats. NOX and caspase-3 activities were increased, and caspase-3 expression was upregulated in the brain tissue of diabetic rats. OMT treatment dose-dependently reversed behavioral, biochemical, and molecular changes in the diabetic rats. In vitro, high glucose resulted in increases in reactive oxygen species (ROS), MDA levels, apoptosis, and the expressions of NOX2, NOX4, and caspase-3. siRNA-mediated knockdown of NOX2 and NOX4 decreased NOX2 and NOX4 expression levels, respectively, and reduced ROS levels and apoptosis. The results of the present study suggest that OMT alleviates diabetes-associated cognitive decline, oxidative stress, and apoptosis via NOX2 and NOX4 inhibition.

Sign in / Sign up

Export Citation Format

Share Document