Atorvastatin Alleviates Behavioral Symptoms in MPTP-lesioned Mice: Associated With NOX2-mediated Autophagy and Oxidative Stress

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. It is characterized by static tremors, stiffness, slow movements, and gait disturbances, but it is also accompanied by anxiety and depression. Our previous study showed that statins, especially atorvastatin, could reduce the risk of PD, but the mechanism is still unclear. Results In this paper, we used an animal model of PD in which depression was determined by a tail suspension test, followed by an elevated plus-maze test to determine anxiety levels, and muscle status was measured by a rotarod test. We found that atorvastatin can increase muscle capacity and the coordination of movement and improved anxiety and depression，which mechanism may be related to decrease the expression of α-synuclein Ser129 and NADPH oxidase 2 (NOX2), and increase the protein expression of LC-3II/LC3-I, and promote autophagy flow. To further confirm that atorvastatin protection was achieved by inhibiting NOX2, we injected the midbrain substratum with NOX2 shRNA (M) lentivirus and found that silent NOX2 produced the same effect as atorvastatin. Further research found that atorvastatin could reduce MPTP-induced oxidative stress damage by increasing Nrf2, NQO-1 and HO-1, while inhibiting NOX2 decreased the antioxidative stress effect of atorvastatin. Conclusions： Our results suggest that atorvastatin can improve muscle capacity, anxiety and depression by inhibiting NOX2, which may be related to NOX2-mediated oxidative stress and autophagy in dopaminergic neurons. Atorvastatin may be identified as a drug that can effectively improve behavioral disorders in PD mice. NOX2 may be a potential gene target for new drug development in PD.

Download Full-text

Aspirin Eugenol Ester Protects Vascular Endothelium From Oxidative Injury by the Apoptosis Signal Regulating Kinase-1 Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2020.588755 ◽

2020 ◽

Vol 11 ◽

Author(s):

Mei-Zhou Huang ◽

Zhen-Dong Zhang ◽

Ya-Jun Yang ◽

Xi-Wang Liu ◽

Zhe Qin ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Endothelium ◽

Cell Apoptosis ◽

Oxidative Injury ◽

Vital Role ◽

Stress Effect ◽

Antioxidative Stress ◽

Aspirin Eugenol Ester

Aspirin eugenol ester (AEE) is a new potential pharmaceutical compound possessing anti-inflammatory, anti-cardiovascular disease, and antioxidative stress activity. The pharmacological activities of AEE are partly dependent on its regulation of cell apoptosis. However, it is still unclear how AEE inhibits cell apoptosis on the basis of its antioxidative stress effect. This study aimed to reveal the vascular antioxidative mechanism of AEE in response to H2O2-induced oxidative stress in HUVECs and paraquat-induced oxidative stress in rats. In the different intervention groups of HUVECs and rats, the expression of ASK1, ERK1/2, SAPK/JNK, and p38 and the phosphorylation levels of ERK1/2, SAPK/JNK, and p38 were measured. The effects of ASK1 and ERK1/2 on the anti-apoptotic activity of AEE in the oxidative stress model were probed using the corresponding inhibitors ASK1 and ERK1/2. The results showed that in the HUVECs, 200 μM H2O2 treatment significantly increased the phosphorylation of SAPK/JNK and the level of ASK1 but decreased the phosphorylation of ERK1/2, while in the HUVECs pretreated with AEE, the H2O2-induced changes were significantly ameliorated. The findings were observed in vitro and in vivo. Moreover, inhibition of ASK1 and ERK1/2 showed that ASK1 plays a vital role in the protective effect of AEE on H2O2-induced apoptosis. All findings suggested that AEE protects the vascular endothelium from oxidative injury by mediating the ASK1 pathway.

Download Full-text

Effects of electrotactic exercise and antioxidant EUK-134 on oxidative stress relief in Caenorhabditis elegans

PLoS ONE ◽

10.1371/journal.pone.0245474 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245474

Author(s):

Thi Thanh Huong Pham ◽

Wan-Ying Huang ◽

Chang-Shi Chen ◽

Wen-Tai Chiu ◽

Han-Sheng Chuang

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Intracellular Signaling ◽

Stress Effect ◽

Wild Type ◽

Antioxidant Supplementation ◽

Antioxidative Stress ◽

Biochemical Indices ◽

And Oxidative Stress

Antioxidant uptake and regular exercise are two well-acknowledged measures used for rejuvenation and oxidative stress elimination. Previous studies have revealed that moderate exercise mildly increases intracellular signaling oxidant levels and strengthens the ability of an organism to deal with escalating oxidative stress by upregulating antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase. Antioxidant supplementation directly scavenges intracellular reactive oxygen species (ROS) to reduce oxidative stress. However, research to understand the impacts of these enzymes on mitigating oxidative stress from the perspective of simple animals is limited. Herein, we show that exercise combined with antioxidant supplementation ameliorates the physiological phenotypes and markers of aging in wild-type and SOD/CAT-deficient Caenorhabditis elegans. We discovered that treated wild-type and gene-deficient worms show better survivorship, reproduction, and motility compared with their control counterparts. Assays of biochemical indices revealed that variations in sod-3 expression under different stress levels imply an inducible enzyme response resulting from exercise training and antioxidant supplementation. In addition, induced ROS resistance obtained from any type of treatment could persist for several days even after treatment cessation, thus suggesting a potential long-term antioxidative stress effect. Our findings confirm that exercise, antioxidant supplementation, and their combination could significantly improve the ability of C. elegans to withstand adverse stress. Our observations provide promising insights into future therapies of anti-oxidative stress in higher animals.

Download Full-text

The Inhibition Effect of the Seaweed Polyphenol, 7-Phloro-Eckol from Ecklonia Cava on Alcohol-Induced Oxidative Stress in HepG2/CYP2E1 Cells

Marine Drugs ◽

10.3390/md19030158 ◽

2021 ◽

Vol 19 (3) ◽

pp. 158

Author(s):

Liyuan Lin ◽

Shengtao Yang ◽

Zhenbang Xiao ◽

Pengzhi Hong ◽

Shengli Sun ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Liver Disease ◽

B Cell Lymphoma ◽

Nuclear Factor Κb ◽

Ecklonia Cava ◽

Stress Effect ◽

Stress Injury ◽

Antioxidative Stress ◽

Apoptosis Proteins

The liver is vulnerable to oxidative stress-induced damage, which leads to many diseases, including alcoholic liver disease (ALD). Liver disease endanger people’s health, and the incidence of ALD is increasing; therefore, prevention is very important. 7-phloro-eckol (7PE) is a seaweed polyphenol, which was isolated from Ecklonia cava in a previous study. In this study, the antioxidative stress effect of 7PE on HepG2/CYP2E1 cells was evaluated by alcohol-induced cytotoxicity, DNA damage, and expression of related inflammation and apoptosis proteins. The results showed that 7PE caused alcohol-induced cytotoxicity to abate, reduced the amount of reactive oxygen species (ROS) and nitric oxide (NO), and effectively inhibited DNA damage in HepG2/CYP2E1 cells. Additionally, the expression levels of glutathione (GSH), superoxide dismutase (SOD), B cell lymphoma 2 (Bcl-2), and Akt increased, while γ-glutamyltransferase (GGT), Bcl-2 related x (Bax), cleaved caspase-3, cleaved caspase-9, nuclear factor-κB (NF-κB), and JNK decreased. Finally, molecular docking proved that 7PE could bind to BCL-2 and GSH protein. These results indicate that 7PE can alleviate the alcohol-induced oxidative stress injury of HepG2 cells and that 7PE may have a potential application prospect in the future development of antioxidants.

Download Full-text

Ultrastructural Changes in Hepatocytes and Chemopreventive Effects of Short-Term Administration of Curcuma longa L. against Oxidative Stress-Induced Toxicity: Improvement Mechanisms of Liver Detoxification

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9535731 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Mohammed A. Hasan

Keyword(s):

Oxidative Stress ◽

Day Treatment ◽

Curcuma Longa ◽

Negative Control ◽

Ultrastructural Changes ◽

Enzyme Analysis ◽

Control Group ◽

Stress Effect ◽

Sprague Dawley ◽

Antioxidative Stress

The rhizomes of Curcuma longa L. (CL) have been widely used in herbal medicines worldwide. It has been shown to possess prophylactic effects against oxidative stress. However, there is a paucity of information regarding the protective role of CL against oxidative stress in the absence of toxic agents. The aim of the study was to elucidate the antioxidative stress pharmacodynamics of CL. Eighteen 12-week-old Sprague-Dawley rats weighing about 300 ± 25 gm were divided equally into six groups. Four of the groups were supplemented with CL at 100 mg/kg b.w./day orally (P.O.) and labeled as 1st, 3rd, 5th, and 6th day groups. The PCx (positive control) group was given distilled water orally, and the NCx (negative control) group rats were provided with food and water ad libitum. Blood samples were collected, and rats were sacrificed on days 1, 3, 5, and 6 (2 h) posttreatment. The blood was used for oxidative stress enzyme analysis (SOD, GSH-Px, and MDA) and liver (ALT) and kidney (creatinine) function assay, and the liver was dissected for histology. The results revealed that CL exhibited an antioxidative stress effect in the liver and kidneys as indicated by the low levels of ALT and creatinine. In response to antioxidant enzymes, especially that of the 3rd-day treatment group, an increase in SOD and GSH-Px indirectly caused an alleviation of oxidative stress, leading to a much lower level of MDA. It was concluded that treatment with CL at 100 mg/kg b.w./per day for three consecutive days demonstrated the highest efficacy in abating oxidative stress in rats.

Download Full-text

Physical exercise protects dynamic balance and motor coordination of rats treated with vincristine

Revista Brasileira de Fisiologia do Exercício ◽

10.33233/rbfex.v19i5.4220 ◽

2020 ◽

Vol 19 (5) ◽

pp. 336

Author(s):

Luiza Minato Sagrillo ◽

Viviane Nogueira De Zorzi ◽

Luiz Fernando Freire Royes ◽

Michele Rechia Fighera ◽

Beatriz Da Silva Rosa Bonadiman ◽

...

Keyword(s):

Oxidative Stress ◽

Locomotor Activity ◽

Physical Exercise ◽

Motor Coordination ◽

Dynamic Balance ◽

Exercise Group ◽

Adult Rats ◽

The Central Nervous System ◽

Stress Damage ◽

Training Protocol

Physical exercise has been shown to be an important modulator of the antioxidant system and neuroprotective in several diseases and treatments that affect the central nervous system. In this sense, the present study aimed to evaluate the effect of physical exercise in dynamic balance, motor coordination, exploratory locomotor activity and in the oxidative and immunological balance of rats treated with vincristine (VCR). For that, 40 adult rats were divided into two groups: exercise group (6 weeks of swimming, 1h/day, 5 days/week, with overload of 5% of body weight) and sedentary group. After training, rats were treated with 0.5 mg/kg of vincristine sulfate for two weeks or with the same dose of 0.9% NaCl. The behavioral tests were conducted 1 and 7 days after each dose of VCR. On day 15 we carried out the biochemical analyzes of the cerebellum. The physical exercise was able to protect against the loss of dynamic balance and motor coordination and, had effect per se in the exploratory locomotor activity, and neutralize oxidative stress, damage DNA and immune damage caused by VCR up to 15 days after the end of the training protocol. In conclusion, we observed that previous physical training protects of the damage motor induced by vincristine.Key-words: exercise, oxidative stress, neuroprotection, cerebellum.

Download Full-text

Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

Current Bioactive Compounds ◽

10.2174/1573407216666200203142722 ◽

2020 ◽

Vol 16 (9) ◽

pp. 1319-1327

Author(s):

Ferdous Khan ◽

Syed A. Kuddus ◽

Md. H. Shohag ◽

Hasan M. Reza ◽

Murad Hossain

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Reduced Glutathione ◽

Forced Swim Test ◽

Tail Suspension Test ◽

Glutathione Depletion ◽

Swim Test ◽

Stress Markers ◽

Immobility Time ◽

Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

Download Full-text

Idebenone Treatment Mediates the Effect of Menadione Oxidative Stress Damage in Saccharomyces cerevisiae

Drug Metabolism Letters ◽

10.2174/1872312811206020120 ◽

2012 ◽

Vol 6 (2) ◽

pp. 120-123 ◽

Cited By ~ 2

Author(s):

Oliver Gamondi ◽

Sebastian Chapela ◽

Ines Nievas ◽

Isabel Burgos ◽

Manuel Alonso ◽

...

Keyword(s):

Oxidative Stress ◽

Saccharomyces Cerevisiae ◽

Stress Damage

Download Full-text

Evidence for Oxidative Stress Damage Following High Intensity Anaerobic Performance

The Open Sports Medicine Journal ◽

10.2174/1874387000802010009 ◽

2008 ◽

Vol 2 (1) ◽

pp. 9-13 ◽

Cited By ~ 1

Author(s):

Julien S. Baker ◽

Bruce Davies

Keyword(s):

Oxidative Stress ◽

High Intensity ◽

Anaerobic Performance ◽

Stress Damage

Download Full-text

The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

The Natural Products Journal ◽

10.2174/2210315509666190723131511 ◽

2020 ◽

Vol 10 (5) ◽

pp. 578-586

Author(s):

Areeg M. Abdelrazek ◽

Shimaa A. Haredy

Keyword(s):

Oxidative Stress ◽

Coenzyme Q10 ◽

Protective Role ◽

Albino Rats ◽

Distilled Water ◽

Negative Effects ◽

Adult Rats ◽

Stress Damage ◽

The Impact ◽

Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

Download Full-text