Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation

Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

Resistance of LaCl_3 to Oxidative Stress Induced by 2, 4-Dichlorophenoxy

Cucumber seedlings were sprayed with different concentrations of LaCl_3 for 3 d continuously. After 7 d of this treatment, the plants were treated with 1200 mg·L^(-1) 2,4-dichlorophennoxy(2,4-D) for 24 h. The leaves were harvested and rinsed with 5 mmol·L^(-1) EDTA. The concentrations of photosynthetic pigments, soluble protein and metabolites related to oxidative stress and the activities of antioxidant enzymes in leaves were assayed. The results show that the treatment with appropriate concentration of LaCl_3 has resistant effect on oxidative stress induced by 2, 4-D. Proper concentration of LaCl_3 promotes the activity of antioxidant system in plants and alleviates the damage caused by 2, 4-D.

Research progress on the antioxidant therapy for gastric cancer

Gastric cancer is one of common malignant tumors from a global perspective, and its morbidity ranks the forth and also the second largest cause of cancer-related death worldwide. Many factors can cause gastric cancer, including helicobacter pylori infection, chronic inflammation, genetic factors et al. Among all of these, helicobacter pylori infection can significantly increase the production of reactive oxygen species（ROS） and reactive nitrogen species（RNS） in human stomach, which can cause the oxidative stress. Oxidative stress plays an important role in the pathogenesis of gastro-intestinal diseases such as mucosal damage, gastro-intestinal ulcers and cancer. Modern therapeutic treatments such as surgery and chemotherapy have undesired side effects, so the antioxidant therapy gains more and more attentions. Antioxidant therapy system comprises of various antioxidants（SOD, catalase, glutathione peroxidase and carnosine） and Chinese herbal medicine, which is mainly focused on the chemoprevention. Natural products and their derivatives, such as tea polyphenol, resveratrol and vitamins, have some potential benefits on their chemoprevention. Besides, much work has been done to understand the role of dietary factors playing in the prevention of gastrointestinal cancers. In this review based on some valuable studies, we aim to make some brief summaries about risk factors, pathogenic mechanism of oxidative stress and antioxidants therapy in gastric cancer.

Honokiol attenuates acetaminophen-induced acute liver injury by inhibiting hepatic CYP1A2 activity and improving liver mitochondrial dysfunction

Objective:Acetaminophen(APAP)overdose is a common cause of liver injury.This study aimed to investigate the protective effect of honokiol(Hon)against APAP-induced hepatotoxicity and its potential mechanism.Methods:C57BL/6 mice were administrated with Hon(10 and 30 mg/kg)after APAP(300 mg/kg)treatment.On 1.5 h and 5 h after Hon treatment,mice were sacrificed.Serum and liver were collected.And then,liver injury-related indexes,APAP metabolism-related indexes,mitochondrial respiratory chain function-related indexes,and mitochondrial membrane function-related protein expression were evaluated.Results:It was found that Hon significantly decreased serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST)activity and glutathione(GSH)depletion,increased hepatic catalase(CAT)and GSH peroxidase(GSH-Px)activities,reduced hepatic MDA and 3-nitrotyrosine contents,inhibited hepatic CYP1A2 activity and APAP protein adducts(APAP-CYS)formation.Meanwhile,oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased,whereas the release of H2O2 in the mitochondria was decreased following Hon treatment.Furthermore,Hon markedly down-regulated p-JNK in both cytosol and mitochondria,and obviously inhibited the release of apoptosis inducing factor(AIF)and endonuclease G(EndoG)from mitochondria to cytosol.Conclusion:Hon alleviated APAP-induced liver injury through the following pathways:Reducing the production of APAP-CYS by inhibiting CYP1A2 activity;Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT,GSH-Px and GSH;Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV;Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria,thereby reducing the release of AIF and EndoG.

Chlorpromazine protects against acetaminophen-induced liver injury in mice by modulating autophagy and c-Jun N-terminal kinase activation

Background and aim:Overdose of acetaminophen(APAP)leads to liver injury,which is one of the most common causes of liver failure in the United States.We previously demonstrated that pharmacological activation of autophagy protects against APAP-induced liver injury in mice via removal of damaged mitochondria and APAP-adducts(APAP-ADs).Using an image-based high-throughput screening for autophagy modulators,we recently identified that chlorpromazine(CPZ),a dopamine inhibitor used for anti-schizophrenia,is a potent autophagy inducer in vitro.Therefore,the aim of the present study is to determine whether CPZ may protect against APAP-induced liver injury via inducing autophagy.Methods:Wild type C57BL/6J mice were injected with APAP to induce liver injury.CPZ was administrated either at the same time with APAP(co-treatment)or 2 h later after APAP administration(post-treat-ment).Hemotoxyline and eosin(H&E)staining of liver histology,terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling(TUNEL)staining of necrotic cell death as well as serum levels of alanine aminotransferase(ALT)were used to monitor liver injury.Results:We found that CPZ markedly protected against APAP-induced liver injury as demonstrated by decreased serum levels of ALT,liver necrotic areas as well as TUNEL-positive cells in mice that were either co-treated or post-treated with CPZ.Mechanistically,we observed that CPZ increased the number of autolysosomes and decreased APAP-induced c-Jun N-terminal kinase activation without affecting the metabolic activation of APAP.Pharmacological inhibition of autophagy by chloroquine partially weak-ened the protective effects of CPZ against APAP-induced liver injury.Conclusions:Our results indicate that CPZ ameliorates APAP-induced liver injury partially via activating hepatic autophagy and inhibiting JNK activation.

Mitochondrial damage and biogenesis in acetaminophen-induced liver injury

Liver injury and acute liver failure caused by acetaminophen(APAP)overdose is the clinically most important drug toxicity in Western countries.Mechanistic investigations have revealed a central role of mitochondria in the pathophysiology.Excess formation of the reactive metabolite N-acetyl-p-benzoquinone imine(NAPQI)after an overdose leads to hepatic glutathione depletion,mitochondrial protein adducts formation and an initial oxidant stress,which triggers the activation of mitogen activated protein(MAP)kinase cascade ultimately leading to c-jun N-terminal kinase(JNK)phosphorylation.Phospho-JNK translocates to the mitochondria and amplifies the oxidative and nitrosative stress eventually causing the mitochondrial membrane permeability transition pore opening and cessation of adenosine triphosphate(ATP)synthesis.In addition,mitochondrial matrix swelling ruptures the outer membrane and releases endonucleases,which cause nuclear deoxyribonucleic acid(DNA)fragmentation.Together,the nuclear DNA damage and the extensive mitochondrial dysfunction result in necrotic cell death.However,the procell death signaling events are counteracted by adaptive responses such as autophagy and mitochondrial biogenesis.The improved mechanistic insight into the pathophysiology leads to better understanding of the mechanisms of action of the existing antidote N-acetylcysteine and justifies the clinical testing of novel therapeutics such as 4-methylpyrazole and calmangafodipir.