IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

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CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

Experimental Biology and Medicine ◽

10.1177/15353702211047183 ◽

2021 ◽

pp. 153537022110471

Author(s):

Junxia Zhang ◽

Xue Lin ◽

Jinxiu Xu ◽

Feng Tang ◽

Lupin Tan

Keyword(s):

Oxidative Stress ◽

Uric Acid ◽

Inflammatory Responses ◽

Umbilical Vein ◽

Specific Inhibitor ◽

Endothelial Damage ◽

Endothelial Injury ◽

Sprague Dawley ◽

Protein Levels ◽

And Oxidative Stress

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

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Lipopolysaccharide induces neuroglia activation and NF-κB activation in cerebral cortex of adult mice

Laboratory Animal Research ◽

10.1186/s42826-019-0018-9 ◽

2019 ◽

Vol 35 (1) ◽

Cited By ~ 4

Author(s):

Ju-Bin Kang ◽

Dong-Ju Park ◽

Murad-Ali Shah ◽

Myeong-Ok Kim ◽

Phil-Ok Koh

Keyword(s):

Oxidative Stress ◽

Cerebral Cortex ◽

Calcium Binding ◽

Inflammatory Responses ◽

Inflammatory Factors ◽

Adult Mice ◽

Tnf Α ◽

Factor Α ◽

And Oxidative Stress ◽

Necrosis Factor

Abstract Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 μg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.

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Benefit Agmatine Effects in Experimental Multiple Sclerosis. CNS Nitrosative and Oxidative Stress Suppression / Protektivni Efekti Agmatina U Eksperimentalnoj Multiploj Sklerozi. Supresija Nitrozativnog I Oksidativnog Stresa U CNS-U

Acta Facultatis Medicae Naissensis ◽

10.2478/afmnai-2014-0029 ◽

2014 ◽

Vol 31 (4) ◽

pp. 233-243

Author(s):

Ivana Stojanović ◽

Srđan Ljubisavljević ◽

Ivana Stevanović ◽

Slavica Stojnev ◽

Radmila Pavlović ◽

...

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Clinical Symptoms ◽

Protective Effects ◽

Sprague Dawley ◽

Autoimmune Encephalomyelitis ◽

Sod Activity ◽

Neuroprotective Effects ◽

Sprague Dawley Rats ◽

And Oxidative Stress

Summary The aim of this study was to investigate the exogenous agmatine influence on nitrosative and oxidative stress parameters in acute phase of multiple sclerosis (MS) experimental model, experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous injection of myelin basic protein (50 μg per animal). Sprague-Dawley rats were divided into five groups: I group - (CG), treated by PBS (i.p.), II group - (EAE), III group - (CFA), treated with Complete Freund’s adjuvant (0.2 ml subcutaneously), IV group - (EAE+AGM), treated by agmatine (75 mg/kg bw i.p.) upon EAE induction and V group - (AGM), received only agmatine in the same dose. The animals were treated every day during experiment - from day 0 to 15, and clinically scored every day. They were sacrificed on day 16 from MBP application. NO2+NO3, S-nitrosothiols (RSNO), malondyaldehide (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were determined in rat whole encephalitic mass (WEM) and cerebellum homogenates. Agmatine exerted strong protective effects on EAE clinical symptoms (p<0.05). In EAE brain homogenates, NO2+NO3, RSNO and MDA concentrations were increased compared to CG values. Agmatine treatment diminished NO2+NO3, RSNO and MDA levels in EAE animals (p<0.05). In EAE rats, GSH level and SOD activity were decreased compared to CG values, but agmatine treatment increased both parameters compared to EAE untreated animals (p<0.05). Immunohistochemical staining supported the clinical and biochemical findings in all groups. The CNS changes in EAE are successfully supressed by agmatine application, which could be the the new aspect of the neuroprotective effects of agmatine.

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The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

10.21203/rs.2.16758/v1 ◽

2019 ◽

Author(s):

Jie Guo ◽

Xiaolu Cao ◽

Xianmin Hu ◽

Shulan Li ◽

Jun Wang

Keyword(s):

Oxidative Stress ◽

Terminal Deoxynucleotidyl Transferase ◽

Control Group ◽

Tunel Staining ◽

High Dose ◽

Sprague Dawley ◽

Curcumin Treatment ◽

Concurrent Administration ◽

Tnf Α ◽

Anti Inflammatory

Abstract Background: As a chemical extensively used in industrial areas as well as formed during heating of carbohydrate-rich food and tobacco, acrylamide (ACR) has been known as well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats. Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cerebral homogenates were detected using ELISA assay. Results: Concurrent administration of curcumin at the oral doses of 50 and 100 mg/kg with ACR significantly protected the rats from ACR-induced weigh loss and motor function deficits, and improved the pathological alterations in the ACR-intoxicated brains. Curcumin treatment especially at a high dose enhanced the TERT mRNA expression level and increased the number of TERT-positive nerve cells in cortex tissues of ACR intoxicated rats. The levels of MDA, TNF-α and IL-1β in the cerebral homogenates were reduced, the contents of GSH as well as the activities of SOD and GSH-Px were increased by curcumin treatment, compared to ACR control group. Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. And maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

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Role of the angiotensin II AT2 receptor in inflammation and oxidative stress: opposing effects in lean and obese Zucker rats

AJP Renal Physiology ◽

10.1152/ajprenal.00616.2010 ◽

2011 ◽

Vol 300 (3) ◽

pp. F700-F706 ◽

Cited By ~ 47

Author(s):

Rifat Sabuhi ◽

Quaisar Ali ◽

Mohammad Asghar ◽

Najah Riesh Hadi Al-Zamily ◽

Tahir Hussain

Keyword(s):

Oxidative Stress ◽

Zucker Rats ◽

Kidney Cortex ◽

Sod Activity ◽

Markers Of Inflammation ◽

Tnf Α ◽

Obese Rats ◽

Obese Zucker Rats ◽

And Oxidative Stress

Inflammation and oxidative stress are believed to contribute to hypertension in obesity/diabetes. Recently, we reported a role for the AT2 receptor in blood pressure control in obese Zucker rats. However, the role of AT2 receptors in inflammation and oxidative stress in obesity is not known. Therefore, in the present study, we tested the effects of the AT2 receptor agonist CGP-42112A on inflammation and oxidative stress in obese Zucker rats and compared them in their lean counterparts. Rats were systemically treated with either vehicle (control) or CGP-42112A (1 μg·kg−1·min−1; osmotic pump) for 2 wk. Markers of inflammation (CRP, MCP-1, TNF-α, and IL-6) and oxidative stress (HO-1, gp-91phox) as well as an antioxidant (SOD) were determined. Control obese rats had higher plasma levels of CRP, MCP-1, TNF-α, IL-6, and HO-1 compared with control lean rats. Conversely, plasma SOD activity was lower in control obese than in control lean rats. Furthermore, the protein levels of TNF-α and gp-91phox were higher in the kidney cortex of control obese rats. Interestingly, CGP-42112A treatment in obese rats reduced the plasma and kidney cortex inflammatory (TNF-α, IL-6) and oxidative stress (gp-91phox) markers and increased plasma SOD activity to the levels seen in lean control rats. However, CGP-42112A treatment in lean rats increased inflammatory (TNF-α, IL-6) and oxidative stress (gp-91phox) markers in the plasma and kidney cortex. Our present studies suggest anti-inflammatory and antioxidative functions of AT2 receptor in obese Zucker rats but proinflammatory and prooxidative functions in lean Zucker rats.

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Ox-LDL Aggravates the Oxidative Stress and Inflammatory Responses of THP-1 Macrophages by Reducing the Inhibition Effect of miR-491-5p on MMP-9

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.697236 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yiling Liao ◽

Enzheng Zhu ◽

Wanxing Zhou

Keyword(s):

Oxidative Stress ◽

Gene Silencing ◽

Inflammatory Responses ◽

Mediating Effect ◽

High Expression ◽

Sod Activity ◽

Expression Levels ◽

Inhibition Effect ◽

Protein Levels ◽

Tnf Α

Background: Oxidized low-density lipoprotein (ox-LDL) can induce oxidative stress and inflammatory responses in macrophages to facilitate the genesis and development of atherosclerosis. However, the intermediate links remain unclear. MiR-491-5P can inhibit matrix metalloproteinase 9 (MMP-9); however, it remains unclear whether ox-LDL enhances MMP-9 expression and aggravates the oxidative stress and inflammatory responses under the mediating effect of miR-491-5P.Method: THP-1 macrophages were divided into 10 groups: blank (control), model (ox-LDL), miR-491-5P high-expression (miR-491-5P mimic), miR-491-5P control (mimic-NC), MMP-9 high-expression (MMP-9-plasmid), MMP-9 control (plasmid-NC), miR-491-5P+plasmid-NC, miR-491-5P+ MMP-9-plasmid, MMP-9 gene silencing (MMP-9-siRNA), and gene silencing control (siRNA-NC). The cells were transfected for 48 h and then treated with 50 μg/mL of ox-LDL for 24 h. MMP-9 mRNA and miR-491-5P expression levels in the cells were detected using reverse transcription-quantitative polymerase chain reaction, and the MMP-9 levels were detected with western blotting. The levels of oxidative stress factors (malondialdehyde [MDA]), reactive oxygen species (ROS), and antioxidant factors (superoxide dismutase [SOD]), and the expression levels of inflammatory factors (tumor necrosis factor [TNF-α] and interleukin-1β and−6 [IL-1β and IL-6]) in the supernatant were detected with enzyme-linked immunosorbent assay.Results: MDA, ROS, TNF-α, IL-1β, IL-6, and MMP-9 levels were increased, SOD activity was reduced, and miR-491-5P expression was downregulated in the ox-LDL group compared to the control group. In the miR-491-5P mimic group, the MDA, ROS, TNF-α, IL-1β, IL-6, MMP-9 mRNA and protein levels were downregulated, and SOD activity was enhanced compared to the ox-LDL group. MMP-9-plasmid elevated the MDA, ROS, TNF-α, IL-1β, IL-6, MMP-9 mRNA and protein levels, and downregulated SOD activity and miR-491-5P expression. Following transfection with MMP-9-siRNA, the MMP-9-plasmid outcomes were nullified, and the resulting trends were similar to the miR-491-5p simulation group. Oxidative stress and inflammatory responses were higher in the miR-491-5P mimic+MMP-9-plasmid co-transfection group than in the miR-491-5P mimic group.Conclusion: Ox-LDL aggravates the oxidative stress and inflammatory responses of THP-1 macrophages by reducing the inhibition effect of miR-491-5p on MMP-9.

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Histidine supplementation alleviates inflammation in the adipose tissue of high-fat diet-induced obese rats via the NF-κB- and PPARγ-involved pathways

British Journal Of Nutrition ◽

10.1017/s0007114514001056 ◽

2014 ◽

Vol 112 (4) ◽

pp. 477-485 ◽

Cited By ~ 18

Author(s):

Xiaowei Sun ◽

Rennan Feng ◽

Yanchuan Li ◽

Song Lin ◽

Wei Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

High Fat Diet ◽

Low Grade ◽

Obese Women ◽

Sprague Dawley ◽

High Fat ◽

Tnf Α ◽

Obese Rats ◽

And Oxidative Stress

Obesity is considered to be accompanied by a chronic low-grade inflammatory state that contributes to the occurrence of many chronic diseases. Our previous study has demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women. However, the in vivo potential mechanisms are not known. The present study was conducted to investigate the mechanisms underlying the effects of histidine on inflammation in a high-fat diet (HFD)-induced female obese rat model. An obese model was established in female Sprague–Dawley rats by HFD feeding for 8 weeks and followed by histidine supplementation for another 4 weeks. The results revealed that HFD-increased body weight and HFD-lowered serum histidine concentrations were significantly reversed by histidine supplementation (P< 0·05). In addition, the serum concentrations of TNF-α, IL-6, C-reactive protein (CRP) and malondialdehyde were significantly reduced and those of superoxide dismutase (SOD) were significantly increased by histidine supplementation when compared with those in obese rats (P< 0·05). Correspondingly, the mRNA expressions of TNF-α, IL-6 and CRP in the adipose tissue were significantly down-regulated and that of CuZnSOD was significantly up-regulated by histidine supplementation (P< 0·05). Histidine supplementation significantly reduced the HFD-induced translocation of NF-κB p65 into the nucleus (P= 0·032) by reducing the phosphorylation of the inhibitor of κBα in the adipose tissue. The results also revealed that the expression of adiponectin was markedly increased both in the serum and in the adipose tissue after histidine supplementation, accompanied by the activation of PPARγ (P= 0·021). These findings indicate that histidine is an effective candidate for ameliorating inflammation and oxidative stress in obese individuals via the NF-κB- and PPARγ-involved pathways.

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The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

10.21203/rs.2.16758/v3 ◽

2020 ◽

Author(s):

Jie Guo ◽

Xiaolu Cao ◽

Xianmin Hu ◽

Shulan Li ◽

Jun Wang

Keyword(s):

Oxidative Stress ◽

Terminal Deoxynucleotidyl Transferase ◽

Tunel Staining ◽

Apoptotic Cells ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor

Abstract Background: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats.Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the cerebral homogenates were detected using ELISA assay.Results: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1β and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group.Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

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Protective role of protocatechuic acid in sevoflurane-induced neuron apoptosis, inflammation and oxidative stress in mice

Restorative Neurology and Neuroscience ◽

10.3233/rnn-201022 ◽

2020 ◽

Vol 38 (4) ◽

pp. 323-331

Author(s):

Yuhua Gao ◽

Liping Ma ◽

Tao Han ◽

Meng Wang ◽

Dongmei Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Neuronal Apoptosis ◽

Protocatechuic Acid ◽

Protective Role ◽

Continuous Treatment ◽

Tunel Staining ◽

Neuroprotective Effects ◽

Tnf Α ◽

Pre Treatment ◽

And Oxidative Stress

Background: In neonatal mice, sevoflurane, inspired through the nasal cavity to act as anesthesia, triggers neuronal apoptosis, inflammation and oxidative injury that can hamper cognitive functions in the growth of the central nervous system in the later stages of life. Objective: Our study aimed to explore the potential neuroprotective effects of protocatechuic acid (PCA) to ameliorate neonatal sevoflurane-induced neurotoxicity. Methods: Male mice were pretreated with PCA (10 or 20 mg/kg) for half an hour before continuous treatment for 6 h with 3 % sevoflurane. TUNEL staining was performed to examine the apoptotic cells to record their count. ELISA was performed to evaluate the expressions of the proteins - IL-1β, IL-18 and TNF-α. Analysis of the Western blot and test of the Morris maze was determined and the results analyzed. Results: TUNEL findings assay showed a significant reduction with sevoflurane in neuronal apoptosis treated with PCA at 20 mg/kg. The expression of protein Caspase-3 showed significant changes in the group SEV + PCA (20 mg/kg). ELISA analysis showed that the levels of IL-18 and TNF-α were significantly reduced in the SEV + PCA (20 mg/kg) group as compared to SEV + PCA (10 mg/kg) group. MDA, ROS and SOD levels were noted to decrease significantly only in the SEV + PCA group (20 mg/kg) while IL-1β levels decreased in both SEV + PCA groups (10 or 20 mg/kg) respectively. Conclusions: Our findings imply that apoptosis, inflammation, and oxidative stress in the hippocampal region of neonatal mouse brain were significantly reduced by pre-treatment with PCA before sevoflurane exposure. Therefore, suggesting a role for PCA as a novel therapeutic agent in the treatment of sevoflurane anesthesia-induced neurobehavioral dysfunction.

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Melatonin protects against LPS-induced inflammation and oxidative stress in hepatocytes by enhancing mitophagy and mitochondrial biogenesis

10.21203/rs.3.rs-207360/v1 ◽

2021 ◽

Author(s):

Bin Hu ◽

Zhijiang Chen ◽

Lili Liang ◽

Meiyu Zheng ◽

Yaxin Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Biogenesis ◽

Inflammatory Responses ◽

Experimental Sepsis ◽

Peroxisome Proliferator ◽

Sod Activity ◽

Protein Levels ◽

Atp Levels ◽

Tnf Α

Abstract Background: Melatonin have a protective effect in the liver during sepsis by counteracting oxidative stress and reducing inflammatory responses. Melatonin also regulates mitochondrial biogenesis. This study explored the mechanisms by which melatonin protects against liver injury in experimental sepsis with a focus on mitophagy and mitochondrial biogenesis.Methods and Results: An in vitro model of sepsis-induced hepatocyte injury was established using AML12 cells. Indicators of oxidative stress, inflammation, mitophagy and mitochondrial biogenesis were assessed. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein levels, intracellular reactive oxygen species (ROS) levels, lipid peroxidation (malondialdehyde [MDA] levels), and markers of mitophagy (PTEN-induced putative kinase 1 [PINK1] and Parkin) and mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator 1a [PGC-1α], nuclear respiratory factor 1 [NRF-1], mitochondrial transcription factor A [TFAM]) were significantly increased, while superoxide dismutase (SOD) activity and intracellular adenosine triphosphate (ATP) levels were significantly decreased in LPS-treated AML12 cells compared to controls. TNF-α and IL-6 protein levels and intracellular ROS and MDA levels were significantly decreased, while SOD activity, intracellular ATP levels, and markers of mitophagy and mitochondrial biogenesis were significantly increased by melatonin pre-treatment.Conclusion: This study demonstrated that melatonin was involved in the maintenance of mitochondrial homeostasis in hepatocytes during sepsis. Mechanisms involved selective elimination of dysfunctional mitochondria through mitophagy and induction of mitochondrial biogenesis.

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