Lipid Peroxidation Product Malondialdehyde Research Articles

Sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents ejection fraction reduction, reduces myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity

BackgroundAnthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in patients with cancer. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease, and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i dapagliflozin administered before and during doxorubicin (DOXO) therapy could prevent cardiac dysfunction and reduce pro-inflammatory pathways in preclinical models.MethodsCardiomyocytes were exposed to DOXO alone or combined with dapagliflozin (DAPA) at 10 and 100 nM for 24 h; cell viability, iATP, and Ca++ were quantified; lipid peroxidation products (malondialdehyde and 4-hydroxy 2-hexenal), NLRP3, MyD88, and cytokines were also analyzed through selective colorimetric and enzyme-linked immunosorbent assay (ELISA) methods. Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg), or DOXO combined with DAPA. Systemic levels of ferroptosis-related biomarkers, galectin-3, high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed.ResultsDAPA exerts cytoprotective, antioxidant, and anti-inflammatory properties in human cardiomyocytes exposed to DOXO by reducing iATP and iCa++ levels, lipid peroxidation, NLRP-3, and MyD88 expression. Pro-inflammatory intracellular cytokines were also reduced. In preclinical models, DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in the DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1β, IL-6, TNF-α, G-CSF, and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in the DOXO group; on the other hand, their expression was reduced in the DAPA-DOXO group. Troponin-T, B-type natriuretic peptide (BNP), and N-Terminal Pro-BNP (NT-pro-BNP) were strongly reduced in the DOXO-DAPA group, revealing cardioprotective properties of SGLT2i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression.ConclusionThe overall picture of the study encourages the use of DAPA in the primary prevention of cardiomyopathies induced by anthracyclines in patients with cancer.

Mitochondrial Peroxiredoxin 6 Declines with Aging in Parallel with Increases in Hydrogen Peroxide Generation

Oxidative stress in cells and tissues arise from an imbalance between the generation of free radicals and the ability to detoxify these reactive oxygen species (ROS). Peroxiredoxins (PRDXs) are a family of widely distributed enzymes that act as master antioxidant regulators by scavenging peroxides and peroxynitrites. The accumulation of oxidative damage from chronic exposure to oxidative stress such as on DNA, mitochondrial proteins, and lipid macromolecules, is postulated to result in age-associated pathologies and physiological dysfunctions. Peroxiredoxin-6 (PRDX6) contributes to the maintenance of redox balance in a variety of tissues from lung to skeletal muscle. Here, we hypothesized that PRDX6 localizes to the mitochondria and plays a significant role in maintaining mitochondrial function through targeting mitochondrially generated ROS, and that gradual loss of mitochondrial PRDX6 contributes to increased oxidative stress and accumulation of oxidative damage during aging. In this study, respiratory rates and complex activities in isolated skeletal muscle mitochondria obtained from young (3-6 months) and old (20-24 months) C57/BL6J mice were compared. Amplex UltraRed fluorescence was used to determine production rates of mitochondrial hydrogen peroxide (H2O2). Western blot analysis was used to compare protein abundance and ELISA was used to measure lipid peroxidation in skeletal muscle mitochondrial fractions. Our findings revealed that isolated mitochondria from skeletal muscle in old mice generated higher rates of H2O2 from complex I (CI) during state 3 and state 4 (State 3; State 4) derived respiration (3.93 ± 0.41; 3.56 ± 0.38 pmol H2O2..s−1.mg−1) compared to young mouse mitochondria (1.57 ± 0.48; 1.89 ± 0.59 pmol H2O2.s−1.mg−1, p ≤ 0.05). This was also found when saturating amounts of ADP were used to stimulate maximal rates of oxygen consumption (old: 3.65 ± 0.77; young 1.40 ± 0.21 pmol H2O2−1.mg−1, p ≤ 0.05). Furthermore, CI activity was found to be lower in isolated mitochondria from old mice (0.65 ± 0.006 U.ug−1) compared to young mice (2.11 ± 0.64 U.ug−1, p ≤ 0.05). Similarly, mitochondrial PRDX6 abundance was lower while levels of lipid peroxidation product malondialdehyde were higher in skeletal muscle from old animals (old: 2712 ± 1320 pg.mL−1; young: 489 ± 225 pg.mL−1). These results show higher mitochondrial ROS generation rates and oxidative damage in old animals. These data also suggest that loss of PRDX6 in aging leads to mitochondrial dysfunction mediated by diminished CI activity and loss of membrane integrity. We are currently conducting mechanistic studies in cellular models with disrupted PRDX6 expression to confirm the effect of this protein in maintaining mitochondrial function. This study offers novel observations on the significance of mitochondrially localized PRDX6 in antioxidant defense as well as the sources and roles of ROS generation in contributing to an aging phenotype. National Institute of General Medical Sciences (NIGMS, Award Number R35GM146951). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of two typical quinolone antibiotics in the marine environment on Skeletonema costatum

This study investigated the effects of levofloxacin (LEV) and norfloxacin (NOR) on Skeletonema costatum, focusing on cell growth, chlorophyll a (Chla) content, maximal quantum yield of PSII (Fv/Fm), protein content, enzyme activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GSH-PX), and the membrane lipid peroxidation product malondialdehyde (MDA) content were conducted to analyze the responses of S. costatum under LEV and NOR exposure. Cell growth, Chla content, Fv/Fm, protein content, enzyme activities, and MDA content were assessed to elucidate physiological changes. Both LEV and NOR inhibited S. costatum growth, except for 10 mg/L NOR, which promoted growth. Algal cells exhibited higher sensitivity to LEV, with 96h-IC50 values of 14.770 mg/L for LEV and 44.250 mg/L for NOR. Low NOR concentration (10 mg/L) increased Chla content, while high antibiotic concentrations (>20 mg/L for LEV, >100 mg/L for NOR) decreased Chla content and Fv/Fm, indicating an impact on photosynthesis. Elevated LEV and NOR levels reduced protein and MDA content but increased GR, SOD, and GSH activities, indicating induced oxidative stress. The study provides a comprehensive analysis of LEV and NOR effects on marine microalgae growth and underlying physiological mechanisms, shedding light on potential ecological risks posed by antibiotics in marine ecosystems.

Ameliorative Effect of Cinnamon and Rosemary Oils in Acrylamide–Induced Hepatic Injury in Rats

Liver diseases can result from various causes, such as viruses, bacteria, autoimmune disorders, or certain medications and toxic substances. While modern medicine offers treatments for these conditions, there needs to be more effective drugs that can protect and regenerate liver cells. Therefore, it is crucial to identify new treatment options and liver-protective agents that are both highly efficient and safe. This study is assigned to investigate the adverse effects of acrylamide on the liver in rats and explore whether these effects can be mitigated by co-administration of cinnamon oil (C.O.), rosemary oil (R.O.), or a combination of both oils during acrylamide exposure. A total of 70 male albino rats were divided randomly into 7 groups, each group of 10 rats, that received different treatments: control group, acrylamide-treated group (20 mg/kg b.wt), cinnamon oil-treated group (200 mg/kg b.wt), rosemary oil-treated group (250 mg/kg b.wt), acrylamide and cinnamon oil-treated group, acrylamide and rosemary oil-treated group, and acrylamide, cinnamon oil, and rosemary oil-treated group. These treatments were administered orally for 28 consecutive days. Blood and liver tissue samples were gathered at the end of the study to assess the outcomes. The results revealed that cinnamon oil and rosemary oils exhibited hepatoprotective effects, as evidenced by normalized liver function parameters (alanine transaminase, Aspartate transaminase, and Alkaline phosphatase), as well as improvements in nonenzymatic parameters (total protein, albumin, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein). The observed hepatoprotection of cinnamon oil and rosemary oils was attributed to their ability to reduce oxidative stress caused by acrylamide, as demonstrated by lower levels of liver cell lipid peroxidation product (malondialdehyde) and enhanced activity of antioxidative enzymes (glutathione and catalase) in liver tissue. Keywords: Cinnamon, Rosemary, Acrylamide, Liver, Rats, Antioxidants.

Ameliorative Effect of Cinnamon and Rosemary Oils in Acrylamide–Induced Hepatic Injury in Rats

Liver diseases can result from various causes, such as viruses, bacteria, autoimmune disorders, or certain medications and toxic substances. While modern medicine offers treatments for these conditions, there needs to be more effective drugs that can protect and regenerate liver cells. Therefore, it is crucial to identify new treatment options and liver-protective agents that are both highly efficient and safe. This study is assigned to investigate the adverse effects of acrylamide on the liver in rats and explore whether these effects can be mitigated by co-administration of cinnamon oil (C.O.), rosemary oil (R.O.), or a combination of both oils during acrylamide exposure. A total of 70 male albino rats were divided randomly into 7 groups, each group of 10 rats, that received different treatments: control group, acrylamide-treated group (20 mg/kg b.wt), cinnamon oil-treated group (200 mg/kg b.wt), rosemary oil-treated group (250 mg/kg b.wt), acrylamide and cinnamon oil-treated group, acrylamide and rosemary oil-treated group, and acrylamide, cinnamon oil, and Rosemary oil-treated group. These treatments were administered orally for 28 consecutive days. Blood and liver tissue samples were gathered at the end of the study to assess the outcomes. The results revealed that cinnamon oil and rosemary oils exhibited hepatoprotective effects, as evidenced by normalized liver function parameters (alanine transaminase, Aspartate transaminase, and Alkaline phosphatase), as well as improvements in nonenzymatic parameters (total protein, albumin, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein). The observed hepatoprotection of cinnamon oil and rosemary oils was attributed to their ability to reduce oxidative stress caused by acrylamide, as demonstrated by lower levels of liver cell lipid peroxidation product (malondialdehyde) and enhanced activity of antioxidative enzymes (glutathione and catalase) in liver tissue. Keywords: Cinnamon, Rosemary, Acrylamide, Liver, Rats, Antioxidants

GOLPH3 promotes tumor malignancy via inhibition of ferroptosis by upregulating SLC7A11 in cholangiocarcinoma.

Golgi phosphoprotein 3 (GOLPH3) has been reported as an oncogene in various tumors; however, the role and function of GOLPH3 and its relevant molecular mechanism in cholangiocarcinoma (CCA) are unclear. Herein, GOLPH3 expression in CCA tissues was observed to be significantly higher than that in paired adjacent noncancerous tissues. Clinicopathological analysis showed that GOLPH3 expression correlated positively with the tumor-node-metastasis stage. In addition, GOLPH3 expression correlated inversely with the overall survival of patients with CCA. Multivariate analysis showed that GOLPH3 was an independent prognostic factor for patients with CCA. Transcriptome analysis (RNA sequencing) of GOLPH3 knockdown cells showed that the expression levels of nine ferroptosis-related genes were significantly changed, indicating the important biological function of GOLPH3 in ferroptosis in CCA cells. Furthermore, GOLPH3 knockdown could significantly promote Erastin-induced ferroptosis in vitro and suppress tumor growth in vivo. Overexpression of GOLPH3 had the opposite effect on this phenotype. Further studies revealed that GOLPH3 knockdown was significantly associated with a decrease in cysteine content, an accumulation of the lipid peroxidation product malondialdehyde, an increase in reactive oxygen species, and sensitized CCA cells to Erastin-induced ferroptosis. Moreover, changes in GOLPH3 expression were found to be consistent with the expression of light chain subunit solute carrier family 7 member 11 (SLC7A11). Thus, our study suggested that GOLPH3 functions as an oncoprotein in CCA and may suppress ferroptosis by facilitating SLC7A11 expression, suggesting that GOLPH3 could serve as a therapeutic target for CCA treatment.

Excessive dietary iron exposure increases the susceptibility of largemouth bass (Micropterus salmoides) to Aeromonas hydrophila by interfering with immune response, oxidative stress, and intestinal homeostasis

Iron is an essential cofactor in the fundamental metabolic pathways of organisms. Moderate iron intake can enhance animal growth performance, while iron overload increases the risk of pathogen infection. Although the impact of iron on the pathogen-host relationship has been confirmed in higher vertebrates, research in fish is extremely limited. The effects and mechanisms of different levels of iron exposure on the infection of Aeromonas hydrophila in largemouth bass (Micropterus salmoides) remain unclear. In this study, experimental diets were prepared by adding 0, 800, 1600, and 3200 mg/kg of FeSO4∙7H2O to the basal feed, and the impact of a 56-day feeding period on the mortality rate of largemouth bass infected with A. hydrophila was analyzed. Additionally, the relationships between mortality rate and tissue iron content, immune regulation, oxidative stress, iron homeostasis, gut microbiota, and tissue morphology were investigated. The results showed that the survival rate of largemouth bass infected with A. hydrophila decreased with increasing iron exposure levels. Excessive dietary iron intake significantly increased iron deposition in the tissues of largemouth bass, reduced the expression and activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, increased the content of lipid peroxidation product malondialdehyde, and thereby induced oxidative stress. Excessive iron supplementation could influence the immune response of largemouth bass by upregulating the expression of pro-inflammatory cytokines in the intestine and liver, while downregulating the expression of anti-inflammatory cytokines. Additionally, excessive iron intake could also affect iron metabolism by inducing the expression of hepcidin, disrupt intestinal homeostasis by interfering with the composition and function of the gut microbiota, and induce damage in the intestinal and hepatic tissues. These research findings provide a partial theoretical basis for deciphering the molecular mechanisms underlying the influence of excessive iron exposure on the susceptibility of largemouth bass to pathogenic bacteria.

Arsenic trioxide induces ferroptosis in neuroblastoma by mediating GPX4 transcriptional inhibition.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood, significantly contributes to cancer-related mortality, presenting a dearth of efficacious treatment strategies. Previously, our studies have substantiated the potent cytotoxicity of arsenic trioxide (ATO) against NB cells, however, the specific underlying mechanism remains elusive. Here, we first identified ATO as a novel GPX4 inhibitor, which could trigger the ferroptosis in NB cells. Invitro, ATO significantly inhibited the proliferation and migration ability of NB cells SK-N-AS and SH-SY5Y, and induced ferroptosis. Furthermore, the iron chelator deferoxamine reversed ATO-mediated intracellular reactive oxygen species accumulation and hindered the generation of the lipid peroxidation product malondialdehyde. Conversely, ferric ammonium citrate notably intensified its cytotoxic effects, especially on retinoic acid (RA)-resistant SK-N-AS cells. Subsequently, the quantitative real-time polymerase chain reaction results showed ATO significantly inhibited the transcription of GPX4 in NB cells. Remarkably, immunoblotting analysis revealed that MG132 exhibited a notable effect on elevating GPX4 levels in NB cells. Nevertheless, pretreatment with MG132 failed to reverse the ATO-mediated decrease in GPX4 levels. These findings suggested that ATO reduced the GPX4 expression level in NB cells by mediating GPX4 transcriptional repression rather than facilitating ubiquitinated degradation. In conclusion, our research has successfully indicated that ATO could induce ferroptosis and initiate lipid peroxidation by regulating the transcriptional repression of GPX4, and ATO holds promise as a potential anti-tumor agent in NB, specifically for patients with RA-resistant HR-NB.

Effects of Duloxetine on Oxidant-Antioxidant System in Rat Brain Tissues

Objective: After the relationship between depression and oxidative stress (OS) was demonstrated, the effect of antidepressant drugs on OS has become important. In this study, we aimed to determine the effects of the antidepressant duloxetine on the activities of the superoxide dismutase (SOD), catalase (CAT), adenosine deaminase (ADA), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) enzymes as well as the lipid peroxidation (LP) product malondialdehyde (MDA) and nitric oxide (NO) levels in rat brains. 
 Material and Method: Twenty male Sprague-Dawley rats were used for the study. The first group was the control group (n=10) and the second group was the duloxetine group (n=10). Duloxetine was administered intragastrically once a day at a dose of 10 mg/kg for two weeks in the second group. Water was administered intragastrically once a day for two weeks in the first group. Rats were sacrificed at the end of the fourteenth day. The brain tissues were collected and then analyzes were performed.
 Results: As a result of this study, we found that duloxetine increased the SOD (P=0.026) activity and decreased the ADA (P=0.041), XO (P=0.034) and CAT (P=0.006) activities significantly compared to the control group. We also found an increase in the GSH-Px enzyme activity and decrease in the NO and MDA levels at non-significant rates in the duloxetine group brain tissues.
 Conclusion: The significant increase in the activity of the antioxidant enzyme SOD, the significant decrease in the activities of the XO and ADA enzymes, which can cause the formation of reactive oxygen products in the organism, and the insignificant decrease in the LP indicator MDA suggest that duloxetine can positively change the antioxidant status in rat brain tissues.

Effect of niclosamide on colorectal cancer induced by dimethylhydrazine in albino mice

ABSTRACTColorectal cancer (CRC) is a prevalent cancer worldwide, and its incidence has increased in recent years. 1,2-Dimethylhydrazine (DMH) is a carcinogenic alkylating agent that causes tumors in various organs, particularly the distal colon. Niclosamide (Nic) disrupts oxidative phosphorylation and lowers ATP levels in tumor cells. This study aimed to investigate the potential protective effects of Nic against DMH-induced CRC in male albino mice through histopathological, immunohistochemical, and biochemical analyses. The study involved subcutaneous injections of DMH at a dose of 15 μg/g administered twice weekly for six weeks, alone or in combination with Nic injections of 20 mg/kg twice weekly for six weeks. The colorectal paraffin slides were subjected to histopathology and apoptosis-inducing factor (AIF) immunostaining, and colorectal homogenate samples were used to measure the lipid peroxidation products malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG).The results indicated that Nic injections reduced collagen deposition and AIF staining intensity in paraffin slides and decreased MDA content and 8-OHdG levels in tissue homogenates.These findings suggest that Nic injections may have an anti-CRC effect.

Selenomethionine protects the liver from dietary deoxynivalenol exposure via Nrf2/PPARγ-GPX4-ferroptosis pathway in mice

Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dismutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accumulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor γ (PPARγ), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPARγ-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution.

Lipid from electronic cigarette-aerosol both with and without nicotine induced pro-inflammatory macrophage polarization and disrupted phagocytosis

Clinical cases and experimental evidence revealed that electronic cigarettes (ECIG) induce serious adverse health effects, but underlying mechanisms remain to be fully uncovered. Based on recent exploratory evidence, investigating the effects of ECIG on macrophages can broadly define potential mechanisms by focusing on the effect of ECIG exposure with or without nicotine. Here we investigated the effect of ECIG-aerosol exposure on macrophages (MQ) phenotype, inflammatory response, and function of macrophages.MQ were cultured at air liquid interface and exposed to ECIG-aerosol. Oxidative stress was determined by reactive oxygen species (ROS), heat shock protein 60 (HSP60), glutathione peroxidase (GPx) and heme oxygenase1 (HMOX1). Lipid accumulation and lipid peroxidation were defined by lipid staining and level of malondialdehyde (MDA) respectively. MQ polarization was identified by surface expression markers CD86, CD11C and CD206 as well as pro-inflammatory and anti-inflammatory cytokines in gene and protein level. Phagocytosis of E. coli by MQ was investigated by fluorescence-based phagocytosis assay.ECIG-aerosol exposure in presence or absence of nicotine induced oxidative stress evidenced by ROS, HSP60, GPx, GPx4 and HMOX1 upregulation in MQ. ECIG-aerosol exposure induced accumulation of lipids and the lipid peroxidation product MDA in MQ. Pro-inflammatory MQ (M1) markers CD86 and CD11C but not anti-inflammatory MQ (M2) marker CD206 were upregulated in response to ECIG-aerosol exposure. In addition, ECIG induced pro-inflammatory cytokines IL-1beta and IL-8 in gene level and IL-6, IL-8, and IL-1beta in protein level whereas ECIG exposure downregulated anti-inflammatory cytokine IL-10 in protein level. Phagocytosis activity of MQ was downregulated by ECIG exposure. shRNA mediated lipid scavenger receptor ‘CD36’ silencing inhibited ECIG-aerosol-induced pro-inflammatory MQ polarization and recovered phagocytic activity of MQ.ECIG exposure alters lung lipid homeostasis and thus induced inflammation by inducing M1 type MQ and impair phagocytic function, which could be a potential cause of ECIG-induced lung inflammation in healthy and inflammatory exacerbation in disease condition.

Lipid Peroxidation via Regulating the Metabolism of Docosahexaenoic Acid and Arachidonic Acid in Autistic Behavioral Symptoms.

The association between the lipid peroxidation product malondialdehyde (MDA)-modified low-density lipoprotein (MDA-LDL) and the pathophysiology of autism spectrum disorder (ASD) is unclear. This association was studied in 17 children with ASD and seven age-matched controls regarding autistic behaviors. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC). To compensate for the small sample size, adaptive Lasso was used to increase the likelihood of accurate prediction, and a coefficient of variation was calculated for suitable variable selection. Plasma MDA-LDL levels were significantly increased, and plasma SOD levels were significantly decreased in addition to significantly increased plasma docosahexaenoic acid (DHA) levels and significantly decreased plasma arachidonic acid (ARA) levels in the 17 subjects with ASD as compared with those of the seven healthy controls. The total ABC scores were significantly higher in the ASD group than in the control group. The results of multiple linear regression and adaptive Lasso analyses revealed an association between increased plasma DHA levels and decreased plasma ARA levels, which were significantly associated with total ABC score and increased plasma MDA-LDL levels. Therefore, an imbalance between plasma DHA and ARA levels induces ferroptosis via lipid peroxidation. Decreased levels of α-linolenic acid and γ-linolenic acid may be connected to the total ABC scores with regard to lipid peroxidation.

β-lapachone protects against doxorubicin-induced hepatotoxicity through modulation of NAD+ /SIRT-1/FXR/p-AMPK/NF-kB and Nrf2 signaling axis.

Doxorubicin (DOX)is a widely used antineoplastic drug, but its clinical use is limited by significant toxicities, such as hepatotoxicity. In this study, we evaluated the effects of β-lapachone (β-LAP),a natural quinone-containing compound, in a mouse model of DOX-induced hepatotoxicity. β-LAPwas orally administered at 1.25, 2.5, and 5 mg/kg for 4 days, and a single dose of DOX (20 mg/kg) was injected intraperitoneally on the second day. Histopathological changes, liver function markers, antioxidant and inflammatory markers were assessed. β-LAPameliorated liver injury and liver function markers evoked by DOX. β-LAP also downregulated the mRNA expression of nuclear factor-kB-corresponding genes including interleukin-6, interleukin-1β, and tumor necrosis factor-α. Moreover, β-LAPincreased the nuclear factor erythroid 2-related factor 2 target genes heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1, along with antioxidant enzymes including reduced glutathione, catalase, and superoxide dismutase with simultaneous reduction in the lipid peroxidation product malondialdehyde. Meanwhile, it recovered NAD+ /NADH ratios and subsequently elevated the protein levels of sirtuin-1 (SIRT-1),farnesoid X receptor (FXR),and phosphorylated AMP-activated protein kinase (p-AMPK).Collectively, these findings suggest a protective role of β-LAPagainst DOX-induced hepatotoxicity by partly regulating the NAD+ /SIRT-1/FXR/p-AMPKaxis.

Effect of L-proline on sperm quality during cryopreservation of boar semen

L-proline has been reported to be useful in semen cryopreservation. However, its use has rarely been reported in the freezing of boar semen. The objective of this study was to evaluate the effects of different concentrations of L-proline (0, 10, 30, 50, and 90 mM) on the quality of boar semen after freezing and thawing. Semen samples from boars (n = 6) were frozen using freezing extenders with added concentrations of L-proline. Total sperm motility, progressive motility, survival time at 37 °C, acrosome integrity, mitochondrial activity, DNA integrity, the content of the lipid peroxidation product malondialdehyde (MDA), total antioxidant capacity (T-AOC) and, expression levels of apoptosis protein (cleaved caspase 3 and Bax) were evaluated after thawing. The results showed that total sperm viability (73.96% vs. 63.58%) and progressive motility (56.88% vs. 47.26%) after thawing were significantly higher in the 10 mM L-proline treatment group than in the control group. The survival time at 37 °C and the total motility of sperm in the 10 mM group within one hour after thawing were significantly higher than in the control group. Acrosome integrity and mitochondrial activity of sperm in the 10 mM group were significantly higher than those in the control, 50 mM, and 90 mM groups. The DNA integrity rate in the 10 mM group was significantly higher than in the control group. The L-proline treatment did not affect sperm MDA content or T-AOC. The expression levels of apoptosis protein (cleaved caspase 3 and Bax) in the 10 mM L-proline supplemented group were lower than those in the control group. In conclusion, the freezing extender containing 10 mM L-proline improved semen quality after freezing and thawing and thus would be a useful reagent for boar semen cryopreservation.

Long-Chain Alkylphenol Biodegradation Potential of Soil Ascomycota

A total of 11 ascomycete strains destructing technical nonylphenol (NP) and 4-tert-octylphenol (4-t-OP) were isolated from NP-contaminated soddy-podzolic loamy soil (Leningrad Region, Russia). The isolates proved capable of degrading NP and 4-t-OP at a high load (300 mg/L). The most efficient Fusarium solani strain 8F degraded alkylphenols (APs) both in cometabolic conditions and in the absence of additional carbon and energy sources. A decrease in APs was due to biodegradation or biotransformation by the strain and, to a minor extent, absorption by fungal cells. NP and 4-t-OP half-lives were, respectively, 3.5 and 6.4 h in cometabolic conditions and 9 and 19.7 h in the absence of additional carbon and energy sources. Amounts of the lipid peroxidation product malondialdehyde (MDA) and reduced glutathione (GSH) increased during NP and 4-t-OP biodegradation in cometabolic conditions by 1.7 and 2 times, respectively, as compared with a control. A high GSH level in F. solani 8F cells potentially implicated the metabolite in both AP biodegradation and strain resistance to oxidative stress. The study is the first to report on the NP and 4-t-OP degradation by the ascomycete F. solani in cometabolic conditions and in the absence of additional carbon and energy sources. The high AP degradation potential of soil ascomycetes was assumed to provide a basis for new environmentally safe bioremediation technologies for purification of soils and natural and waste waters contaminated with endocrine disruptors.

Corn Silk Polysaccharides with Different Carboxyl Contents Reduce the Oxidative Damage of Renal Epithelial Cells by Inhibiting Endocytosis of Nano-calcium Oxalate Crystals.

Renal epithelial cell injury and cell-crystal interaction are closely related to kidney stone formation. This study aims to explore the inhibition of endocytosis of nano-sized calcium oxalate monohydrate (nano-COM) crystals and the cell protection of corn silk polysaccharides (CCSPs) with different carboxyl contents (3.92, 7.75, 12.90, and 16.38%). The nano-COM crystals protected or unprotected by CCSPs were co-cultured with human renal proximal tubular epithelial cells (HK-2), and then the changes in the endocytosis of nano-COM and cell biochemical indicators were detected. CCSPs could inhibit the endocytosis of nano-COM by HK-2 cells and reduce the accumulation of nano-COM in the cells. Under the protection of CCSPs, cell morphology is restored, intracellular superoxide dismutase levels are increased, lipid peroxidation product malondialdehyde release is decreased, and mitochondrial membrane potential and lysosomal integrity are increased. The release of Ca2+ ions in the cell, the level of cell autophagy, and the rate of cell apoptosis and necrosis are also reduced. CCSPs with higher carboxyl content have better cell protection abilities. CCSPs could inhibit the endocytosis of nano-COM crystals and reduce cell oxidative damage. CCSP3, with the highest carboxyl content, shows the best biological activity.

Establishment of insomnia model of chronic unpredictable stress in rats

It is well known that stressful situation is one of the important factors causing insomnia, however, the underlying mechanism is still elusive. Therefore, the establishment of a suitable animal model of stress insomnia will be of great help to solve this problem. In this study, by combining with chronic unpredictable stress (multitude of stressors) and sleep deprivation, we attempted to establish a rat model of stress insomnia. It was observed that rats with stress insomnia showed significant weight loss, and less sleep quality in pentobarbital sodium induced sleep test and electroencephalogram detection. Moreover, rats with stress insomnia showed greater depression and anxiety detected by forced swimming, sucrose preference test and open field. Since oxidative stress has been reported to be involved in insomnia, we further evaluated the production of oxidative stress and found that the levels of lipid peroxidation product malondialdehyde (MDA) in liver, serum total bilirubin and urine biopyrrin were all significantly increased in rats with stress insomnia. In addition, we also found that the memory of these rats with stress insomnia was also obviously reduced in water maze. Taken together, these results demonstrate that the emotional behaviors, memory, oxidative and metabolism of the rats were all significantly changed after modeling, indicating a rat model of stress insomnia was successful establishment, and this animal model will provide basis to further explore the underlying mechanism of chronic stress in insomnia.

Seed priming with Beauveria bassiana improves growth and salt stress response in rice

One of the most important abiotic factors that hinder plant development, growth, and production is salt stress. In recent years, there has been a lot of interest in the biological treatment of salt stress in plants using beneficial microbes. The fungal endophyte Beauveria bassiana provides a wide variety of ecosystem services, like suppressing insect pests and pathogens and enhancing plant growth. However, the role of B. bassiana in reducing salt stress in plants has not yet been clarified. This study was undertaken to evaluate the performance of B. bassiana isolate BeauA1 primed rice under salt stress by estimating rice growth, stress parameters, and mitigator characteristics. Primarily, rice seeds were primed with BeauA1 and placed in an agar medium with 120 mM NaCl (≈12 dS m−1 salt solution) to observe the role of BeauA1 in the early establishment of rice seedlings in salt conditions. Seed priming with BeauA1 resulted in an enhancement of rice growth attributes under both control and NaCl stress conditions. In the pot experiment, the BeauA1 primed rice seedlings were planted in soil with different concentrations of salt, viz. 8, 10, and 12 dS m−1. The BeauA1 primed rice plants showed improvement in leaf succulence, leaf area, photosynthetic pigments, and shoot relative water content (RWC), leading to enhanced growth under both salt stress and control conditions. The biochemical study found that BeauA1 considerably increased proline content, total soluble sugars, total carbohydrates, and K+/Na+ in leaves. The antioxidant enzymes catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), glutathione S-transferase (GST), and nonenzymatic antioxidants phenol and flavonoid were upregulated in BeauA1-primed plants under both control and stressed conditions. Further significant reductions of the lipid peroxidation products malondialdehyde (MDA) and hydrogen peroxide (H2O2) by BeauA1 under salt stress were consistent with higher antioxidant activities in salt stress conditions. Principal component analysis (PCA) further validated BeauA1-primed plants' modulation of growth, antioxidant defense, and reduction of MDA and H2O2 in rice under salt-stress conditions. Our findings indicated that utilizing BeauA1 to reduce salt stress would be a useful strategy to increase rice yield in salt-affected regions.

Inhibition of Connexin43 Improves the Recovery of Spinal Cord Injury Against Ferroptosis via the SLC7A11/GPX4 Pathway

Ferroptosis plays a key role in the process of spinal cord injury (SCI). As a signal amplifier, connexin 43 (CX43) participates in cell death signal transduction and aggravates the propagation of injury. However, it remains unclear whether CX43 plays a regulatory role in ferroptosis after SCI. The SCI rat model was established by an Infinite Vertical Impactor to investigate the role of CX43 in SCI-induced ferroptosis. Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, and a CX43-specific inhibitor (Gap27) were administered by intraperitoneal injection. Behavioral analysis was assessed according to the Basso-Beattie-Bresnahan (BBB) Motor Rating Scale and the inclined plate test. The levels of ferroptosis-related proteins were estimated by qRT-PCR and western blotting, while the histopathology of neuronal injury induced by SCI was evaluated by immunofluorescence, Nissl, FJB and Perl’s Blue staining. Meanwhile, transmission electron microscopy was used to observe the ultrastructural changes characteristic of ferroptosis. Gap27 strongly inhibited ferroptosis and therefore improved the functional recovery of SCI, which was similar to the treatment of Fer-1. Notably, the inhibition of CX43 decreased P-mTOR/mTOR expression and reversed the decrease in SLC7A11 induced by SCI. As a result, the levels of GPX4 and glutathione (GSH) increased, while the levels of the lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) decreased. Together, inhibition of CX43 could alleviate ferroptosis after SCI. These findings reveal a potential mechanism of the neuroprotective role of CX43 after SCI and provide a new theoretical basis for clinical transformation and application.