Levels Of Antioxidant Enzymes Research Articles

Tibetan-Origin Edible Chinese Herbal Prescription C18 Protects H9C2 Cardiomyocytes from Cobalt Chloride-induced Hypoxia Injury Through the PI3K/AKT Signaling Pathway

Background Altitude sickness is often prone to occur during tourism or work in high-altitude areas. In China, traditional Tibetan medicines have a long history of preventing or treating altitude sickness, especially altitude hypoxia, which may lead to myocardial cell apoptosis and myocardial hypoxia-reoxygenation injury. Purpose This study investigated the effect of a Tibetan-origin edible Chinese herbal prescription (named C18) on protecting H9C2 cardiomyocytes from cobalt chloride-induced hypoxia injury and its potential mechanism. Methods In this study, a hypoxic injury model of H9C2 cardiomyocytes induced by cobalt chloride was established first. Then the cell viability, relevant antioxidant indicators malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and protein expression (hypoxia-inducible factor 1 alpha (HIF-1α), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-AKT)) were measured after pretreatment with or without C18. At last, the specific PI3K/AKT inhibitor LY294002 was applied to verify the antihypoxia signaling pathway. Results C18 could significantly promote normal H9C2 cardiomyocyte proliferation and inhibit apoptosis of hypoxic H9C2 cardiomyocytes, reduce the release of lactate dehydrogenase and MDA, and increase the levels of SOD and GSH-Px antioxidant enzymes. In addition, C18 could significantly downregulate the expression of HIF-1α protein and upregulate the expression of intracellular p-AKT. Moreover, these effects of C18 can be blocked by the specific PI3K/AKT inhibitor LY294002. Conclusion C18 protects H9C2 cardiomyocytes from cobalt chloride-induced hypoxia injury through the PI3K/AKT signaling pathway.

SIRT1/AMPK-mediated pathway: Ferulic acid from sugar beet pulp mitigating obesity-induced diabetes-linked complications and improving metabolic health

Obesity-induced type 2 diabetes (T2D) increases the risk of metabolic syndrome due to the high calorie intake. The role of sugar beet pulp (SBP) in T2D and the mechanism of its action remain unclear, though it is abundant in phenolics and has antioxidant activity. In this study, we isolated and purified ferulic acid from SBP, referred to as SBP-E, and studied the underlying molecular mechanisms in the regulation of glucose and lipid metabolism developing high glucose/high fat diet-induced diabetic models in vitro and in vivo. SBP-E showed no cytotoxicity and reduced the oxidative stress by increasing glutathione (GSH) in human liver (HepG2) and rat skeletal muscle (L6) cells. It also decreased body weight gain, food intake, fasting blood glucose levels (FBGL), glucose intolerance, hepatic steatosis, and lipid accumulation. Additionally, SBP-E decreased the oxidative stress and improved the antioxidant enzyme levels in high-fat diet (HFD)-induced T2D mice. Further, SBP-E reduced plasma and liver advanced glycation end products (AGEs), malondialdehyde (MDA), and pro-inflammatory cytokines, and increased anti-inflammatory cytokines in HFD-fed mice. Importantly, SBP-E significantly elevated AMPK, glucose transporter, SIRT1 activity, and Nrf2 expression and decreased ACC activity and SREBP1 levels in diabetic models. Collectively, our study results suggest that SBP-E treatment can improve obesity-induced T2D by regulating glucose and lipid metabolism via SIRT1/AMPK signalling and the AMPK/SREBP1/ACC1 pathway.

Diclofenac Induced Hepatorenal Toxicity on Albino Rats: The Assessment of Mitigative Potential of Fermented Carica Papaya Juice

In a study investigating the protective effects of an extract on diclofenac-induced liver and kidney injuries in Wistar rats, twenty healthy adult Wistar rats weighing between 110g to 200g were randomly divided into four groups of five rats each. Group 1 Control group: received distilled water and standard feed, Group 2 Diclofenac group: administered 10mg/kg body weight of diclofenac., Group 3 Diclofenac + Pawpaw extract group: received diclofenac and post-treated with 200mg/kg body weight of fermented unripe Carica papaya juice, and Group 4 Pawpaw extract group: administered 200mg/kg body weight of fermented unripe Carica papaya juice. The plant extract and diclofenac were orally given over a duration of fourteen (14) days. After the treatment was finished, samples of blood and tissue were collected to analyze the liver function parameters (superoxide dismutase, catalase, and glutathione reductase) (Alanine aminotransferase - ALT, and alkaline phosphatase - ALP), renal function parameters (creatinine), oxidative stress markers, and for histological evaluation. The results showed that diclofenac administration caused a significant increase (p<0.05) in serum levels of ALT and ALP, creatinine and a significant decrease (p<0.05) in antioxidant enzymes (superoxide dismutase, catalase, and glutathione reductase) compared to the control group. However, treatment with FUPJ significantly reduced (p<0.05) the levels of ALT and ALP, creatinine, and MDA and increased (p<0.05) the levels of antioxidant enzymes. In conclusion, FUPJ has the potential to ameliorate diclofenac-induced hepatic and renal dysfunction through its antioxidant and anti-inflammatory properties.

Alleviating Ulcer Burdens Examining the Potential of Albizia Odoratissima Bark Extract as a Therapeutic Agent in Mice

Ulcerative stomach disease continues to be a prevalent gastrointestinal illness associated with high worldwide morbidity and medical costs. While nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are well-known risk factors for the development of peptic ulcers, recent evidence suggests a complex interaction between host factors and the gut microbiota in ulcer etiology. This study provides a comprehensive review of recent research investigating the relationship between the genesis and progression of peptic ulcers and dysbiosis of the gut microbiota. The study highlights several natural compounds, such as flavonoids, polyphenols, alkaloids, and polysaccharides, that have demonstrated anti-ulcer activity in experimental models and clinical trials. Mechanistic understanding clarifies the many pathways, including antibacterial, anti-inflammatory, and antioxidant ones, through which these drugs perform their medicinal effects. It is interesting to note that many natural compounds focus on many pathogenic procedures that aid in the development and spread of ulcers, resulting in multifactorial effects. Albizia odoratissima is a member of the Fabaceae family and has been used traditionally in many folk medicines due to its medicinal characteristics. This study used experimental models of stomach ulceration to investigate potential anti-ulcer properties of methanolic bark extract from Albizia odoratissima (MAO). The anti-ulcer qualities of MAO were evaluated in rats using models of stomach ulceration brought on by HCL. Many parameters were assessed when different doses of MAO were administered orally, including the ulcer index, mucosal injury to the stomach, mucin content, and antioxidant enzyme levels. Additionally, a histological analysis was carried out to evaluate the possible protective qualities of MAO against harm to the stomach mucosa.

Evaluation of antioxidant enzyme levels, oxidative stress markers and serum prolidase activity in testicular cancer.

Testicular cancer is a significant malignancy affecting males, and understanding the underlying biochemical changes associated with the disease is essential for improved management and treatment strategies. Prolidase enzyme, has been implicated in various disease processes. The assessment of serum prolidase activity and its relationship with testicular cancer can provide valuable insights into the pathophysiology of the disease. The objective of this study was to investigate serum prolidase activity, oxidative stress markers, and antioxidant enzyme levels in patients with testicular cancer and evaluate their potential associations, aiming to enhance our understanding of the biochemical alterations and potential implications for testicular cancer management. A total of 33 male patients diagnosed with testicular cancer were included, along with 35 age-matched male volunteers as the control group. Serum samples were collected and stored at -20°C until analysis. The measurement of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), malondialdehyde (MDA), glutathione (GSH), and prolidase levels was performed. The findings demonstrated significantly elevated serum prolidase activity and malondialdehyde (MDA) levels in testicular cancer patients compared to the control group (all, p < 0.05). Conversely, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and glutathione-S-transferase (GST) levels were significantly lower in testicular cancer patients (p < 0.05). In this study, serum prolidase activity and biochemical markers associated with oxidative stress were investigated in testicular cancer patients. Oxidative stress markers and serum prolidase activity were found to be elevated in testicular cancer. Long-term prospective studies are needed to determine the effectiveness of antioxidant use in cancer treatment.

Chamuangone-enriched rice bran oil ameliorates neurodegeneration in haloperidol-induced Parkinsonian rat model via modulation of neuro-inflammatory mediators and suppression of oxidative stress markers

A natural bioactive compound chamuangone extracted from Thai salad Garcinia cowa leaves exhibited robust medicinal properties, targeting central oxidative stress pathways, and having neuroprotective potential. Chamuangone-enriched rice bran oil (CERBO), with 1.97 mg/mL chamuangone, was obtained through green extraction. The study was designed to evaluate the anti-Parkinson’s activity of CERBO in the haloperidol- induced Parkinsonian rat model. Animals were categorized into six groups as control, disease control and treatment groups. Parkinson’s disease (PD)-like symptoms were induced by administration of haloperidol 1 mg/kg, intraperitoneally; CERBO treatment groups received 2.5, 5, and 7.5 mg/kg orally before the administration of haloperidol for 21 days. Neurobehavioral, biochemical, neurochemical, and histopathological studies along with gene expression analysis were performed at the completion of the study. CERBO markedly recover the motor and non-motor PD-like symptoms in treatment groups dose-dependently. The levels of antioxidant enzymes, such as catalase, superoxide dismutase, reduced glutathione, and glutathione peroxidase, increased, while malondialdehyde levels decreased dose-dependently in CERBO-treated groups. CERBO dose-dependent elevations were observed in neurotransmitters (dopamine, serotonin, and noradrenaline). PD-associated specific biomarker (α-synuclein) decreased dose-dependently with downregulation in messenger RNA expression of neuro-inflammatory mediators (interleukin α, interleukin 1β, and tumor necrosis factor-α). Histopathological studies revealed recovery in neuronal loss, formation of Lewy’s bodies, and neurofibrillary tangles in the treatment groups. It was concluded from the data that CERBO possessed good anti-Parkinson’s activity and could be a novel, safe, and effective remedy for the treatment of PD.

Modulation of rhizosphere microbial community and metabolites by bio-functionalized nanoscale silicon oxide alleviates cadmium-induced phytotoxicity in bayberry plants

Cadmium (Cd) is an extremely toxic heavy metal that can originate from industrial activities and accumulate in agricultural soils. This study investigates the potential of biologically synthesized silicon oxide nanoparticles (Bio-SiNPs) in alleviating Cd toxicity in bayberry plants. Bio-SiNPs were synthesized using the bacterial strain Chryseobacterium sp. RTN3 and thoroughly characterized using advanced techniques. A pot experiment results demonstrated that Cd stress substantially reduced leaves biomass, photosynthesis efficiency, antioxidant enzyme activity, and induced oxidative damage in bayberry (Myrica rubra) plants. However, Bio-SiNPs application at 200 mg kg−1 significantly enhanced plant biomass, chlorophyll content (26.4 %), net photosynthetic rate (8.6 %), antioxidant enzyme levels, and mitigated reactive oxygen species production under Cd stress. Bio-SiNPs modulated key stress-related phytohormones by increasing salicylic acid (13.2 %) and abscisic acid (13.7 %) contents in plants. Bio-SiNPs augmented Si deposition on root surfaces, preserving normal ultrastructure in leaf cells. Additionally, 16S rRNA gene sequencing demonstrated that Bio-SiNPs treatment favorably reshaped structure and abundance of specific bacterial groups (Proteobacteria, Actinobacteriota, and Acidobacteriota) in the rhizosphere. Notably, Bio-SiNPs application significantly modulated the key metabolites (phenylacetaldehyde, glycitein, maslinic acid and methylmalonic acid) under both normal and Cd stress conditions. Overall, this study highlights that bio-nanoremediation using Bio-SiNPs enhances tolerance to Cd stress in bayberry plants by beneficially modulating biochemical, microbial, and metabolic attributes.

Protective effects of astaxanthin on particulate matter 2.5‑induced senescence in HaCaT keratinocytes via maintenance of redox homeostasis.

Particulate matter 2.5 (PM2.5) imposes a heavy burden on the skin and respiratory system of human beings, causing side effects such as aging, inflammation and cancer. Astaxanthin (ATX) is a well-known antioxidant widely used for its anti-inflammatory and anti-aging properties. However, few studies have investigated the protective effects of ATX against PM2.5-induced senescence in HaCaT cells. In the present study, the levels of reactive oxygen species (ROS) and antioxidant enzymes were measured after treatment with PM2.5. The results revealed that PM2.5 generated excessive ROS and reduced the translocation of nuclear factor erythroid 2-related factor 2 (NRF2), subsequently reducing the expression of antioxidant enzymes. However, pretreatment with ATX reversed the ROS levels as well as the expression of antioxidant enzymes. In addition, ATX protected cells from PM2.5-induced DNA damage and rescued PM2.5-induced cell cycle arrest. The levels of senescence-associated phenotype markers, such as interleukin-1β, matrix metalloproteinases, and β-galactosidase, were increased by exposure to PM2.5, however these effects were reversed by ATX. After interfering with NRF2 mRNA expression and exposing cells to PM2.5, the levels of ROS and β-galactosidase were higher compared with siControl RNA cells exposed to PM2.5. However, ATX inhibited ROS and β-galactosidase levels in both the siControl RNA and the siNRF2 RNA groups. Thus, ATX protects HaCaT keratinocytes from PM2.5-induced senescence by partially inhibiting excessive ROS generation via the NRF2 signaling pathway.

Elucidation of the Role of TRPV1, VEGF-A, TXA2, Redox Homeostasis, and Inflammatory Cascades in Protection against Cold Injuries by Herbosomal-Loaded PEG-Poloxamer Topical Formulation.

High-altitude regions, cold deserts, permafrost regions, and the polar region have some of the severest cold conditions on earth and pose immense perils of cold injuries to exposed individuals. Accidental and unintended exposures to severe cold, either unintentionally or due to occupational risks, can greatly increase the risk of serious conditions including hypothermia, trench foot, and cold injuries like frostbite. Cold-induced vasoconstriction and intracellular/intravascular ice crystal formation lead to hypoxic conditions at the cellular level. The condition is exacerbated in individuals having inadequate and proper covering and layering, particularly when large area of the body are exposed to extremely cold environments. There is a paucity of preventive and therapeutic pharmacological modalities that have been explored for managing and treating cold injuries. Given this, an efficient modality that can potentiate the healing of frostbite was investigated by studying various complex pathophysiological changes that occur during severe cold injuries. In the current research, we report the effectiveness and healing properties of a standardized formulation, i.e., a herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF), on frostbite. The intricate mechanistic pathways modulated by the novel formulation have been elucidated by studying the pathophysiological sequelae that occur following severe cold exposures leading to frostbite. The results indicate that n-HPTF ameliorates the outcome of frostbite, as it activates positive sensory nerves widely distributed in the epidermis transient receptor potential vanilloid 1 (TRPV1), significantly (p < 0.05) upregulates cytokeratin-14, promotes angiogenesis (VEGF-A), prominently represses the expression of thromboxane formation (TXA2), and significantly (p < 0.05) restores levels of enzymatic (glutathione reductase, superoxide dismutase, and catalase) and nonenzymatic antioxidants (glutathione). Additionally, n-HPTF attenuates oxidative stress and the expression of inflammatory proteins PGF-2α, NFκB-p65, TNF-α, IL-6, IL-1β, malondialdehyde (MDA), advanced oxidative protein products (AOPP), and protein carbonylation (PCO). Masson's Trichrome staining showed that n-HPTF stimulates cellular proliferation, and increases collagen fiber deposition, which significantly (p < 0.05) promotes the healing of frostbitten tissue, as compared to control. We conclude that protection against severe cold injuries by n-HPTF is mediated via modulation of pathways involving TRPV1, VEGF-A, TXA2, redox homeostasis, and inflammatory cascades. The study is likely to have widespread implications for the prophylaxis and management of moderate-to-severe frostbite conditions.

Physiological response of chestnuts (Castanea mollissima Blume) infected by pathogenic fungi and their correlation with fruit decay

The postharvest decay of chestnuts (Castanea mollissima Blume) limits their industrial utilization, and pathogenic fungi are the main cause for chestnut decay. In this study, the physiological changes and their correlation with the rotting degree of chestnuts were investigated during single or mixed infection by Fusarium proliferatum, Penicillium crustosum, and Alternaria alternata. During the infection period, the activities of cell wall degrading enzymes (CWDEs) and antioxidant enzymes firstly increased and then decreased, the contents of nutrients decreased, but the levels of physiological indexes increased. The mycelium and spores of pathogenic fungi colonized the intercellular space, and then the mycelium covered the entire tissue surface of chestnuts, leading to the disappearance of cell structure. Notably, the most prominent changes in physiological indexes and ultrastructure were observed in chestnuts infected with three pathogenic fungi. Furthermore, the rotting degree of chestnuts was positively correlated with the levels of CWDEs, antioxidant enzymes and malondialdehyde.

Tert-butylhydroquinone prevents cyclophosphamide induce lung toxicity in rats via inhibiting oxidative stress and apoptosis: in vivo and in silico study

BackgroundCyclophosphamide (CP) is a chemotherapeutic and immunosuppressive agent that induces oxidative stress, causing lung tissue damage.AimThe study aims to explore the antioxidant role of tert-butylhydroquinone (TBHQ) in ameliorating CP-induced lung toxicity exhibited as oxidative stress and programmed cell death.MethodsThirty-two adult male rats were allocated randomly into four groups: group 1 (control), group 2 TBHQ 50 mg/kg orally for 14 days, and group 3 single dose of (200 mg/kg, CP, i.p.) on the 9th day. In group 4, TBHQ (50 mg/kg, orally) was provided for 14 days, and (200 mg/kg, CP, i.p.) was administrated on the 9th day. Rats’ body and lung weight were measured. Oxidative stress marker malondialdehyde (MDA) and pulmonary tissue enzymatic antioxidant levels were assessed: glutathione S transferase, catalase, superoxide dismutase, and glutathione peroxidase. Additionally, glutathione level was measured. Assessment of the levels of TNF-α, IL-1β, and IL-6 were done as well as histopathological and immunohistochemistry investigations. Molecular docking studies of the protein structures of p53-MDM2, IL-6, and IL-1β were performed.ResultsCP-intoxicated rats demonstrated a significant decline (CAT, GPx, SOD, GST, and GSH) levels and a significant increase in MDA levels. The proinflammatory parameters (TNF-α, IL-6, IL-1ß) were significantly elevated in group 3. The noted biochemical changes, accompanied by histopathological destruction, indicate CP-induced pulmonary tissue injury. TBHQ played a protective role by attenuating most of the aforementioned biochemical alterations and histopathological distortions in rats’ lungs.ConclusionsTBHQ might be utilized as a potential ameliorative agent to inhibit CP-induced pulmonary toxicity via TBHQ’s antioxidant and anti-inflammatory effects.

Anisomeles indica (L.) Kuntze leaf essential oil ameliorates LPS-induced inflammation in RAW 264.7 cells: An integrated approach of network pharmacology and experimental validation

Anisomeles indica (L.) Kuntze (Lamiaceae), commonly called catmint, is an essential oil-bearing herb used in traditional systems of medicine against rheumatism, convulsions, inflammatory skin disorders, and epilepsy. However, the efficacy and mechanism of action of its essential oil against inflammatory conditions remain elusive. The current study aims at the chemical characterization of the essential oil of A. indica leaves (AILEO) and understanding the mechanism of its anti-inflammatory effects by an integrated approach of network pharmacology and in vitro assays. GC–MS analysis of AILEO revealed a total of 30 constituents representing 94.19 % of the total oil. The majority of the chemical groups include diterpene hydrocarbons with abietatriene (58.13 %) and abietadiene (7.18 %) as the major constituents. Out of 30 compounds, 20 passed the ADME screening and were considered as active constituents. A total of 524 compound targets, 409 anti-inflammation targets, and 88 compound-disease intersecting targets were obtained. Multi-level network analysis revealed that the pharmacological mechanisms of alleviation of inflammation by AILEO are due to its interaction with five core inflammatory targets such as PI3K, AKT1, MEK1, ERK1, and RXRA involved in the PI3K-AKT signaling pathway. AILEO did not exhibit any cytotoxic effect on RAW 264.7 cells, but it significantly inhibited nitric oxide (NO) production and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in vitro assays. Further, AILEO enhanced the expression levels of endogenous antioxidant enzymes (CAT, SOD, GPx, and GSH) in comparison to the LPS-induced group. RT-qPCR analysis revealed that AILEO modulated the level of mRNA expression of all five core targets associated with the PI3K-AKT signaling pathway, which further supported the findings of network pharmacology. This study provides valuable insights into the intricate mechanisms by which AILEO exerts anti-inflammatory action indicating its pharmacological potential as a promising candidate for the treatment of disorders linked with inflammation.

Combined exposure of polystyrene microplastics and benzo[a]pyrene in rat: Study of the oxidative stress effects in the liver

Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on organisms. However, the combined effects and mechanisms of exposure in mammals remain unknown. Thus, this study aims to investigate the potential effects of oral administration of 0.5μm polystyrene (PS) MPs (1 mg/mL or 5 mg/mL), B[a]P (1 mg/mL or 5 mg/mL) and combined (1 mg/mL or 5 mg/mL) on 64 male SD rats by gavage method over 6-weeks. The results demonstrate that the liver histopathological examination showed that the liver lobules in the combined (5 mg/kg) group had blurred and loose boundaries, liver cord morphological disorders, and significant steatosis. The levels of AST, ALT, TC, and TG in the combined dose groups were significantly higher than those in the other groups, the combined (5 mg/kg) group had the lowest levels of antioxidant enzymes and the highest levels of oxidants. The expression of Nrf2 was lowest and the expression of P38, NF-κB, and TNF-α was highest in the combined (5 mg/kg) group. In conclusion, these findings indicate that the combination of PSMPs and B[a]P can cause the highest levels of oxidative stress and elicit markedly enhanced toxic effects, which cause severe liver damage.

Protective Effect of Prunetin on Isoproterenol-Induced Myocardial Infarction in Wistar Rats via Biochemical Characterization.

The development of MI following ischemia damage is influenced by oxidative stress. Myocardial Infarction (MI) generates myocardial ischemia injury, which damages the cardiomyocytes. Ischemia builds up to a critical level over time in MI, causing permanent myocardial cell damage or death. The current study sought to determine whether Prunetin (PRU) could protect against Isoproterenol (ISO)-induced cardiac heart failure in rats by examining cardiac diagnostic markers, lipid peroxidation products, enzymatic and non-enzymatic antioxidant levels, and histological changes. PRU (20 mg/kg bwt) was orally administered for 19 days to rats, and after the treatment, ISO (85 mg/kg bwt) was subcutaneously administered with an intermission of 24 h for a couple of days to induce myocardial infarction on 20th and 21st days. ISO-treated rats exhibited considerable alterations in cardiac-sensitive markers in the serum. The levels of lipid peroxidation markers augmented drastically in the plasma and myocardium. Enzymatic antioxidant levels in erythrocytes and myocardium and the states of non-enzymatic antioxidants were diminished in the plasma and heart tissue of ISO-treated rats. The histopathological examination of heart tissue exhibited cardiac damage in ISO-induced rats. The oral administration of PRU significantly lowered the levels of lipid peroxidation and biochemical indicators, while significantly improving the antioxidant system function of ISO-interposed rats. In PRU-treated ISO-injected rats, histological examinations revealed suppressed myocardial destruction. Our research shows that oral pretreatment of PRU prevented ISO-induced oxidative stress in MI.

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation. Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity. The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants. Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP.

Reducing the injury of hippocampal vascular endothelial cells after stroke via targeting SIRT1 by butylphthalide

Butylphthalide (NBP) can inhibit various pathological processes of ischemic stroke. This experiment explored the mechanism of NBP and SIRT1 on damage of hippocampal vascular endothelial cells after stroke. The neurons in the hippocampus of rats were stained with HE, and morphology and density of neurons were observed. Flow cytometry, commercial kits and Western blotting detected apoptosis of endothelial cells, levels of antioxidant enzymes and apoptotic proteins, intracellular calcium level and activity of Ca2+-ATPase. The damage to rat nerve cells was alleviated by butylphthalide to varying degrees, and the lost parts of rat nerve cells were recovered with decreased Bax and cleaved caspase-3 expression after butylphthalide treatment, and increased Bcl-2 (P &lt;0.05), as well as decreased serum malondialdehyde (MDA) content and activity of catalase (CAT) decreased and elevated Superoxide dismutase (SOD) activity (P &lt;0.05). The concentration of calcium ion also decreased but activity of Ca2+-ATPase increased (P &lt;0.05) and mitochondria in the model group appeared with severe vacuolation and swelling. The vacuolation and swelling of mitochondria in the treatment group were improved. Additionally, mitochondrial membrane fluidity, potential and rat hippocampal ATPase activity in butylphthalide group were also increased. Compared to normal control group, model group, SIRT1 inhibitor group and butylphthalide+SIRT1 inhibitor group had lower levels of SIRT1 and higher p-NF-kB p65/p-IkBα levels. Butylphthalide has a protective effect on hippocampal neurons in stroke rats and can alleviate the damage degree of rat nerve cells.

Microalgal Macular Pigment Alleviated the Pathogenic Process in the Streptozotocin-induced Diabetic ApoE-deficient Mice

Type 2 diabetes mellitus (T2DM) is one of the fastest growing epidemics in human history and characteristic is insulin resistance (IR), and endocrine disorder that promoted to decline in insulin production and inhibit cellular effects. Patients with T2DM would lead to many complications such as diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, diabetic foot, atherosclerosis, vascular inflammation, and hepatogenous diabetes due to hyperglycemia. Even after using medical treatment and lifestyle modifications, it is still hard to achieve the goal of reducing blood glucose to an optimal level. Microalga Chlorella sp., a unicellular green alga that has been used as a health food and nutritional product in the last few decades. Macular pigment (MP) produced by Chlorella sp. consists of rich lutein and zeaxanthin, which are regarded as the antioxidants to hyperglycemia-induced oxidative stress. MP is widely used in eye health care, however, few studies focused on scientifically exploring the protection mechanism of MP on diabetes mellitus. Therefore, this study aimed to explore MP extracted from Chlorella on reducing retinopathy and atherosclerosis damages in the diabetic apolipoprotein E deficient mice (ApoE−/−) with high-fat diet feeding and streptozotocin treatment. The results show that MP supplement could significantly reduce glucose tolerance, IR, inflammatory cytokines TNF-α and IL-6 levels, and the serum level of disease markers, i.e., triglyceride (TG), total cholesterol (TCHO), glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), total protein (TP), albumin (ALB), and blood urea nitrogen (BUN) in the diabetic ApoE−/− mice. In addition, the expression levels of cellular antioxidant enzymes were significantly increased and the adhesion factors as well as MAPK pathway proteins in renal tissues were significantly reduced after MP supplementation. The pathological changes of pancreatic islet morphology, hepatic lipid accumulation, outer nuclear layer and aortic plaque of the diabetic ApoE−/− mice were significantly alleviated by MP supplement. At present, most MP products are derived from marigold, Calendula offcinalis, in the market. However, microalgae cultivation includes the advantages on no seasonal limit, no competition, high yield and carbon reduction compared with other plants. In summary, the microalgal MP improved IR, ameliorated atherosclerosis, and alleviated retinopathy in the diabetic ApoE−/− mice. Consequently, the microalgal MP is potentially to be a healthy food ingredient for the biological effcacy of scavenging free radicals and stabilizing blood glucose. This work was supported by the grants of NSTC 110-2312-B-A49-001-MY3, NSTC 112-2811-B-A49 -501, NSTC 112-2811-B-A49 -503, NSTC 112-2321-B-A49 -018 and NSTC 112-2321-B-A49-005, from the National Science and Technology Council (NSTC), Taiwan. This work was also financially supported by the “Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B)” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project of the National Yang Ming Chiao Tung University and Ministry of Education (MOE), Taiwan. 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.

Comparison Of Transient ACE Inhibitor Vs. Angiotensin Receptor Blocker Treatment On Angiotensin II-Induced Oxidative Stress In The Heart Of Spontaneously Hypertensive Rats

Angiotensin II (Ang II) is a primary mediator of the renin angiotensin system (RAS) with strong profibrotic effects, mediated in part through increased levels of reactive oxygen species (ROS). We have previously shown that transient treatment with an Ang II converting enzyme inhibitor (ACEi) produces long-term protection against Ang II-induced fibrosis. Our goal was to compare the impact of prior transient AT1 receptor antagonist (ARB) vs. ACEi treatment on the oxidative stress response and fibrotic signaling profile in the left ventricle (LV) in response to Ang II. Male and female spontaneously hypertensive rats were initially treated with vehicle, ARB (losartan, 30mg/kg per day) or ACEi (enalapril, 30mg/kg per day) for two weeks. To assess long term protection of ARB and ACEi treatment, after two-weeks of washout, the rats then received Ang II (400ng/kg/day) for 2 additional weeks. Protein levels of pro-oxidant (NOX-2) and antioxidant (SOD1, SOD2) enzymes, fibrosis marker (LOX) in the left ventricle (LV) were measured by western blotting. Cardiac hypertrophy was evaluated by the LV mass/tibia Length (LV/TL) ratio. Data were analyzed by 2-way ANOVA. After a transient ARB treatment, Ang II promoted an increase in LV/TL in both male (+7%) and female (+9%) rats when compared to vehicle+Ang II (treatment effect, p&lt;0.009). Ang II had no effect on LV/TL in rats previously treated with ACEi or vehicle. In response to Ang II, male and female rats that were previously treated with ACEi showed a decrease in LOX expression (treatment effect, p=0.02) in both male (-21%) and female (-22%) rats. No changes were observed in LOX in response to Ang II after ARB treatment. In rats transiently treated with ARB or ACEi, the expression of NOX2 was reduced after Ang II infusion. In the ARB group the NOX2 was reduced 25% in male and 28% in female (treatment effect, P=0.003). Similarly, in the ACEi group, NOX2 was reduced 27% in male and 26% in female rats (treatment effect, p&lt;0.0001). Prior ACEi and ARB produced sex-selective changes in SOD1 expression following Ang II infusion. Specifically, following transient ARB treatment, Ang II increased SOD1 in females (24%), but not males (sex x ARB treatment interaction: p=0.0033). Similarly, prior treatment with ACEi produced sex-dependent effects, whereby AngII increased SOD1 in females (10%) and decreased expression in males (-8%, ACEi x sex interaction: p=0.043). Neither ARB, ACEi nor Ang II affected the expression of SOD2 Our data indicate a sex and treatment-specific response to Ang II following transient ARB or ACEi treatment. Both ARB and ACEi showed a long-term beneficial effect on oxidative stress. However, ARB appeared to sensitize males and females to a hypertrophy response to AngII. Future studies will evaluate this differential response observed in cardiac hypertrophy and the mechanisms leading to cardiac fibrosis. NHBL R01HL153112. 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.

Activation of the Nrf-2 pathway improves the mitochondrial phenotype in skeletal muscle cells

Aging muscle displays a reduction in mitochondrial content, along with elevated reactive oxygen species (ROS) emission and reduced levels of antioxidant enzymes. These characteristics enhance tissue susceptibility to oxidative damage, facilitating sub-optimal cellular metabolism and subsequent muscle atrophy. While these perturbations to metabolic homeostasis are a natural course of the aging process, there has been ongoing research investigating how to implement interventions to reduce this decline in muscle health. Regular exercise is one possible treatment modality, however this may be unsuitable for some populations who are unable to participate due to their health status. The objective of this study was to examine the activation of the Nrf-2 pathway using the nutraceutical Sulforaphane (SFN) and evaluate its role as a potential exercise mimetic. We hypothesized that SFN would act through similar pathways activated with chronic exercise to improve mitochondrial content, respiration, and ROS emission. To address our objective, C2C12 myotubes were treated with SFN for various timepoints basally, and in the presence of the Complex-I inhibitor rotenone to induce oxidative stress. Western blotting revealed an 8-fold increase in Nrf-2 nuclear localization following 24hrs of SFN treatment, which subsequently led to the upregulation of antioxidant enzymes NQO1, Heme Oxygenase-1, catalase, glutathione reductase and Glucose-6-Phosphate Dehydrogenase by 2-to 3-fold. These protein changes, were accompanied by dramatic reductions in both total cellular and mitochondrial ROS emission with SFN, detected with CellROX Green and MitoSOX Red respectively. Interestingly, this led to an increase in mitochondrial membrane potential, detected via MitoTracker Red (MTR), despite rotenone-induced oxidative stress. Western blotting revealed TFAM upregulation at 24hrs, suggesting an increase in mitochondrial DNA (mtDNA) replication and transcription. This was corroborated by an increase in COX subunit I protein, a mitochondrially-encoded subunit of cytochrome c oxidase, as well as MitoTracker Green and MTR staining by 48hrs. Mitochondrial respiration was evaluated using Seahorse analysis, demonstrating a marked increase in ATP production as well as basal and maximal respiration. Together these data suggest that activation of the Nrf-2 pathway via SFN may lead to adaptations similar to chronic exercise. Additionally, SFN may have applications in disorders characterized by mitochondrial loss and high ROS emission. To fully elucidate the precise mechanisms underlying this agent, SFN will be combined with chronic contractile activity to determine if these two interventions operate through independent pathways. This work was supported by funds from the Natural Science and Engineering Research Council (NSERC). Sabrina Champsi is the recipient of the NSERC Alexander Graham Bell Canada Graduate Scholarship-Master’s (CGS-M). David A. Hood is the holder of a Canadian Research Chair in Cell Physiology. 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.

Dietary chamomile flowers extract improved performance and mitigated aflatoxin B1 toxicity in rabbits.

Aflatoxin B1 (AFB1) is among the poisonous mycotoxins that contaminate food and feed. Limited studies are available on the efficacy of chamomile (Cha) against oxidative stress, liver damage and pro-inflammatory response induced by AFB1. The present study aims to evaluate the effects of Cha on the performance and protective effects against AFB1 in growing rabbits. The experimental rabbits were divided into four different groups, including Cha (70 mg kg day-1), AFB1 (AF; 30 μg kg day-1), AFB1+Cha (AFLCha) and control (CON). The results indicated that the AFB1 treatment had lower values of performance, and carcass parameters compared to the Cha and AFLCha treatments. Furthermore, the Cha and AFLCha groups had lower values of liver and kidney function activities compared to the AFB1 treatment. The higher values of antioxidant enzymes were observed in Cha and AFLCha treatments than in the AFB1 treatment. AFB1 treatments had higher levels of malondialdehyde and liver functions with lower levels of antioxidant enzymes (glutathione and superoxide dismutase) compared to Cha and CON groups. In conclusion, dietary Cha could mitigate the oxidative stress of AFB1-induced liver deterioration.