Antioxidant Superoxide Dismutase Research Articles

Attenuation of chromium (VI) and arsenic (III)-induced oxidative stress and hepatic apoptosis by phloretin, biochanin-A, and coenzyme Q10 via activation of SIRT1/Nrf2/HO-1/NQO1 signaling.

Heavy metal contamination is an alarming concern on a global scale, as drinking tainted water significantly increases human susceptibility to heavy metals. In a realistic scenario, humans are often exposed to a combination of harmful chemicals rather than a single toxicant. Phloretin (PHL), biochanin-A (BCA), and coenzyme Q10 (CoQ10) are bioactive compounds owning plentiful pharmacological properties. Henceforth, the current research explored the putative energizing effects of selected nutraceuticals in combined chromium (Cr) and arsenic (As) intoxicated Swiss albino mice. Potassium dichromate (75 ppm) and sodium meta-arsenite (100 ppm) were given in the drinking water to induce hepatotoxicity, conjugated with PHL and BCA (50 mg/kg each), and CoQ10 (10 mg/kg) intraperitoneally for 2 weeks. After the statistical evaluation, it was observed that the hepato-somatic index, metal load, and antioxidant activity (lipid peroxidation and protein carbonyl content) increased along with the concomitant decrease in the antioxidants (catalase, glutathione-S-transferase, superoxide dismutase, reduced glutathione, and total thiol) in the Cr and As intoxicated mice. Additionally, light microscopy observations, DNA breakages, decreased silent information regulator 1 (SIRT1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) gene expressions, together with stimulated apoptotic cell death manifested by the increased expressions of caspase 8 and caspase 3, thus, proved consistency with the aforementioned outcomes. Importantly, the treatment with nutraceuticals not only restored the antioxidant activity but also favorably altered the expressions of SIRT1, Nrf2, HO-1, and NQO1 signaling and apoptosis markers. These findings highlight the crucial role of the PHL, BCA, and CoQ10 combination in reducing Cr and As-induced hepatotoxicity in mice. By averting the triggered apoptosis in conjunction with oxidative stress, this combination increases the SIRT1, Nrf2, HO-1, and NQO1 signaling, thereby reassuringly maintaining the cellular equilibrium.

Consumption effect comparison of transgenic and non-transgenic soybean flour on antioxidant superoxide dismutase and spermatogenic cells profile of experimental rats

Consumption effect comparison of transgenic and non-transgenic soybean flour on antioxidant superoxide dismutase and spermatogenic cells profile of experimental rats

Total Antioxidant Capacity, Salivary Catalase, and Superoxide Dismutase in Hashimoto's Thyroiditis Patients

Total Antioxidant Capacity, Salivary Catalase, and Superoxide Dismutase in Hashimoto's Thyroiditis Patients

The Eliciting Effect of Aqueous Extracts from Ascophyllum nodosum Algae on the Cultivation of Arugula (Eruca sativa Mill.) Microgreens

This study showed the eliciting effect of aqueous extracts from Ascophyllum nodosum on the development of Eruca sativa microgreens in a quartz-based substrate. There is no information in the literature on the impact of its use on the quality, bioactive compound content, and nutritional value of arugula microgreens. Assays that have been made include the following: total phenolic content (TPC), total flavonoid content (TFV), enzymes such as phenylalanine ammonia (PAL) and polyphenol oxidase (PPO), and enzymes involved in the scavenging of reactive oxygen species such as catalase (CAT) and superoxide dismutase (SOD). The antioxidant activity against DPPH (2,2-diphenyl-1-picrylhydrazyl) was also evaluated. The total phenolic content of arugula microgreens increased significantly after an application of aqueous extracts of A. nodosum to the substrate. The greatest increase in flavonoid content (89%) and antioxidant activity against DPPH (82%) was observed at a concentration of 2.5%. The highest increase in activity of CAT (68.2%), SOD (25%), PAL (13-fold), and PPO (84.2%) was observed with the application of 5% extract. In conclusion, the use of Ascophyllum nodosum algae affects TPC and TFV, antioxidant activity, PAL, PPO, SOD, and CAT in the microgreens studied. By prioritising organic and environmentally friendly extracts, growers can contribute to a more sustainable and healthier food system, especially in the case of the production of Eruca sativa microgreens.

Acetyl-l-carnitine alleviates valproate-induced autism-like behaviors through attenuation of hippocampal mitochondrial dysregulation

This study aimed to evaluate the potential benefits of acetyl-L-carnitine (ALCAR) in the context of valproate-induced autism. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p.) on embryonic day 12.5, followed by ALCAR treatment (300 mg/kg on postnatal days 21–49, p.o.), assessment of oxidative stress, mitochondrial membrane potential (MMP), mitochondrial biogenesis, parvalbumin interneurons, and hippocampal volume was conducted. These assessments were carried out subsequent to the evaluation of autism-like behaviors. Hippocampal analysis of oxidative factors (reactive oxygen species and malondialdehyde) and antioxidants (superoxide dismutase, catalase, and glutathione) revealed a burden of oxidative stress in VPA rats. Additionally, mitochondrial biogenesis and MMP were elevated, while the number of parvalbumin interneurons decreased. These changes were accompanied by autism-like behaviors observed in the three-chamber maze, marble burring test, and Y-maze, as well as a learning deficit in the Barnes maze. In contrast, administrating ALCAR attenuated behavioral deficits, reduced oxidative stress, improved parvalbumin-positive neuronal population, and properly modified MMP and mitochondrial biogenesis. Collectively, our results indicate that oral administration of ALCAR ameliorates autism-like behaviors, partly through its targeting oxidative stress and mitochondrial biogenesis. This suggests that ALCAR may have potential benefits ASD managing.

Expression of Foxtail Millet bZIP Transcription Factor SibZIP67 Enhances Drought Tolerance in Arabidopsis.

Foxtail millet is a drought-tolerant cereal and forage crop. The basic leucine zipper (bZIP) gene family plays important roles in regulating plant development and responding to stresses. However, the roles of bZIP genes in foxtail millet remain largely uninvestigated. In this study, 92 members of the bZIP transcription factors were identified in foxtail millet and clustered into ten clades. The expression levels of four SibZIP genes (SibZIP11, SibZIP12, SibZIP41, and SibZIP67) were significantly induced after PEG treatment, and SibZIP67 was chosen for further analysis. The studies showed that ectopic overexpression of SibZIP67 in Arabidopsis enhanced the plant drought tolerance. Detached leaves of SibZIP67 overexpressing plants had lower leaf water loss rates than those of wild-type plants. SibZIP67 overexpressing plants improved survival rates under drought conditions compared to wild-type plants. Additionally, overexpressing SibZIP67 in plants displayed reduced malondialdehyde (MDA) levels and enhanced activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) under drought stress. Furthermore, the drought-related genes, such as AtRD29A, AtRD22, AtNCED3, AtABF3, AtABI1, and AtABI5, were found to be regulated in SibZIP67 transgenic plants than in wild-type Arabidopsis under drought conditions. These data suggested that SibZIP67 conferred drought tolerance in transgenic Arabidopsis by regulating antioxidant enzyme activities and the expression of stress-related genes. The study reveals that SibZIP67 plays a beneficial role in drought response in plants, offering a valuable genetic resource for agricultural improvement in arid environments.

FeONPs alleviate cadmium toxicity in Solanum melongena through improved morpho-anatomical and physiological attributes, along with oxidative stress and antioxidant defense regulations

In this study, various constraints of Cd toxicity on growth, morpho-anatomical characters along with physiological and biochemical metabolic processes of Solanum melongena L. plants were analyzed. Conversely, ameliorative role of iron oxide nanoparticles (FeONPs) was examined against Cd stress. For this purpose, the following treatments were applied in completely randomized fashion; 3 mM CdCl2 solution applied with irrigation water, 40 and 80 ppm solutions of FeONPs applied via foliar spray. Regarding the results, Cd caused oxidative damage to plants’ photosynthetic machinery, resulting in elevated levels of stress-markers like malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolytic leakage (EL) along with slight increase in antioxidants activities, including glutathione (GsH), ascorbate (AsA), catalases (CAT), peroxidases (POD), superoxide dismutase (SOD), and ascorbate peroxidases (APX). Also, high Cd level in plants disturb ions homeostasis and reduced essential minerals uptake, including Ca and K. This ultimately reduced growth and development of S. melongena plants. In contrast, FeONPs supplementations improved antioxidants (enzymatic and non-enzymatic) defenses which in turn limited ROS generation and lowered the oxidative damage to photosynthetic machinery. Furthermore, it maintained ionic balance resulting in enhanced uptake of Ca and K nutrients which are necessary for photosynthesis, hence also improved photosynthesis rate of S. melongena plants. Overall, FeONPs foliar spray effectively mitigated Cd toxicity imposed on S. melongena plants.

Dietary Nannochloropsis oculata could ameliorate cadmium chloride-induced reproductive toxicity in Barki rams: Antioxidant, MAP3K8, and inflammatory pathways

The experiment was intended to explore the protecting effects of Nannochloropsis oculate on the induced cadmium reproductive toxicity in rams. Twenty mature Barki rams were randomly allocated into four groups, each containing five rams: group I (control), group II (received 3 % dietary N. oculate), group III (received 1 mg/Kg/day cadmium chloride (CdCl2), and group IV (received 3 % dietary N. oculate and 1 mg/Kg/day CdCl2). Semen ejaculates and blood samples were collected. Testicular volume and reaction time were assessed with every semen collection. Ejaculates were analyzed for semen criteria. Rams were subjected to a castration process to analyze the anti-oxidative status, including total antioxidant capacity (TAC) and superoxide dismutase (SOD), and inflammatory markers in the testicular homogenate. Testicular histopathology was performed on testicular sections. Gene expression of p38 Mitogen-Activated Protein Kinase (MAPK) was assessed. Alga-treated rams revealed significant improvement in semen criteria, testicular weight, and testosterone hormone as compared to other groups. The levels of testicular antioxidant markers and interleukin-10 elevated significantly in the alga group, while interleukin-12 increased in the CdCl2 group. Alga+CdCl2 rams showed significant amelioration in the previous parameters equated to the CdCl2 group. CdCl2 rams exhibited a significant fold upgrade in MAPK of compared with other groups. Testicular histopathology revealed marked alterations in the testicular architecture of CdCl2, while administration of alga recovered the testicular architecture. In conclusion, administration of N. oculate ameliorated semen criteria, testicular antioxidant capacity as well as testicular histopathology that was declared by the expression of MAPK38.

Electroacupuncture improves retinal function in myopia Guinea pigs probably via inhibition of the RhoA/ROCK2 signaling pathway

ObjectiveTo investigate the effect of electroacupuncture (EA) on retinal function in guinea pigs with negative lens-induced myopia (LIM) by inhibiting the RhoA/ROCK2 signaling pathway. MethodsGuinea pigs were randomly divided into normal control (NC) group, LIM group, EA group, SHAM acupoint (SHAM) group, and electro-acupuncture + ROCK pathway inhibitor Y27632 (EA + Y27632) group. The refraction, axial length, retinal blood flow density, choroidal vascular index, retinal physiological function, the contents of total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) of each group were determined. The changes in retinal tissue structure were observed by hematoxylin and eosin (H&E) staining, and the expression of the RhoA/ROCK2 signaling pathway-related molecules in the retina was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. ResultsMyopic refraction, AL, and MDA content in the LIM and SHAM groups were significantly increased, retinal blood flow density and CVI, SOD, GSH, CAT, T-AOC content were decreased. After EA intervention, myopic refraction, AL, and MDA content decreased, retinal blood flow density and CVI, SOD, GSH, CAT, T-AOC content were increased. H&E staining showed that the thickness of the guinea pig retina, the thickness of the inner and outer layers of the nucleus, and the number of cells were significantly increased after EA intervention. qPCR and western blot analyses showed that the expression of RhoA、ROCK2、MLC、CollagenⅠ、MMP-2、TIMP-2 and α-SMA were elevated in the LIM and SHAM group than those in the NC group. Compared with the LIM group, the expression of EA group was significantly decreased. ConclusionsElectroacupuncture can improve retinal function by improving retinal blood flow, reducing retinal oxidative damage, inhibiting RhoA/ROCK2 signaling pathway and controlling extracellular matrix remodeling, thus delaying the occurrence and development of myopia.

Replacing soybean meal with fermented rapeseed meal in diets: potential effects on growth performance, antioxidant capacity, and liver and intestinal health of juvenile tilapia (Oreochromis niloticus).

This study aims to evaluate the effects of substituting soybean meal with fermented rapeseed meal (FRM) on growth, antioxidant capacity, and liver and intestinal health of the genetically improved farmed tilapia (GIFT, Oreochromis niloticus). A total of 450 tilapia (7.22 ± 0.15g) were fed with five experimental diets, including a basal diet containing 40% soybean meal (CP0), which was subsequently replaced by 25% (CP25), 50% (CP50), 75% (CP75), and 100% (CP100) FRM in a recirculated aquiculture system for 9weeks (30 fish per tank in triplicates). The results showed that the weight gain, specific growth rate, feed intake, feed efficiency, hepatosomatic index, and viscerosomatic index of fish in both CP75 and CP100 groups were significantly lower than those in CP0 group (P < 0.05). The fish in CP100 group had the lower content of muscle crude protein while the higher level of muscle crude lipid (P < 0.05). Activities of serum aspartate aminotransferase, alanine aminotransferase along with total triglyceride in CP100 group were significantly higher than those in CP0 group (P < 0.05). There were no significant differences in the contents of liver protease, amylase, and lipase among five groups (P > 0.05). The activities of liver total antioxidant capacity and superoxide dismutase exhibited the increased tendency with the increase of FRM replacement levels from 25 to 50% (P < 0.05), while then significantly decreased from 75 to 100% (P < 0.05). Histological morphology indicated that the fish in between CP75 and CP100 groups had poor liver and intestine health. Intestinal microbial diversity analysis showed that the relative abundance of Cetobacterium and Alcaligenaceae in both CP75 and CP100 groups were lower than that in other three groups. In conclusion, the maximum replacement level of soybean meal with FRM in the diet was determined to be 50% without compromising the growth performance, antioxidant status, and liver and intestinal health of tilapia under the current experimental conditions. The observed decrease in food intake and subsequent retarded growth performance in the CP75 and CP100 groups can be attributed directly to a reduction in feed palatability caused by FRM.

Deacetylation mimetic mutation of mitochondrial SOD2 attenuates ANG II-induced hypertension by protecting against oxidative stress and inflammation.

Almost one-half of adults have hypertension, and blood pressure is poorly controlled in a third of patients despite the use of multiple drugs, likely because of mechanisms that are not affected by current treatments. Hypertension is linked to oxidative stress; however, common antioxidants are ineffective. Hypertension is associated with inactivation of key intrinsic mitochondrial antioxidant, superoxide dismutase 2 (SOD2), due to hyperacetylation, but the role of specific SOD2 lysine residues has not been defined. Hypertension is associated with SOD2 acetylation at lysine 68, and we suggested that deacetylation mimetic mutation of K68 to arginine in SOD2 inhibits vascular oxidative stress and attenuates hypertension. To test this hypothesis, we have developed a new deacetylation mimetic SOD2-K68R mice. We performed in vivo studies in SOD2-K68R mice using angiotensin II (ANG II) model of vascular dysfunction and hypertension. ANG II infusion in wild-type mice induced vascular inflammation and oxidative stress and increased blood pressure to 160 mmHg. SOD2-K68R mutation completely prevented increase in mitochondrial superoxide, abrogated vascular oxidative stress, preserved endothelial nitric oxide production, protected vasorelaxation, and attenuated ANG II-induced hypertension. ANG II and cytokines contribute to vascular oxidative stress and hypertension. Treatment of wild-type aortas with ANG II and cytokines in organoid culture increased mitochondrial superoxide twofold, which was completely prevented in aortas isolated from SOD2-K68R mice. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and pathogenesis of hypertension. We conclude that strategies to reduce SOD2 acetylation may have therapeutic potential in the treatment of vascular dysfunction and hypertension.NEW & NOTEWORTHY Essential hypertension is associated with hyperacetylation of key mitochondrial antioxidant SOD2; however, the pathophysiological role of SOD2 acetylation has not been defined. Our animal study of angiotensin II hypertension model shows that deacetylation mimetic SOD2-K68R mutation prevents pathogenic increase in vascular mitochondrial superoxide, abrogates vascular oxidative stress, preserves endothelial nitric oxide, protects endothelial-dependent vasorelaxation, and attenuates hypertension. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and the pathogenesis of hypertension.

Dibenzazepine, a γ-Secretase Enzyme Inhibitor, Protects Against Doxorubicin-Induced Cardiotoxicity by Suppressing NF-κB, iNOS, and Hes1/Hey1 Expression.

Doxorubicin (DOX) is an effective chemotherapeutic drug; however, its cardiotoxicity and resistance compromise its therapeutic index. The Notch pathway was reported to contribute to DOX cancer resistance. The role of Notch pathway in DOX cardiotoxicity has not been identified yet. Notch receptors are characterized by their extracellular (NECD) and intracellular(NICD) domains (NICD). The γ-secretase enzyme helps in the release of NICD. Dibenzazepine (DBZ) is a γ-secretase inhibitor. The present study investigated the effect of Notch pathway inhibition on DOX cardiotoxicity. Twenty-four male Wistar rats were divided into four groups: control group, DOX group, acute cardiotoxicity was induced by a single dose of DOX (20 mg/kg) i.p., DOX (20 mg/kg) plus DBZ group, and DBZ group. The third and fourth groups received i.p. injection of DBZ daily for 14 days at 2 mg/kg dose. DOX cardiotoxicity increased the level of serum creatine kinase-MB and cardiac troponin I, and it was confirmed by the histopathological examination. Moreover, the antioxidants glutathione peroxidase and superoxide dismutase levels were markedly decreased, and the inflammatory markers, inducible nitric oxide synthase, nuclear factor-ķB, and tumor necrosis factor-α were markedly increased. Furthermore, DOX increased BAX protein and downregulated BCL-2. In addition, DOX upregulated Notch pathway-related parameters: Hes1 and Hey1 mRNA levels, and increased Hes1 protein levels. DBZ ameliorated DOX-induced cardiotoxicity, evidenced by reducing the cardiac injury biomarkers, improving cardiac histopathological changes, correcting antioxidant levels, and reducing inflammatory and apoptotic proteins. Our study indicates the protective effect of Notch inhibitor against DOX-induced cardiotoxicity.

Naringin Prevents Diabetic-Induced Dysmetabolism in Male Wistar Rats by Modulating GSK-3 Activities and Oxidative Stress-Dependent Pathways.

Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and glucose dysmetabolism, is a major metabolic disorder accompanied with health and financial burden. Recently, research findings showed that orange peel extract (OPE) has health benefits such as improved insulin sensitivity and glucose metabolism. The present study aimed at establishing the role of naringin from OPE on T2DM-induced glucose and lipid dysmetabolism. Thirty male (30) Wistar rats were randomized into five groups: control, diabetes, diabetes + naringin, diabetes + orange peel, and diabetes + metformin. Oral administration was once per day for 28 days. After 28 days of treatment, naringin ameliorated the diabetes-induced increase in blood sugar, homeostatic model assessment (HOMA) IR, triglyceride, total cholesterol, triglyceride/high density lipoprotein, total cholesterol/high density lipoprotein, triglyceride glucose index, glucose synthase kinase-3, lactate, lactate dehydrogenase, malondialdehyde, c-reactive protein, and tumor necrosis factor α compared with the diabetic untreated animals. Furthermore, naringin reversed diabetes-induced decrease in serum insulin, HOMA B, HOMA S, quantitative insulin-sensitivity check index, high-density lipoprotein, total antioxidant capacity, superoxide dismutase, catalase, glucose transporter-4, and hepatic glycogen. This study showed that naringin prevented diabetes-induced dysglycemia and dyslipidemia via glucose synthase kinase-3 and oxidative stress-dependent pathways.

Adequate water supply enhances seedling growth and metabolism in Festuca kryloviana: insights from physiological and transcriptomic analys

BackgroundFestuca kryloviana is a significant native grass species in the Qinghai Lake region, and its low emergence rate is a primary factor limiting the successful establishment of cultivated grasslands. The region’s arid and low-rainfall climate characteristics result in reduced soil moisture content at the surface. Despite the recognized impact of water availability on plant growth, the specific role of moisture in seedling development remains not fully elucidated. This study aims to investigate the germination rate and seedling growth velocity of F. kryloviana seeds under varying moisture conditions, and to integrate physiological and transcriptomic analyses of seedlings under these conditions to reveal the mechanisms by which water influences seedling development.ResultsThe emergence rate of F. kryloviana seedlings exhibited an initial increase followed by a decrease with increasing moisture content. The highest emergence rate, reaching 75%, was observed under 20% soil moisture conditions. By the eighth day of the experiment, the lengths of the plumules and radicles under the optimal emergence rate (full water, FW) were 21.82% and 10.87% longer, respectively, than those under closely matching the soil moisture content during the background survey (stress water, SW). The differential development of seedlings under varying moisture regimes is attributed to sugar metabolism within the seeds and the accumulation of abscisic acid (ABA). At FW conditions, enhanced sugar metabolism, which generates more energy for seedling development, is facilitated by higher activities of α-amylase, sucrose synthase, and trehalose-6-phosphate synthase compared to SW conditions. This is reflected at the transcriptomic level with upregulated expression of the α-amylase (AMY2) gene and trehalose-6-phosphate synthase (TPS6), while genes associated with ABA signaling and transduction are downregulated. Additionally, under FW conditions, the expression of genes related to the chloroplast thylakoid photosystems, such as photosystem II (PSII) and photosystem I (PSI), is upregulated, enhancing the seedlings’ light-capturing ability and photosynthetic efficiency, thereby improving their autotrophic capacity. Furthermore, FW treatment enhances the expression of the non-enzymatic antioxidant system, promoting metabolism within the seeds. In contrast, SW treatment increases the activity of the enzymatic antioxidant system, including peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), to cope with water stress.ConclusionsOur experiment systematically evaluated the impact of moisture conditions on the growth and development of F. kryloviana seedlings. Physiological and transcriptomic data collectively indicate that adequate water (20%) supply enhances seedling growth and development by reducing ABA levels and increasing α-amylase activity within seeds, thereby boosting sugar metabolism and promoting the growth of seedling, which in turn leads to an improved emergence rate. Considering water management in future cultivation practices may be a crucial strategy for enhancing the successful establishment of F. kryloviana in grassland ecosystems.

Dihydromyricetin Inhibits Ferroptosis to Attenuate Cisplatin-Induced Muscle Atrophy.

Cisplatin is a widely used chemotherapy drug for the treatment of various cancers. However, although cisplatin is effective in targeting cancer cells, it has severe side effects including skeletal muscle atrophy. In this study, we aimed to characterize the role of Dihydromyricetin in cisplatin-induced muscle atrophy in mice. 5-week-old male C57BL/6 mice were treated with Dihydromyricetin for 14 days orally followed by in intraperitoneally cisplatin administration for 6 days. Gastrocnemius muscles were isolated for the following experiments. Antioxidative stress were determined by peroxidative product malondialdehyde (MDA) and antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Quadriceps muscle mass and grip strength were significantly restored by Dihydromyricetin in a dose-dependent manner. Moreover, muscle fibers were improved in Dihydromyricetin treated group. Excessive skeletal muscle E3 ubiquitin-protein ligases in cisplatin group were significantly repressed by Dihydromyricetin treatment. Dihydromyricetin significantly reduced oxidative stress induced by cisplatin by decreasing MDA level and restored SOD and GPx activities. In addition, ferroptosis was significantly reduced by Dihydromyricetin characterized by reduced iron level and ferritin heavy chain 1 and improved Gpx4 level. The present study demonstrated that Dihydromyricetin attenuated cisplatin-induced muscle atrophy by reducing skeletal muscle E3 ubiquitin-protein ligases, oxidative stress, and ferroptosis.

Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies.

Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE). The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses. AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity. The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.

Toxicological insight of metiram: immuno-oxidative, neuro-behavioral, and hemato-biochemical changes during acute exposure of Nile tilapia (Oreochromis niloticus)

BackgroundThe inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture.ObjectiveThis study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system.MethodsThree hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish’s behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET’s impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored.ResultsThe lethal concentration (LC50) of MET estimated using Finney’s probit technique was 3.77 mg/L. The fish’s behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5–7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5–7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure.ConclusionAccording to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated.

Pterostilbene alleviates MPTP-induced neurotoxicity by targeting neuroinflammation and oxidative stress

Pterostilbene (PTE), a naturally occurring phenolic compound primarily found in blueberries, demonstrates neuroprotective properties. However, the role of PTE in Parkinson's disease (PD) remains unclear. This study aimed to investigate the neuroprotective role of PTE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Our findings demonstrate that administering PTE effectively reversed the diminished levels of dopamine in the striatum, thereby ameliorating motor impairments in the MPTP model. Moreover, PTE administration mitigated the loss of dopaminergic (DA) neurons and reduced the upregulation of α-synuclein (α-syn) induced by MPTP. Mechanistic analysis revealed that PTE administration inhibited the activation of microglia and astrocytes, as well as pro-inflammatory factors such as TNF-α and IL-1β in the MPTP model. Additionally, PTE administration decreased MPTP-induced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing total antioxidant capacity (TAOC) and superoxide dismutase (SOD) activity, thereby attenuating oxidative stress. Collectively, these findings demonstrate that PTE exerts neuroprotective effects in the MPTP mouse model of PD by suppressing neuroinflammation and oxidative stress. Thus, PTE holds promise as a therapeutic agent for PD.

The transcription factor MhZAT10 enhances antioxidant capacity by directly activating the antioxidant genes MhMSD1, MhAPX3a and MhCAT1 in apple rootstock SH6 (Malus honanensis × M. domestica).

Stress tolerance in apple (Malus domestica) can be improved by grafting to a stress-tolerant rootstock, such as 'SH6' (Malus honanensis × M. domestica 'Ralls Genet'). However, the mechanisms of stress tolerance in this rootstock are unclear. In Arabidopsis (Arabidopsis thaliana), the transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 is a key component of plant tolerance to multiple abiotic stresses and positively regulates antioxidant enzymes. However, how reactive oxygen species are eliminated upon activation of ZINC FINGER OF ARABIDOPSIS THALIANA 10 in response to abiotic stress remains elusive. Here, we report that MhZAT10 in the rootstock SH6 directly activates the transcription of three genes encoding the antioxidant enzymes MANGANESE SUPEROXIDE DISMUTASE 1 (MhMSD1), ASCORBATE PEROXIDASE 3A (MhAPX3a) and CATALASE 1 (MhCAT1) by binding to their promoters. Heterologous expression in Arabidopsis protoplasts showed that MhMSD1, MhAPX3a and MhCAT1 localize in multiple subcellular compartments. Overexpressing MhMSD1, MhAPX3a or MhCAT1 in SH6 fruit calli resulted in higher superoxide dismutase, ascorbate peroxidase and catalase enzyme activities in their respective overexpressing calli than in those overexpressing MhZAT10. Notably, the calli overexpressing MhZAT10 exhibited better growth and lower reactive oxygen species levels under simulated osmotic stress. Apple SH6 plants overexpressing MhZAT10 in their roots via Agrobacterium rhizogenes-mediated transformation also showed enhanced tolerance to osmotic stress, with higher leaf photosynthetic capacity, relative water content in roots and antioxidant enzyme activity, as well as less reactive oxygen species accumulation. Overall, our study demonstrates that the transcription factor MhZAT10 synergistically regulates the transcription of multiple antioxidant-related genes and elevates reactive oxygen species detoxification.

Enhancing the nutritional value and antioxidant properties of foxtail millet by solid‐state fermentation with edible fungi

AbstractFoxtail millet is typically dehulled before consumption or processing. However, foxtail millet bran also contains abundant phenolic compounds and other nutrients. Edible fungi have rich extracellular enzyme systems; are environmentally friendly and safe for consumption; and have been shown to effectively degrade lignin and cellulose. This study aimed to screen edible fungi that can effectively ferment undehusked foxtail millet, improving its nutritional value and antioxidant properties through solid‐state fermentation (SSF). The results demonstrated that fermentation utilizing Pleurotus geesteranus exhibited significant improvements in both the phenolic compound content and antioxidant properties of foxtail millet, with the optimal fermentation period determined to be 30 days. The physical and functional properties of fermented undehusked foxtail millet (FFM) flour were effectively improved, increasing crude protein, vitamin C, and crude polysaccharide contents by 11.46%, 27.78%, and 54.17%, respectively. In vitro scavenging activities of FFM were 73.19%, 93.86%, and 63.75% for 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS·+), and superoxide anion radicals (O2−), respectively. The total antioxidant capability (T‐AOC) and superoxide dismutase (SOD) activity of FFM were 1.01 mM Trolox equivalents (TE)/g and 89.05 U/g, respectively. Additionally, T‐AOC, SOD, and glutathione peroxidase (GSH‐Px) activities increased, whereas malondialdehyde (MDA) levels decreased in the heart, liver, and kidneys of mice treated with FFM flour, indicating enhanced antioxidant capacity. Therefore, fermentation with edible fungi is suitable for improving the nutritional composition and antioxidant properties of foxtail millet.