Increased Superoxide Dismutase Activity Research Articles

Exploring the Anti-Cancer Properties of Pomegranate Peel Aqueous Extract

The objective of this work is to evaluate the influence of pomegranate peel extract (PPE) in the behavior of breast cell lines (epithelial and tumor type) and related oxidative metabolism. Fruit-based functional foods have been the target of increasing scientific research for their physiological and pathophysiological properties. Pomegranate (Punica granatum) is a suitable example with both prophylactic and medicinal effects. MCF-7 cell line from tumor breast carcinoma, and MCF-10A cell line from normal epithelial mammary gland were used and subjected to different concentrations of PPE, ranging from 1 to 5 mM of gallic acid equivalents (GAE). Viability, proliferation, mobility, and cytotoxicity assays were performed along with the quantification of antioxidant enzymes, namely, catalase, superoxide dismutase (SOD) and reduced (GSH) and oxidized (GSSG) glutathione. We observed a decrease in viability and proliferation of MCF-7 cells, at higher concentrations of PPE, with no influence in epithelial cells. Interestingly, in a concentration-dependent manner, PPE triggered a significant decrease in migration on both cell lines, with a more pronounced effect in breast cancer cell line. Regarding antioxidant enzyme activity, on tumor cells higher concentrations of PPE decreased catalase activity and significantly increased SOD activity. Regarding GSH and GSSG, we observed different expression levels between MCF-7 and MCF-10A, with MCF-7 presenting lower levels compared to MCF-10A. GSH/GSSG ratio was notably higher in MCF-7 at 5 mM GAE. PPE exhibits anti-tumor effects without significantly affecting normal epithelial cells. Our work strengthens the potential antitumoral effect of PPE by reducing MCF-7 cell viability and proliferation through the imbalance of antioxidant enzymes.

Supplementation with grape seed extract, onion peel extract, or rosemary extract in the diet alleviates growth inhibition, liver damage, and oxidative stress induced by diquat in Lohmann chicks

The present study aimed to assess the impact of grape seed extract (GSE), onion peel extract (OPE), and rosemary extract (ROE) on Diquat-induced growth restriction and oxidative stress in Lohmann chicks. A total of 200 chicks were randomly assigned to 5 diets: the positive control (PC) group, the negative control (NC) group, GSE group, OPE group, and ROE group. During the first 7 d of trial, compared with NC and PC groups, the GSE group enhanced average daily feed intake (ADFI). From day 8–21, diquat injection resulted in reduced growth performance, increased platelet volume distribution width (PWD), malondialdehyde (MDA) concentration, and activities of alanine aminotransferase (ALT) in chick serum; it also decreased total protein (TP), albumin (ALB), globulin (GLB) concentration, activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) in chick serum; furthermore, it increased MDA concentration while decreasing GST activities in liver. The NC group exhibited lower average daily gain (ADG) than other groups. Compared with NC group, GSE group reduced ALT activities, MDA levels, and red cell distribution width (RDW), and PDW concentration; it also increased SOD, GST activities. The ROE group lowered ALT activities and MDA concentration. The OPE group decreased ALT activities, and MDA levels, RDW, and PDW concentration, and increased SOD activities of chicks. These results suggest that supplementing antioxidants in diets alleviated oxidative stress in chicks challenged by improving antioxidant capacity and liver function.

Race and sex differences in ROS production and SOD activity in HUVECs.

Black individuals and men are predisposed to an earlier onset and higher prevalence of hypertension, compared with White individuals and women, respectively. Therefore, the influence of race and sex on reactive oxygen species (ROS) production and superoxide dismutase (SOD) activity following induced inflammation was evaluated in female and male human umbilical vein endothelial cells (HUVECs) from Black and White individuals. It was hypothesized that HUVECs from Black individuals and male HUVECs would exhibit greater ROS production and impaired SOD activity. Inflammation was induced in HUVEC cell lines (n = 4/group) using tumor necrosis factor-alpha (TNF-α, 50ng/ml). There were no between group differences in ROS production or SOD activity in HUVECs from Black and White individuals, and HUVECs from Black individuals exhibited similar SOD activity at 24hr compared with 4hr of TNF-α treatment (p>0.05). However, HUVECs from White individuals exhibited significantly greater SOD Activity (p<0.05) at 24hr as compared to 4hr in the control condition but not with TNF-α treatment (p>0.05). Female HUVECs exhibited significantly lower ROS production than male HUVECs in the control condition and following TNF-α induced inflammation (p<0.05). Only female HUVECs exhibited significant increases in SOD activity with increased exposure time to TNF-α induced inflammation (p<0.05). HUVECs from White individuals alone exhibit blunted SOD activity when comparing control and TNF-α conditions. Further, compared to female HUVECs, male HUVECs exhibit a pro-inflammatory state.

Red Cabbage Anthocyanins Attenuate Cognitive Impairment By Attenuating Neuroinflammation and Regulating Gut Microbiota in Aging Mice.

Red cabbage anthocyanins may provide health benefits that may be associated with antiaging. The protection of red cabbage anthocyanin-rich extract (ARE) and cyanidin-3-diglucoside-5-glucoside-rich extract (CY3D5G) against age-related cognitive dysfunction was investigated in normal aging mice (male C57BL/6J, 12 months old) administered orally for 12 weeks. Behavioral tests showed that ARE and CY3D5G significantly decreased cognitive impairment (p < 0.05) and had no effect on motor disorder. ARE and CY3D5G increased superoxide dismutase activity by 29.18 and 23.09% and decreased malondialdehyde by 15.74 and 10.05%, respectively, compared to the control. Histological staining showed that ARE and CY3D5G treatment reduced hippocampal neuronal damage and brain-derived neurotrophic factor degeneration. ARE and CY3D5G significantly reduced IL-1β and IL-6 levels in serum and brain (p < 0.05) by promoting the MAPK signaling pathway while enriching the abundance of butyrate-producing bacteria and altering the functional profile of the microbial community. In conclusion, ARE and CY3D5G may attenuate age-related cognitive dysfunction by reducing neuroinflammation and regulating the gut-brain axis.

Chemical characterization of Callingcard Vine (Entada polystachya (L.) DC. var. polystachya) aqueous seed extract and evaluation of its cytotoxic, genotoxic and mutagenic properties.

Callingcard Vine (Entada polystachya (L.) DC. var. polystachya - Fabaceae) is a common plant in coastal thickets from western Mexico through Central America to Colombia and Brazil, especially in Amazon biome. It has been popularly used as a urinary burning reliever and diuretic. However, the plant chemical constituents are poorly understood and Entada spp. genotoxic potential have not been previously investigated. In the present study we determined the chemical composition of the aqueous E. polystachya crude seed extract (EPCSE) and evaluated the cytotoxic, genotoxic and mutagenic properties of EPCSE in Salmonella typhimurium and Chinese hamster fibroblast (V79) cells. Cytotoxic activity was also evaluated in tumor cell lines (HT29, MCF7 and U87) and non-malignant cells (MRC5). The chemical analysis by High Resolution Mass Spectrometry (HRMS) of EPCSE indicated the presence of saponin and chalcone. The results of the MTT and clonal survival assays suggest that EPCSE is cytotoxic to V79 cells. Survival analysis showed higher IC50 in non-tumor compared with tumor cell lines. EPCSE showed induction of DNA strand breaks as revealed by the alkaline comet assay and micronucleus test. Using the modified comet assay, it was possible to detect the induction of oxidative DNA base damage by EPCSE in V79 cells. Consistently, the extract induced increase lipid peroxidation (TBARS), superoxide dismutase (SOD) and catalase (CAT) activities in V79 cells. In addition, EPCSE induced mutations in S. typhimurium TA98 and TA100 strains, confirming a mutagenic potential. Taken together, our results suggest that EPCSE is cytotoxic and genotoxic to V79 cells and mutagenic to S. typhimurium. These properties can be related to the pro-oxidant ability of the extract and induction of DNA lesions. Additionally, EPCSE could inhibit the growth of tumor cells, especially human colorectal adenocarcinoma (HT29) cell line, and can constitute a possible source of antitumor natural agents.

Aerobic Exercise Ameliorates Liver Injury in Db/Db Mice by Attenuating Oxidative Stress, Apoptosis and Inflammation Through the Nrf2 and JAK2/STAT3 Signalling Pathways.

Diabetes mellitus (DM) implicates oxidative stress, apoptosis, and inflammation, all of which may contribute liver injury. Aerobic exercise is assured to positively regulate metabolism in the liver. This project was designed to investigate whether and how aerobic exercise improves DM-induced liver injury. Seven-week-old male db/db mice and age-matched m/m mice were randomly divided into a rest control group or a group that received 12 weeks of aerobic exercise by treadmill training (10 m/min). Haematoxylin and eosin (HE) staining, electron microscopy, Oil Red O staining and TUNEL assays were used to evaluate the histopathological changes in mouse liver. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TRIG), cholesterol (CHOL) were analyzed by serum biochemical analysis. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed via ELISA. Nuclear factor E2-associated factor-2 (Nrf2), nuclear factor κB (NF-κB) and JAK2/STAT3 pathway-related proteins were measured by immunofluorescence, Western blotting and q-PCR. F4/80 expression in liver tissues was assessed by immunohistochemistry. In diabetic mice, exercise training significantly decreased the levels of serum TRIG, CHOL, IL-6, TNF-α, ALT and AST; prevented weight gain, hyperglycaemia, and impaired glucose and insulin tolerance. Morphologically, exercise mitigated the diabetes-induced increase in liver tissue microvesicles, inflammatory cells, F4/80 (macrophage marker) levels, and TUNEL-positive cells. In addition, exercise reduced the apoptosis index, which is consistent with the results for caspase-3 and Bax. Additionally, exercise significantly increased SOD activity, decreased MDA levels, activated Nrf2 and decreased the expression of NF-kB, phosphorylated JAK2 and STAT3 proteins in the livers of diabetic mice. This study demonstrated that aerobic exercise reversed liver dysfunction in db/db mice with T2DM by reducing oxidative stress, apoptosis and inflammation, possibly by enhancing Nrf2 expression and inhibiting the JAK2/STAT3 cascade response.

The Effect of Silver Nanoparticles on the Digestive System, Gonad Morphology, and Physiology of Butterfly Splitfin (Ameca splendens).

The aim of this study was to determine the effects of silver nanoparticles (AgNPs) on the morphology and enzymatic activity of butterfly splitfin (Ameca splendens). Individuals of both sexes, aged about five months, were exposed to AgNPs at concentrations of 0 (control group), 0.01, 0.1, and 1.0 mg/dm3 for 42 days. On the last day of the experiment, the fish were euthanized, subjected to standard histological processing (anterior intestine, liver, and gonads), and analysed for digestive enzyme activity in the anterior intestine and oxidative stress markers in the liver. Fish in the AgNP 0.01 and 0.1 groups had the lowest anterior intestinal fold and enterocyte height. However, there were no statistically significant changes in the digestive enzyme activity in the anterior intestine. Analysis of enzymatic activity in the liver showed an increase in superoxide dismutase activity in fish in the AgNP 0.1 group. Histological analyses showed that AgNPs inhibited meiotic divisions at prophase I in a non-linear manner in ovaries and testes. In the AgNP 0.1 and 1.0 groups, the area occupied by spermatocytes was lower compared to the other groups. These results indicate that exposure to AgNPs may lead to disturbances in morphology and enzymatic activity in the liver and intestine and may lead to disruption of reproduction in populations.

CsABF3-activated CsSUT1 pathway is implicated in pre-harvest water deficit inducing sucrose accumulation in citrus fruit

Pre-harvest water deficit (PHWD) plays an important role in sugar accumulation of citrus fruit. However, the mechanism is not known well. Here, it was confirmed that PHWD promoted sucrose accumulation of citrus fruit, but had limited effect on fructose, glucose and total acid. A sucrose transporter, CsSUT1, which localizes to the plasma membrane, was demonstrated to function in sucrose transport induced by PHWD. Compared to wild-type, CsSUT1 overexpression in citrus calli stimulated sucrose, fructose and glucose accumulation, while its silencing in juice sacs reduced sucrose accumulation. Increased sugar accumulation in transgenic lines enhanced plant drought tolerance, and resulted in decreased electrolyte leakage, malondialdehyde and hydrogen peroxide contents, as well as increased superoxide dismutase activity and proline contents. An abscisic acid (ABA)-responsive transcription factor, CsABF3, was found with a same expression pattern with CsSUT1 under PHWD. Yeast one-hybrid, electrophoretic mobility shift assay and dual-luciferase assays all revealed that CsABF3 directly bound with the CsSUT1 promoter by ABA responsive elements. When CsABF3 was overexpressed in citrus calli, the sucrose, fructose and glucose concentration increased correspondingly. Further, transgenic studies demonstrated that CsABF3 could affect sucrose accumulation by regulating CsSUT1. Overall, this study revealed a regulation of CsABF3 promoting CsSUT1 expression and sucrose accumulation in response to PHWD. Our results provide a detail insight into the quality formation of citrus fruit.

The association of SOD and HsCRP with the efficacy of sulforaphane in schizophrenia patients with residual negative symptoms

ObjectivesEmerging evidence indicates a connection between oxidative stress, immune-inflammatory processes, and the negative symptoms of schizophrenia. In addition to possessing potent antioxidant and anti-inflammatory properties, sulforaphane (SFN) has shown promise in enhancing cognitive function among individuals with schizophrenia. This study aims to investigate the efficacy of combined treatment with SFN in patients with schizophrenia who experience negative symptoms and its effect on the levels of superoxide dismutase (SOD) and the inflammatory marker, high-sensitivity C-reactive protein (HsCRP).DesignForty-five patients with schizophrenia were recruited, who mainly experienced negative symptoms during a stable period. In addition to the original treatments, the patients received SFN tablets at a daily dose of 90 mg for 24 weeks. At baseline, 12 weeks, and 24 weeks, the participants were interviewed and evaluated. The reduction rate of the Positive and Negative Syndrome Scale (PANSS) was used to assess each participant. The side effects scale of Treatment Emergent Symptom Scale (TESS) was applied to assess the adverse reactions. Additionally, the levels of the SOD, HsCRP, and other indicators were examined.ResultsThe study findings revealed a significant decrease in PANSS negative subscale scores (P < 0.001). Furthermore, there was a significant increase in SOD activity and HsCRP levels (P < 0.001 and P < 0.05). Notably, the group of participants who exhibited a reduction in PANSS negative subscale scores demonstrated a significant improvement in HsCRP levels (P < 0.05).ConclusionsOur study suggests that SFN may potentially serve as a safe adjunctive intervention to improve the negative symptoms of schizophrenia. The potential mechanism by which SFN improves negative symptoms in schizophrenia patients may involve its anti-inflammatory properties, specifically its ability to reduce HsCRP levels.Trial registrationClinicalTrial.gov (ID: NCT03451734).

Flavonoid compound from Agrimonia pilosa Ledeb improves adipose insulin resistance by alleviating oxidative stress and inflammation

BackgroundResearches and practice of traditional Chinese medicine indicated that Agrimonia pilosa Ledeb could improve insulin resistance (IR) and treat type 2 diabetes (T2DM). To reveal its underling mechanisms, we isolated Flavonoid component (FC) from Agrimonia pilosa Ledeb and elucidated its effects on glucose metabolism to improve IR by suppressing oxidative stress and inflammation.MethodsAdipocytes or mice IR model was established with overdosed glucose and insulin or high-fat diet. The uptake of 2-NBDG and glucose consumption were measured to verify insulin sensitivity in vitro and vivo. Reactive oxidative species (ROS) were detected by flow cytometry, and superoxide dismutase (SOD) activity as well as the malondialdehyde (MDA) content were also measured. Meanwhile, factors associated with insulin signal pathway including PPARγ, insulin receptor substrate-1 (IRS-1), GLUT4, and oxidative stress including NF-E2-related factor 2 (Nrf2), as well as the related inflammatory cytokines such as NF-κB, IL-1β, IL-6 and TNF-α were tested. Furthermore, the JNK/PI3K/Akt signal pathway was also explored.ResultsFC extracted from Agrimonia pilosa Ledeb ameliorated the impaired glucose metabolism significantly. Further study indicated that FC could regulate the insulin signal pathway to improve insulin resistance. Moreover, it could upregulate PPARγ with the similar efficacy as pioglitazone (Piog) straightway. FC also decreased the endogenous ROS and MDA content, increased SOD activity and Nrf2 expression to facilitate oxidative homeostasis. It attenuated expression and secretion of inflammatory cytokines obviously. At last, our results indicated JNK/PI3K/Akt pathway was regulated by FC in adipocytes and adipose tissue.ConclusionFC could ameliorate glucose metabolism and improve IR. It exerted these effects by suppressing oxidative stress and inflammation. FC from Agrimonia pilosa Ledeb has a good prospect to be drugs or functional foods for IR and T2DM.

U(VI) exposure induces apoptosis and pyroptosis in RAW264.7 cells

U(VI) pollution has already led to serious harm to the environment and human health with the increase of human activities. The viability of RAW264.7 cells was assessed under various U(VI) concentration stress for 24 and 48 h. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and superoxide dismutase (SOD) activities of RAW264.7 cells under U(VI) stress were measured. The results showed that U(VI) decreased cell activity, induced intracellular ROS production, abnormal MMP, and increased SOD activity. The flow cytometry with Annexin-V/PI double labeling demonstrated that the rate of late apoptosis increased with the increase of U(VI) concentration, resulting in decreased Bcl-2 expression and increased Bax expression. The morphology of RAW264.7 cells dramatically changed after 48 h U(VI) exposure, including the evident bubble phenomenon. Besides, U(VI) also increased the proportion of LDH releases and increased GSDMD, and Ras, p38, JNK, and ERK1/2 protein expression, which indicated that the MAPK pathway was also involved. Therefore, U(VI) ultimately led to apoptosis and pyroptosis in RAW264.7 cells. This study offered convincing proof of U(VI) immunotoxicity and established the theoretical framework for further fundamental studies on U(VI) toxicity.

Qishen granule attenuates doxorubicin-induced cardiotoxicity by protecting mitochondrial function and reducing oxidative stress through regulation of Sirtuin3

Ethnopharmacological relevanceDoxorubicin (DOX) is one of the most potent chemotherapy drugs available today. However, the adverse effect of cardiotoxicity limits its clinical application. New approaches are being investigated for the treatment of doxorubicin-induced cardiotoxicity (DIC). Doxorubicin is enriched in mitochondria and it could induce imbalance of protein modification, including acetylation of mitochondria proteins, thereby inducing DIC. Restoration of mitochondria function is an effective way to attenuate DIC. The formula for traditional Chinese medicine Granules of Qishen (QSG) was derived from the classic formula “Zhen-Wu-Tang” which has been extensively used in the treatment of myocardial infarction. It consists of six traditional Chinese medicines, including Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao (Fabaceae), Salvia miltiorrhiza Bunge (Lamiaceae), Lonicera japonica Thunb. (Caprifoliaceae), Aconitum carmichaelii Debeaux (Ranunculaceae), Scrophularia ningpoensis Hemsl. (Scrophulariaceae), and Glycyrrhiza uralensis Fisch. (Fabaceae). QSG is a potential anti-DIC formula. A better understanding of the effectiveness and pharmacological mechanisms of QSG will aid in the prevention and treatment of DIC. Aim of the studyThe purpose of this research was to explore the effectiveness of QSG in the treatment of DIC and to explore whether QSG could protect mitochondrial function and reduce oxidative damage by activating Sirtuin3(SIRT3)/Acetylated-superoxide dismutase 2(Ac-SOD2) signaling pathway. Materials and methodsDOX was injected into mice through the tail vein to construct a mouse model of DOX-induced cardiotoxicity to explore the therapeutic effect of QSG in animals. Meanwhile, the H9C2 cell model was used to study the mechanism of QSG. The cardiac function was evaluated by echocardiography, hematoxylin-eosin (H&E) staining and measurement of serum levels of creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH). Oxidative damage was evaluated by 2′,7′-dichlorodihydro fluorescein diacetate (DCFH-DA) staining and Mito-SOX Red staining. Levels of total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by following the instructions of commercially available kits. In order to detect the changes in mitochondrial membrane potential, cells were stained using the mitochondrial membrane potential detection kit (JC-1). Western blot analysis was applied to detect protein expressions of SIRT3, Ac-SOD2, Acetylation Lysine (Ac-Lys), Bax and Bcl-2. H9C2 cells were treated with SIRT3 inhibitor, in order to determine if QSG had effects via the SIRT3/Ac-SOD2 pathway. ResultsIn vivo studies showed that QSG ameliorated doxorubicin-induced damage of cardiac function in DIC mice model. The ejection fraction (EF) and fractional shortening (FS) were all up-regulated by QSG treatment. QSG decreased MDA levels and increased SOD activity. Meanwhile, doxorubicin induced high level of protein acetylation and QSG restored the acetylated protein back to normal levels. In particular, QSG upregulated expression of SIRT3 and downregulated Ac-SOD level. In vitro study demonstrated that QSG restored mitochondrial membrane potential, increased ATP level and reduced mitochondrial ROS production. When H9C2 cells were co-incubated with SIRT3 inhibitor, the efficacies of QSG on mitochondrial function were abrogated. Meanwhile, the regulative effects of QSG on SIRT3/Ac-SOD2 pathway were also abolished. ConclusionThis study demonstrates that QSG is effective in treating DIC. QSG ameliorates oxidative damage and protects mitochondrial function partly by restoring protein acetylation level and by activating the SIRT3/Ac-SOD2 pathway.

Exposure to metam sodium-based pesticide impaired cognitive performances in adult mice: Involvement of oxidative damage and glial activation

Cognitive integrity is a critical aspect of neurological function, and a decline in cognitive function is a hallmark of neurotoxicity. Oxidative stress is a significant pathological feature contributing to cognitive deficits that can arise from exposure to environmental pollutants such as pesticides. Among these, Metam sodium-based pesticides (MS-BP) are an emergent type of pesticide widely used in the agriculture and public health sectors for controlling pests and diseases. Our prior research has shown that animals exposed to MS-BP during the early stages of brain development caused cognitive impairments. In the present study, we tested whether exposure to this compound in a fully matured brain would affect cognitive performance and induce oxidative damage to the central nervous system. In this context, adult mice received chronic treatment with increasing doses of MS-BP and subjected to a set of behavioral paradigms. Following behavioral assessment, oxidative stress and glial activation were evaluated. Our main findings showed that MS-BP chronic exposure impaired recognition and short- and long-term memory. These alterations were accompanied by increased superoxide dismutase activity and malondialdehyde level and a marked decrease in catalase activity in specific brain areas. Moreover, exposure to MS-BP is associated with a significant rise in the density of astrocytic and microglial markers, indicating a possible glial cell response within the prefrontal cortex and hippocampus. The present work demonstrated that MS-BP altered cognitive performance likely through oxidative damage to the brain.

Screening of tolerance of Atriplex vulgatissima under zinc or lead experimental conditions. An integrative perspective by using the integrated biological response index (IBRv2).

The search for plants with a high capacity to tolerate and accumulate metals is an important issue in phytoremediation. In this sense, this study was conducted in the halophyte Atriplex vulgatissima to evaluate the effects of different concentrations of lead (Pb, 50 and 100 μM) or zinc (Zn, 100 and 200 μM) on morphological, physiological, and biochemical parameters as well as the accumulation patterns of this species. The results indicated that while essential metal Zn showed high translocation from roots to shoots (TF > 1), non-essential Pb was mainly accumulated in the roots (BCF>1). Regarding shape, both metals induced slenderness of the blade, but only Zn treatment reduced leaf size. No difference in biomass production and photosynthetic parameters was found between Pb and Zn treatments. Pb treatments did not show significant differences between treatments regarding water content (WC), pigment concentration, and the activity of superoxide dismutase (SOD) and guaiacol peroxidase (GPx), but did result in a decrease in catalase activity at 100 μM Pb. On the other hand, 200 μM Zn leads to a clear reduction in WC and pigment concentrations, along with an increase in SOD and GPx activities. In addition, ascorbate peroxidase (APx) activity showed a hormesis effect at 50 μM Pb and 100 μM Zn. Malondialdehyde increased with both Pb and Zn treatments. The integrated biological index (IBRv2) indicated that 200 μM Zn was the most affected treatment (IBRv2 = 19.02) and that under the same concentrations of metals (100 μM Pb or Zn), Pb treatments presented major stress (IBRv2 = 11.55). A. vulgatissima is a metallophyte with the potential for Pb phytostabilization and Zn phytoextraction, as well as a bioindicator of these metals. Its high biomass and deep roots, combined with its halophytic traits, make it suitable for bioremediation and monitoring programs.

Features of reproductive capacity and state of prooxidant-antioxidant homeo-stasis in breeding boars of different breeds

Temperature stress is caused by the long-term effect of high or low average daily temperature, which leads to a decrease in the quality of sperm in fetuses and processes from the formation of the leading herd of pigs, which causes a reduction in the production of livestock products. Changes in lipid peroxidation accompany the inhibition of reproductive function in breeding boars of various breeds. The research method was to determine the features of pro-oxidant-antioxidant homeostasis in breeding boars of different species depending on the keeping conditions. For the experiment, six breeding boars of other breeds, similar in age, live weight, and quality of sperm production, were selected, and 2 study groups of 3 heads in the skin were formed. The first group consisted of animals of the large white breed, and the second group – was from Myrhorod. Animals were fed following feed regulations. The influence of heat stress on the quality of sperm production of breeding boars of the large white breed is manifested in a decrease in the following indicators: ejaculate volume – by 20.3 %, sperm motility – by 20.6 %, sperm concentration – by 28.3 %, the number of live sperm – by 54.6 %, heat resistance by 26.4 %. As the temperature rises, peroxidation processes accelerate – the content of TBC-active compounds in sperm increases by 1.3 times. Catalase activity in seminal plasma and sperm increases by 16.0 % and 21.0 %, respectively. An increase in indoor temperature harms the indicators of sperm production of breeding boars of the Myrhorod breed: ejaculate volume – by 18.6 %, sperm motility – by 10.5%, sperm concentration – by 30.3 %, number of live sperm – by 34.7 %, thermal resistance – by 23.5 %. The changes occur against the background of an increase in superoxide dismutase activity – 21.0 % (sperm) and 5.0 % (sperm plasma), a decrease in ascorbic acid saturation by 10.0 % and 52.2 %, respectively. The establishment of an interbreed difference in the quality of ejaculates in the direction of the superiority of indicators in animals of the large white breed compared to the Myrhorod breed on the 60th day of the primary period in the summer in terms of ejaculate volume (p = 0.001) and sperm concentration was established. However, according to the level of heat resistance of sperm, animals of the second breed were characterized by higher values. At the end of the 45th day of temperature stress, a probable predominance of ascorbic acid (p = 0.001) and dehydroascorbic acid (p = 0.01) content was observed in the semen of animals of the Myrhorod breed compared to large white.

Neurodegenrative changes in retina of rats with streptozotocin-induced diabetes under conditions of treatment with niacin-oxy-ethylidene-diphosphonate germanate (MIGU-4)

Background: Diabetes is accompanied by neurodegenerative changes in the retina. The determination of retinal function parameters under conditions of experimental diabetes may allow for the development of new approaches to pharmacological vision correction. Purpose: To assess changes in the metabolic (lipid peroxidation and antioxidant defence) and functional characteristics (electroretinography (ERG)) of the retina in the rat with streptozotocin (STZ)-induced diabetes, treated with niacin-oxy-ethylidene-diphosphonate germanate (MIGU-4) and a reference drug, diazepam. Material and Methods: Diabetes was induced intraperitoneally (i.p.) in Wistar male rats by streptozotocin (STZ 65 mg/kg). Four weeks thereafter, the rats received a two-week course of a daily dose of MIGU-4 (5.0 mg/kg or 25.0 mg/kg) or diazepam (0.5 mg/kg or 1.5 mg/kg). The electroretinogram (ERG) was obtained, the animals were euthanized and retinal malondialdehyde (MDA) levels and superoxide dismutase (SOD) and catalase (CAT) activity were determined. Results: In rats with untreated STZ-induced diabetes, the retinal MDA level was 3.71 times increased and CAT activity was 35% lower, compared to controls, whereas the SOD activity was half of the activity found in controls (р less 0.05). In diabetic animals treated with MIGU-4 i.p. at a 25.0-mg/kg daily dose, the retinal MDA level was 63.2% lower, whereas the CAT activity and SOD activity were 41.9% and 27.6%, respectively, higher, than in untreated diabetic rats (р less 0.05). In diabetic animals treated with diazepam i.p. at a 1.5-mg/kg daily dose, the retinal MDA level was 59.2% lower, whereas the CAT activity and SOD activity were 44.4% and 32.1%, respectively, higher, than in untreated diabetic rats (р less 0.05). In untreated diabetic rats, the ERG b-wave amplitude was 39.2% lower, ERG a-wave and b-wave latencies, 23.4% and 14.0%, respectively, higher, and the a-wave amplitude recovery rate, 38.8% lower than in controls (р less 0.05). The use of a 25.0-mg/kg daily dose of MIGU-4 resulted in a 29.7% and 33.9%, respectively, increase in the ERG b-wave amplitude and the a-wave amplitude recovery rate compared to untreated diabetic rats (р less 0.05). The use of a 1.5-mg/kg daily dose of diazepam resulted in a 25.0% and 30.0%, respectively, increase in the above ERG parameters compared to untreated diabetic rats (р less 0.05). In untreated diabetic rats, the number of squares crossed (SK) was 29.4% lower (р less 0.05); the number of central squares crossed (CSC), 52.1% lower (р less 0.05); the number of upright postures (UP), 34.2% lower; and the defecation bolus number, 32.4% higher than in controls (р less 0.05). After MIGU-4 (25-mg/kg) withdrawal, there were no more differences in SK, CSC, UP and defecation bolus numbers between treated diabetic rats and controls. In addition, the number of CSC was 4.27 times lower than in controls, and half of that in untreated diabetic animals (р less 0.05). In diabetic rats treated with diazepam, the number of UP was 2.56 times lower than in controls (р less 0.05), and 40.7% lower than in untreated diabetic rats (р less 0.05), whereas the defecation bolus number was 40.5% higher than in controls (р less 0.05). Conclusion: STZ-induced diabetes is accompanied by an impairment of the oxidant/ antioxidant balance in the retina with an increase in retinal MDA, decrease in retinal SOD and CAT activity, and ERG abnormalities such as reduced ERG amplitude and increased ERG latency. A course treatment with niacin-oxy-ethylidene-diphosphonate germanate (MIGU-4) i.p. at a daily dose of 25.0 mg/kg provides for a decrease in retinal MDA and an increase in retinal SOD and CAT activity and ERG wave amplitude The withdrawal of a two-week treatment with MIGU-4 i.p. at a daily dose of 25.0 mg/kg decreased open-field anxiety-like behaviors, whereas the withdrawal of a two-week treatment with diazepam i.p. at a daily dose of 1.5 mg/kg increased open-field anxiety-like behaviors. The corrective effect of treatment with MIGU-4 corresponds to the corrective effect of treatment with diazepam.

Glycyrrhizic acid enhances the anticancer activity of cisplatin in the human ovarian cancer cell line

This study aimed to investigate the effects of glycyrrhizic acid (GL) on the anticancer activity of cisplatin in A2780 ovarian cancer cells. Cultured A2780 cells were treated with different concentrations of GL and cisplatin individually and in combination. The MTT assay, flow cytometry, wound-healing, and clonogenic assay, were used to determine cell viability, apoptosis, migration, and colony formation, respectively. The effects on superoxide dismutase (SOD) activity were also evaluated. QPCR was used to study the effects of individual and combined treatments with GL and cisplatin on the expression levels of migration genes (MMP2 and MMP9), and some apoptosis pathway genes (caspase-3, −8, −9, and BCL2). A synergistic effect was observed between GL and cisplatin (CI < 1). Combination therapy was significantly more effective in reducing cell viability, suppressing migration and colony formation, inducing apoptosis, and altering gene expression compared to single therapies. GL significantly increased SOD activity. The relative expression of caspase −3, −8, and − 9 increased significantly, and the expression levels of MMP2 and MMP9 decreased significantly in the treated cells. Our results indicate that GL enhances the anticancer activity of cisplatin in the A2780 cell line. Therefore, the combination of GL and cisplatin can be proposed as a promising therapeutic strategy for ovarian cancer.

Hub Gene Identification and Heat-Stress-Related Transcriptional Regulation Mechanism in Cabbage (Brassica oleracea L.)

Cabbage is a heat-stress-sensitive cool-season crop. When exposed to high temperatures, cabbage plants can experience reduced growth, wilting, leaf yellowing, and premature bolting (the formation of a flowering stem). The regulatory mechanism controlling heat stress is poorly understood in cabbage. To investigate this mechanism, physiological changes and transcriptional profiling for different heat treatment times were analyzed in this study. The results showed that superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities were enhanced under heat stress. In particular, the increase in SOD and POD activities after 12 h of heat treatment was greater than that after 4 h of heat treatment. With increasing heat treatment duration, the leaf CAT activity and H2O2 content decreased after the initial increase. The electrolyte leakage and malondialdehyde (MDA) content dropped significantly, while the proline content increased. Alongside that, 7007 and 5537 upregulated genes were identified in the experimental group treated with heat stress for the 4 h and 12 h treatments, respectively. We found that 10,479 DEGs were shared in the heat stress treatment, of which 1241 were associated with the heat treatment time. By integrating the expression patterns and functional annotations of genes related to heat stress, we identified 15 hub genes that respond to heat stress in cabbage. Meanwhile, we had constructed a physiological to molecular model of cabbage response to long-term heat stress. These findings provide new insights for the comprehensive analysis of cabbage response to heat stress and genetic resources for breeding new varieties of cabbage with heat tolerance via genetic engineering.

Individual and binary exposure of embryonic zebrafish (Danio rerio) to single-walled and multi-walled carbon nanotubes in the absence and presence of dissolved organic matter

The available toxicological information was inadequate to assess the potential ecological risk of a mixture of different nanostructured carbon nanotubes (CNTs) to aquatic organisms, especially for the co-existence of mixed CNTs with dissolved organic matter (DOM). Herein, we investigated individual and binary exposure of zebrafish (Danio rerio) embryos to single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) in the absence and presence of DOM. Results indicated that embryonic chorions were more resistant to mixed-type CNTs than to single-type CNTs, yet the addition of DOM decreased this resistance. The mixed-type CNTs increased the antioxidant capacity of zebrafish embryos by increasing superoxide dismutase activity in comparison to the single-type CNTs. Furthermore, the mixed-type CNTs caused oxidative damage to the zebrafish embryos, characterized by an increase in malondialdehyde level. Nevertheless, the activation of the antioxidant defense system was modulated by the presence of DOM. Transcriptome sequencing analysis showed that the number of unique genes (UGs) and differentially expressed genes (DEGs) between the mixed-type CNTs and control groups was significantly enhanced compared to the single-type CNTs. DOM increased the number of UGs and up-regulated DEGs, but decreased the number of down-regulated DEGs. GO classification analysis revealed that the mixed-type CNTs mainly altered the cellular component process of single-type CNTs to induce joint effects. DOM generally enhanced the GO enrichment of DEGs in D. rerio embryos exposed to the mixed-type CNTs during the biological process. KEGG pathway enrichment analysis for the mixed-type CNTs showed enrichment of DEGs encoding ether lipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, citrate cycle, and biosynthesis of nucleotide sugars. However, DOM allowed more specific KEGG pathways towards the mixed-type CNTs to be identified. Despite the mixed-type CNTs exhibiting differential expression of functional genes compared to the control and single-type CNTs, DOM could regulate the expression of these functional genes associated with oxidative stress response, carbohydrate metabolism, endoplasmic reticulum stress, neuroendocrine, osmotic stress, and DNA damage and repair. Our study thus paves a solid way for exploring the molecular mechanism of aquatic toxicity of multiple nanomaterials under field-relevant conditions.

Penfluroidol Attenuates the Imbalance of the Inflammatory Response by Repressing the Activation of the NLRP3 Inflammasome and Reduces Oxidative Stress via the Nrf2/HO-1 Signaling Pathway in LPS-Induced Macrophages.

Excessive inflammatory responses and reactive oxygen species (ROS) formation play pivotal roles in the pathogenesis of sepsis. Penfluroidol (PF), an oral long-acting antipsychotic drug, has been suggested to possess diverse biological properties, including antischizophrenia, antitumour effect, and anti-inflammatory activity. The purpose of this research was to explore the anti-inflammatory and antioxidative effects of penfluroidol on lipopolysaccharide (LPS)-related macrophages. The viability of RAW264.7 and THP-1 cells was measured by Enhanced Cell Counting Kit-8 (CCK-8). The production of nitric oxide was evaluated by the Nitric Oxide Assay Kit. The generation of pro-inflammatory monocytes was detected by qRT-PCR (quantitative real-time PCR) and ELISA (enzyme-linked immunosorbent assay). Oxidative stress was assessed by measuring ROS, malondialdehyde (MDA), and superoxide dismutase (SOD) activity. The protein expression of the Nrf2/HO-1/NLRP3 inflammasome was detected by western blotting. Our results indicated that no cytotoxic effect was observed when RAW264.7 and THP-1 cells were exposed to PF (0-1 μm) and/or LPS (1 μg/ml) for 24 hr. The data showed that LPS, which was repressed by PF, facilitated the generation of the pro-inflammatory molecules TNF-α and IL-6. In addition, LPS contributed to increased production of intracellular ROS compared with the control group, whereas the administration of PF effectively reduced LPS-related levels of ROS. Moreover, LPS induced the generation of MDA and suppressed the activities of SOD. However, PF treatment strongly decreased LPS-induced MDA levels and increased SOD activities in the RAW264.7 and THP-1 cells. Furthermore, our research confirmed that penfluroidol repressed the secretion of pro-inflammatory molecules by limiting the activation of the NLRP3 inflammasome and reducing oxidative effects via the Nrf2/HO-1 signaling pathway. Penfluroidol attenuated the imbalance of the inflammatory response by suppressing the activation of the NLRP3 inflammasome and reduced oxidative stress via the Nrf2/HO-1 signaling pathway in LPS-induced macrophages.