Superoxide Dismutase mRNA Expression Research Articles

Effect of Secretome-Hypoxia Mesenchymal Stem Cells on Regulating SOD and MMP-1 mRNA Expressions in Skin Hyperpigmentation Rats

BACKGROUND: Ultraviolet B (UVB) radiation is the main factor causing hyperpigmentation. MSC secretome contains bioactive soluble molecules such as cytokines and growth factors that can accelerate skin regeneration. However, the molecular role of the secretome in hyperpigmentation is still unclear. AIM: This study aimed to determine the effect of secretome hypoxia mesenchymal stem cells (S-HMSC) gel on the expression of superoxide dismutase (SOD) and matrix metalloproteinases (MMP-1) genes in skin tissue of hyperpigmented rats induced by UVB light exposure. MATERIALS AND METHODS: Experimental research with post-test only control group. The control, base gel, T1 and T2 groups were UVB irradiated 6 times in 14 days at 302 nm with an minimal erythema dose of 390 mJ/cm2, respectively, while sham group did not receive UVB exposure. T1 was given 100 uL of S-HMSC gel and T2 was given 200 uL of S-HMSC gel every day for 14 days, while base gel received base gel. On day 15, skin tissue was isolated and analyzed for SOD and MMP-1 expression using qRT-PCR. RESULTS: The relative expression of the SOD gene in the treatment group (P1 = 0.47 ± 0.20, P2 = 1.22 ± 0.47) increased with increasing dose compared to the control group (UVB = 0.05 ± 0.01, Base gel = 0.05 ± 0.02). The relative expression of the MMP-1 gene in the treatment group (T1 = 5.82 ± 1.16, T2 = 2.86 ± 1.57) decreased with increasing dose compared to the control group (Control = 10.10 ± 2.31, and Base gel = 9.55 ± 1.29). CONCLUSION: Administration of S-HMSC gel can increase SOD gene expression and decrease MMP-1 gene expression in skin tissue of hyperpigmented rats model induced by UVB light.

Effects of bamboo leaf extract on energy metabolism, antioxidant capacity, and biogenesis of small intestine mitochondria in broilers.

The present study was carried out to investigate the effects of bamboo leaf extract (BLE) on energy metabolism, antioxidant capacity, and biogenesis of broilers' small intestine mitochondria. A total of 384 one-day-old male Arbor Acres broiler chicks were randomly divided into four groups with six replicates each for 42 d. The control group was fed a basal diet, whereas the BLE1, BLE2, and BLE3 groups consumed basal diets with 1.0, 2.0, and 4.0 g/kg of BLE, respectively. Some markers of mitochondrial energy metabolism including isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase and some markers of redox system including total superoxide dismutase, malondialdehyde, and glutathione were measured by commercial colorimetric kits. Mitochondrial and cellular antioxidant genes, mitochondrial biogenesis-related genes, and mitochondrial DNA copy number were measured by quantitative real-time-polymerase chain reaction (qRT-PCR). Data were analyzed using the SPSS 19.0, and differences were considered as significant at P < 0.05. BLE supplementation linearly increased jejunal mitochondrial isocitrate dehydrogenase (P < 0.05) and total superoxide dismutase (P < 0.05) activity. The ileal manganese superoxide dismutase mRNA expression was linearly affected by increased dietary BLE supplementation (P < 0.05). Increasing BLE supplementation linearly increased jejunal sirtuin 1 (P < 0.05) and nuclear respiratory factor 1 (P < 0.05) mRNA expression. Linear (P < 0.05) and quadratic (P < 0.05) responses of the ileal nuclear respiratory factor 2 mRNA expression occurred with increased dietary BLE levels. In conclusion, BLE supplementation was beneficial to the energy metabolism, antioxidant capacity, and biogenesis of small intestine mitochondria in broilers. The dose of 4.0 g/kg BLE demonstrated the best effects.

Modulation of Virulence-Associated Traits in Aspergillus fumigatus by BET Inhibitor JQ1.

Aspergillus fumigatus is a disease-causing, opportunistic fungus that can establish infection due to its capacity to respond to a wide range of environmental conditions. Secreted proteins and metabolites, which play a critical role in fungal-host interactions and pathogenesis, are modulated by epigenetic players, such as bromodomain and extraterminal domain (BET) proteins. In this study, we evaluated the in vitro and in vivo capability of the BET inhibitor JQ1 to modulate the extracellular proteins and virulence of A. fumigatus. The abundance of 25 of the 76 extracellular proteins identified through LC-MS/MS proteomic analysis changed following JQ1 treatment. Among them, a ribonuclease, a chitinase, and a superoxide dismutase were dramatically downregulated. Moreover, the proteomic analysis of A. fumigatus intracellular proteins indicated that Abr2, an intracellular laccase involved in the last step of melanin synthesis, was absent in the JQ1-treated group. To investigate at which level this downregulation occurred and considering the ability of JQ1 to modulate gene expression we checked the level of ABR2, Chitinase, and Superoxide dismutase mRNA expression by qRT-PCR. Finally, the capacity of JQ1 to reduce the virulence of A. fumigatus has been proved using Galleria mellonella larvae, which are an in vivo model to evaluate fungal virulence. Overall, the promising activity exhibited by JQ1 suggests that A. fumigatus is sensitive to BET inhibition and BET proteins may be a viable target for developing antifungal agents.

Honokiol Microemulsion Causes Stage-Dependent Toxicity Via Dual Roles in Oxidation-Reduction and Apoptosis through FoxO Signaling Pathway.

Honokiol, the main bioactive extract of Magnolia officinalis, exhibits extensive therapeutic actions. Its treatment for advanced non-small cell lung cancer is undergoing clinical trials in China. However, the published safety evaluation studies have focused on extract mixtures of Magnolia officinalis in which the honokiol content was well below the reported clinical dose of the honokiol monomer. Therefore, safety assessment of the honokiol monomer is urgently needed. Our previous studies have already demonstrated that a high dose of the honokiol microemulsion (0.6 μg/mL) induces developmental toxicity in rats and zebrafish by inducing oxidative stress. By exploring the relationship between time and toxicity, we found that developmental toxic responses were stage-dependent. They mainly occurred within the first 24 h post fertilization (hpf) especially the first 12 hpf. In zebrafish, low doses of honokiol microemulsion (0.15, 0.21 μg/mL) significantly decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the mRNA expression of bcl-2. In contrast, high dose (0.6 μg/mL) increased the levels of ROS and MDA, decreased activities and mRNA expression of superoxide dismutase (SOD) and catalase (CAT), and increased mRNA expression of bax, c-jnk, p53 and bim. By acridine orange staining, we found that a high dose of honokiol microemulsion induced apoptosis mainly in zebrafish brain. In rat pheochromocytoma cells (PC12 cells), low doses of the honokiol microemulsion (1, 5, 10 µM) exerted a protective effect against H2O2-induced oxidative damage while high doses (≥20 µM) induced oxidative stress, which further confirms the dual effects of honokiol microemulsion on nerve cells. These dual roles of the honokiol microemulsion in oxidation-reduction reactions and apoptosis may be regulated by the forkhead box class O (FoxO) signaling pathway. Due to the potential of developmental toxicity, we recommend that the administration of high dose honokiol microemulsion in pregnant women should be considered with caution.

Hydrogen sulfide treatment improves quality attributes via regulating the antioxidant system in goji berry (Lycium barbarum L.)

Hydrogen sulfide (H2S) has been identified as a critical gaseous signaling chemical. Herein, the effects of H2S treatment on the postharvest goji berries and antioxidant enzyme activities were determined. H2S application delayed the decay index, loss of firmness, color, flavor, and total sugars and loss of total protein, betaine and ascorbic acid in goji berries during postharvest storage. Meanwhile, H2S noticeably reduced the MDA, H2O2, and O2− accumulation. Additionally, it was shown that H2S increased the activity of catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), glutathione reductase (GR) and superoxide dismutase (SOD) while decreased the quantity of lipoxygenase (LOX). The mRNA expression of LDC, DCD, CAT, APX, POD, GR and SOD was up-regulated but LOX, RBOH-b and RBOH-e was down-regulated in goji berries after H2S treatment. Altogether, H2S could efficiently delay the senescence, improves postharvest quality, increase the bioactive compounds accumulation, and boost the antioxidant capacity of goji berries through modulating antioxidant enzyme system.

Redox stress and metal dys-homeostasis appear as hallmarks of early prion disease pathogenesis in mice

Neurodegenerative diseases are associated with a multitude of dysfunctional cellular pathways. One major contributory factor is a redox stress challenge during the development of several protein misfolding conditions including Alzheimer's (AD), Parkinson's disease (PD), and less common conditions such as Creutzfeldt Jakob disease (CJD). CJD is caused by misfolding of the neuronal prion protein and is characterised by a neurotoxic unfolded protein response involving chronic endoplasmic reticulum stress, reduced protein translation and spongiosis leading subsequently to synaptic and neuronal loss. Here we have characterised prion disease in mice to assess redox stress components including nitrergic and oxidative markers associated with neuroinflammatory activation. Aberrant regulation of the homeostasis of several redox metals contributes to the overall cellular redox stress and we have identified altered levels of iron, copper, zinc, and manganese in the hippocampus of prion diseased mice. Our data show that early in disease, there is evidence for oxidative stress in conjunction with reduced antioxidant superoxide dismutase mRNA and protein expression. Moreover, expression of divalent metal transporter proteins was reduced for Atp7b, Atox1, Slc11a2, Slc39a14 at 6–7 weeks but increased for Slc39a14 and Mt1 at 10 weeks of disease. Our data present evidence for a strong pro-oxidant environment and altered redox metal homeostasis in early disease pathology which both may be contributory factors to aggravating this protein misfolding disease.

Distinct vulnerability to oxidative stress determines the ammonia sensitivity of crayfish (Procambarus clarkii) at different developmental stages

Red swamp crayfish (Procambarus clarkii) has increasingly become a high-value freshwater product in China. During the intensive cultivation, excessive ammonia exposure is an important lethal factor of crayfish. We investigated the toxic effects and mechanisms of ammonia on crayfish at two different developmental stages. A preliminary ammonia stress test showed a 96-h LC50 of 135.10 mg/L and 299.61 mg/L for Stage_1 crayfish (8.47 ± 1.68 g) and Stage_2 crayfish (18.33 ± 2.41 g), respectively. During a prolonged ammonia exposure (up to 96 h), serum acid phosphatase and alkaline phosphatase showed a time-dependent decrease. Histological assessment indicated the degree of hepatopancreatic injury, which was mainly characterized as tubule lumen dilatation, degenerated tubule, vacuolization and dissolved hepatic epithelial cell, increased with exposure time. Enhanced malondialdehyde level and reduced antioxidant capacity of hepatopancreas were also observed. The mRNA expression and activity of catalase and superoxide dismutase showed an initial up-regulation within 24 h, and then gradually down-regulated with the exposure time. In the post-treatment recovery period, the Stage_2 crayfish exerted a stronger antioxidant and detoxification capacity than that of the Stage_1 crayfish, and thus quickly recovered from the ammonia exposure. Our findings provide a further understanding of the adverse effects of ammonia stress and suggest guidelines for water quality management during crayfish farming.

Vitamin E and selenium partially prevent cytotoxicity, oxidative stress and DNA damage induced by T-2 toxin in bovine Leydig cells

The objective of this study was to explore the protective mechanism of Vitamin E (VE) and selenium (Se) against T-2 toxin-induced oxidative damage of bovine Leydig cells. Leydig cells were isolated, cultured and divided into five treatment groups such as: control, T-2, Se + T-2, VE + T-2 and VE + Se + T-2. After treatment for 24 h, the cells and supernatants were harvested to examine the cell viability, the activities and mRNA expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), the content of malondialdehyde (MDA) and DNA damage. Results showed that T-2 toxin exposure significantly reduced the cell viability, increased the MDA level, reduced GSH-Px, SOD and CAT activities and increased DNA damage (P < 0.05). Meanwhile, T-2 toxin was attributed to the down-regulation of the mRNA expression of GSH-Px, SOD and CAT (P < 0.05). However, VE and Se reduced T-2 toxin-induced oxidative damage and tended to maintain normal levels (P < 0.05). Furthermore, VE and Se substantially up-regulated the activities and mRNA expressions of the GSH-Px, SOD and CAT. In conclusion, VE and Se, due to its anti-oxidative ability, could ameliorate T-2 toxin-induced cytotoxicities by regulating oxidative stress in bovine Leydig cells.

Licorice Extract Supplementation Affects Antioxidant Activity, Growth-Related Genes, Lipid Metabolism, and Immune Markers in Broiler Chickens.

The objective of this study was to evaluate the Glycyrrhiza glabra effect on growth performance, blood parameters, antioxidant and lysosomal activity, histology and immunohistochemistry of liver and intestine, and the gene expression profile of broiler chickens. A total of 180 Cobb500 broiler chicks (one-week-old) were used in this study. Chicks were distributed randomly into three treatment groups; the first group received drinking water without any supplementation (control group). In contrast, birds in groups 2 and 3 received licorice supplementation in drinking water with 0.4 and 0.8 g licorice/liter, respectively. Results revealed that licorice at a 0.4 g/L of water level improved body weight, weight gain, feed intake, and FCR. Licorice also exhibits a broad range of biological activities such as hypolipidemic, hypoglycemic, hepatoprotective, immunostimulant, and antioxidant effects. The morphometric analysis of different parameters of the intestine revealed a significant increase in the intestinal villi length, width, and villi length/crypt depth in the group supplemented with licorice 0.4 gm/L compared to other groups. The number of CD3 positive in both duodenum and ileum was increased in the licorice 0.4 gm/L group compared to other groups. The expression of growth-related genes was significantly increased with licorice supplementation and modulation of the lipid metabolism genes in the liver and upregulated to the mRNA expression of both superoxide dismutase (SOD1) and Catalase (CAT). Our results revealed that licorice supplementation increased the growth performance of broiler chickens and impacted the birds’ antioxidant activity through modulation of the growth-related genes, lipid metabolic markers, and antioxidant-related pathways.

Environmentally relevant dose of the endocrine disruptor tributyltin disturbs redox balance in female thyroid gland

Tributyltin (TBT) is an endocrine disruptor used as a biocide in nautical paints. Even though many TBT effects in marine species are known, data in mammals are scarce, especially regarding the thyroid gland. The present study aimed to evaluate the effect of a subchronic exposure to TBT on thyroid oxidative stress of female Wistar rats. Rats received vehicle (control group), 200 or 1000 ng TBT/kg body weight/day for 40 days. After euthanasia, one part of the thyroids were collected in order to assess iodide uptake; activity and/or mRNA expression of thyroperoxidase (TPO) and dual oxidases (DUOXs); activity and/or mRNA expression of catalase, glutathione peroxidase, superoxide dismutase and NADPH oxidase 4 (CAT, GPx, SOD and NOX4); 4-hydroxynonenal (4-HNE) expression and total thiol groups levels; and mRNA expression of estrogen receptors alpha and beta (ERα and ERβ). The remaining part of the thyroid was processed for morphological analysis of estrogen receptor alpha (ERα) and for collagen deposition. Iodide uptake was not changed with treatments. TPO activity and expression were increased in the TBT1000 group (259.81% and 95.17%). The activity, but not mRNA, of CAT (17.36% TBT200; 27.10% TBT1000) and GPx (29.24% TBT200; 28.97% TBT1000) were decreased by TBT. SOD and NADPH oxidase activity, as well as thiol group and 4-HNE levels remained unchanged. Interstitial collagen deposition increased in the TBT200 group (39.54%). The mRNA expression of ERα increased in TBT-treated rats (44.87% TBT200; 36.43% TBT1000), while protein expression was increased but not reaching significance (TBT1000, p = 0.056) by TBT. Therefore, our results show that TBT increases TPO expression and reduces antioxidant enzyme activities in the thyroid gland leading to oxidative stress. Some of these effects could be mediated by the ERα pathway.

산란계에서 Coenzyme Q10 급여가 혈액 및 간 조직의 항산화 작용에 미치는 영향

The objective of this study was to investigate the effects of dietary coenzyme Q10 (CoQ10) sources on the antioxidant defense system in the blood and liver of laying hens. Thirty-six 40-wk old Lohmann Brown hens were randomly assigned to three groups based on body weight, with four cages with three layers each. Laying hens were divided into one of the following groups: control (CON), powdered CoQ10 (PCoQ, 100 mg/kg diet), and emulsified CoQ10 (ECoQ, 100 mg/kg diet). All hens were fed a control diet or a control diet supplemented with powdered or emulsified CoQ10 ad libitum for five weeks. There were no differences in body weight, weight gain, and organ weights among the treatment groups, including the liver and spleen. The blood total antioxidant power (TAP) in the ECoQ group increased (<i>P&lt;0.05</i>) by approximately 2-fold compared to that in the CON group. However, there was no significant difference in blood TAP levels between the PCoQ and ECoQ groups, although a decreasing trend <i>(P&lt;0.13)</i> was observed for levels of TAP in the ECoQ group. The mRNA expression and specific activities of superoxide dismutase, glutathione peroxidase, and catalase in the liver were not affected by dietary CoQ10 or type of CoQ10. However, hepatic lipid peroxidation in the ECoQ group was lower (<i>P&lt;0.05</i>) than in the CON group. In conclusion, emulsified CoQ10 increased blood TAP and decreased hepatic lipid peroxidation without affecting antioxidant enzymes, suggesting that emulsified CoQ10 might be more applicable as an active antioxidant supplement than powdered type in laying hens.

Leucine protects bovine intestinal epithelial cells from hydrogen peroxide-induced apoptosis by alleviating oxidative damage.

The present study aimed to investigate whether leucine (Leu) alleviates oxidative injury in bovine intestinal epithelial cells (BIECs) induced by hydrogen peroxide (H2 O2 ), as well as the underlying molecular mechanisms. BIECs were treated with H2 O2 (1 mmol L-1 ) and/or Leu (0, 0.9, 1.8 or 3.6 mmol L-1 ) for 2h. Leu increased cell viability (P < 0.05) and decreased the release of lactate dehydrogenase (P < 0.05) in BIECs challenged by H2 O2 . Then, the cells were treated with H2 O2 (1 mmol L-1 ) and/or Leu (1.8 mmol L-1 ) for 2h. Compared with the H2 O2 group, cells treated with Leu and Leu + H2 O2 exhibited increased (P < 0.05) mRNA and protein expression of superoxide dismutase 2 (SOD2), catalase (CAT), glutathione peroxidase 1 (GPx1), heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2). BIECs treatment with Leu significantly reduced (P < 0.05) apoptosis induced by H2 O2 . BIECs were transfected with Nrf2 small interfering RNA (siRNA) for 48 h and/or treated with H2 O2 (1 mmol L-1 ) and/or Leu (1.8 mmol L-1 ) for another 2h. Transfection with Nrf2 siRNA abrogated the protective effect of Leu against H2 O2 -induced apoptosis and the mRNA and protein expression of SOD2 (P < 0.05). These results indicate that Leu promotes the relative expression of antioxidant enzymes (SOD2, CAT and GPx1) and phase II detoxification enzymes (HO-1) by upregulating nuclear Nrf2 and activating the Nrf2 signaling pathway, thus enhancing the antioxidant capacity of cells. © 2022 Society of Chemical Industry.

Effect of in ovo manganese injection on the embryonic development, antioxidation, hatchability, and performances of offspring broilers under normal and high temperatures

Two experiments were carried out to study the effect of in ovo manganese (Mn) injection on the embryonic development, antioxidation, hatchability, and performances of offspring broilers under normal temperature (NT) and high temperature (HT). Experiment 1 was conducted to investigate the effect of in ovo Mn injection on the embryonic hatchability of Arbor Acres broiler breeders. On D 9 of incubation, a total of 684 fertilized eggs were randomly allocated to 6 treatments: the non-injected positive control (niPC) and treatments injected with 0 (the negative control, iNC), 6.25, 12.5, 25.0, or 50.0 μg Mn/egg as Mn sulfate. Experiment 2 was conducted to investigate the effect of in ovo Mn injection on the embryonic development, antioxidation and performance of offspring broilers under NT and HT. A total of 792 fertilized eggs were randomly allocated to 6 treatments in a 1 (niPC) + 1 (iNC) + 2 (injected Mn sources: Mn sulfate and Mn proteinate) × 2 (injected Mn levels: 12.5 and 25.0 μg/egg) factorial arrangement during the embryonic stage and D1 to 28 at NT. Then, 288 birds were allotted to 12 treatments in a 6 (the above embryonic treatments) × 2 (environmental temperatures: NT-22℃ vs HT-34℃) factorial arrangement from D 29 to 42. The results showed that Mn injection affected (P < 0.03) the hatchability and the maximum level of in ovo injected Mn was 25.0 μg Mn/egg. The Mn injection upregulated (P < 0.05) Mn-containing superoxide dismutase mRNA expression in the embryonic heart compared to the iNC. Hyperthermia decreased (P < 0.05) ADG and ADFI, breast muscle percentage, plsma alkaline phosphatase activity, and red color values of breast and thigh muscles, but increased (P < 0.05) F/G, plasma aspartate aminotransferase and lactic dehydrogenase activities, total cholesterol, uric acid and triiodothyronine contents, abdominal fat, light values of breast and thigh muscles of offspring broilers. The results suggest that in ovo Mn injection can enhance antioxidant ability in the chick embryonic heart.

PKCε Activation Restores Loss of PKCε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, and Microvessels in Aged and Alzheimer's Disease Hippocampus.

Vascular endothelial dysfunction and capillary loss are currently considered to be a primary phenotype of normal human aging and Alzheimer’s disease (AD). Activation of protein kinase C (PKCε) improves several molecular, cellular, physiological, and behavioral endpoints, yet it is not known whether a loss of PKCε activity occurs in the microvascular endothelium in aged and AD hippocampi, whether this loss contributes to microvascular change, or whether activation of PKCε protects against microvascular damage, an early change that induces age-associated memory defect and AD. We investigated the effect of the PKCε activation on microvascular loss in the hippocampus, important for memory storage. In cultured human brain microvascular endothelial cells, tert-butyl hydroperoxide induced oxidative stress and a decrease in manganese superoxide dismutase (MnSOD) mRNA and protein expression that were blocked by the antioxidant drugs. The PKCε activators bryostatin and DCPLA methyl ester increased PKCε, associated with an increase in MnSOD mRNA and its protein as well as vascular endothelial growth factor (VEGF), which was inhibited by the mRNA-stabilizing HuR inhibitors. In rats (>24 months old) and AD transgenic mice Tg2576 (5 months old), bryostatin or DCP-LA prevented a decrease in vascular PKCε, MnSOD, and VEGF and prevented microvascular loss and age-related memory impairment. An autopsy-confirmed AD hippocampus showed a decrease in PKCε and MnSOD mRNAs and their proteins and VEGF as well as in microvascular density compared to non-AD controls. In conclusion, the PKCε activation can rescue a decrease in PKCε, MnSOD, and VEGF via posttranscription regulation and alleviate oxidative stress, and in doing so, prevent microvascular loss during aging and AD.

Genome-wide identification of seven superoxide dismutase genes in the marine rotifer Brachionusrotundiformis and modulated expression and enzymatic activity in response to microplastics and nutritional status.

Microplastics (MPs) pollution has attracted worldwide attention. Superoxide dismutase (SOD) is a sensitive indicator for assessing the toxic effects of MPs in aquatic organisms. However, few studies have been performed to identify all genes encoding SOD in aquatic invertebrates. Especially, effects of MPs on SOD activity and expression in aquatic organisms under starvation or a subsequent refeeding status are unclear. In the present study, all full-length genes encoding SOD were cloned and characterized from the marine rotifer Brachionus rotundiformis, including CuZnSOD1, CuZnSOD2, CuZnSOD3, CuZnSOD4, CuZnSOD5, MnSOD1, and MnSOD2. The CuZnSOD1, CuZnSOD2 and MnSOD2 are homologous to SODs from vertebrates and the other SOD proteins are rotifer-specific according to the results from the phylogenetic tree. The conserved signature sequences and binding sites of Cu2+, Zn2+and Mn2+ were also identified in the seven SOD proteins. Compared with feeding, starvation down-regulated SOD activity and mRNA expression of CuZnSOD2, CuZnSOD4, CuZnSOD5, MnSOD1 and MnSOD2 while refeeding maintained SOD activity comparable to the feeding level and up-regulated CuZnSOD5 and MnSOD2. Intake of MPs by B. rotundiformis was observed by examining fluorescence signals from the fluorescently-labeled microplastics under different nutritional status. Exposure to MPs reduced rotifer density and increased malondialdehyde (MDA) content and SOD activity in the rotifers under the refeeding condition, but did not affect these indicators under the feeding and starvation conditions. However, mRNA expression of some tested genes was responsive to MPs in the fed, starved and refed rotifers. The present study for the first time demonstrated a nutritional status-dependent effect of MPs on oxidative stress response, and provided more sensitive molecular biomarkers for assessing the toxicity of MPs using B. rotundiformis as a model animal.

Taurine Prevents AFB1-Induced Renal Injury by Inhibiting Oxidative Stress and Apoptosis.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins, which can cause serious kidney damage after ingestion. Taurine protects the kidney, an effect related to its antioxidation and anti-apoptotic actions. In the present study, taurine was administered to detect the protective effect and mechanism of taurine on AFB1-induced renal injury in rats. The results show that taurine ameliorated the increase in serum blood urea nitrogen (BUN), blood creatinine (CRE), blood uric acid (UA), cystatin c (Cys-c), and urinary protein and AKP levels. Taurine also inhibits the content of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), succinate dehydrogenase (SDH), and the mRNA expression of SOD, nicotinamide adenine dinucleotide phosphate-quinine oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), and glutamate cysteine ligase catalytic (GCLC) in rat kidney tissue. The apoptotic rate of renal cells was decreased by taurine through inhibition of a mitochondrial mechanism. In summary, we found that taurine prevents AFB1-induced renal injury via enhanced antioxidant ability and mitochondrial-dependent apoptosis.

Embelin prevents amyloid-beta accumulation via modulation of SOD1 in a Streptozotocin-induced AD-like condition: An evidence from in vitro investigation.

Embelin is a neuroprotective compound with therapeutic benefit against experimental Alzheimer's disease (AD)-like condition. In the quest of untangling the underlying mechanism behind the neuroprotective effect of Embelin in AD, an in-vitro study of Embelin against neuronal damage induced by Streptozotocin (STZ) in rat hippocampal neuronal culture was performed. Current findings demonstrated that Embelin (2.5-10μM) has efficiently protected hippocampal neurons against STZ (8mM)-induced neurotoxicity. An increase in amyloid precursor protein (APP), microtubule-associated protein tau (MAPT), glycogen synthase kinase 3 alpha (GSK-3α) and glycogen synthase kinase 3 beta (GSK-3β) expression levels was observed when STZ (8mM) stimulation was done for 24h in the hippocampal neurons. A significant downregulation in the mRNA expression levels of APP, MAPT, GSK-3α, and GSK-3β upon pre-treatment with different doses of Embelin (2.5μM, 5μM and 10μM) reflects that Embelin attenuated STZ-induced dysfunction of insulin signaling (IR). Embelin significantly modulated the mRNA expression of scavenger enzyme Superoxide dismutase (SOD1). Furthermore, STZ had significantly upregulates an expression of Aβ. On the contrary, pre-treatment with three doses of Embelin reversed an Aβ-induced neuronal death. Our findings suggest that, Embelin prevents Aβ accumulation via SOD1 pathway to protect against AD-like condition.

Ellagic Acid Modulates the Amyloid Precursor Protein Gene via Superoxide Dismutase Regulation in the Entorhinal Cortex in an Experimental Alzheimer's Model.

Patients suffering from Alzheimer’s disease (AD) are still increasing worldwide. The development of (AD) is related to oxidative stress and genetic factors. This study investigated the therapeutic effects of ellagic acid (EA) on the entorhinal cortex (ERC), which plays a major role in episodic memory, in the brains of an AD rat model. AD was induced using AlCl3 (50 mg/kg orally for 4 weeks). Rats were divided into four groups: control, AD model, EA (treated with 50 mg/kg EA orally for 4 weeks), and ADEA (AD rats treated with EA after AlCl3 was stopped) groups. All rats were investigated for episodic memory using the novel object recognition test (NORT), antioxidant serum biomarkers, lipid peroxidation, histopathology of the ERC, and quantitative PCR for the superoxide dismutase (SOD) gene. EA therapy in AD rats significantly increased the discrimination index for NORT and the levels of SOD, glutathione, and total antioxidant capacity. Lipid peroxidation products were decreased, and the neurofibrillary tangles and neuritic plaques in the ERC sections were reduced after EA administration. The decrease in ERC thickness in the AD group, caused by caspase-3-mediated apoptosis and neurotoxicity due to amyloid precursor protein, was modulated by the increased SOD mRNA expression. Adjustment of the ERC antioxidant environment and decreased oxidative stress under EA administration enhanced SOD expression, resulting in the modulation of amyloid precursor protein toxicity and caspase-3-mediated apoptosis, thereby restoring episodic memory.

Natural Compounds from Hatikana Extract Potentiate Antidiabetic Actions as Displayed by In Vivo Assays and Verified by Network Pharmacological Tools.

Background Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them. Methods HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7α, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba. Results In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways. Conclusion The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation.

Insight into Seasonal Change of Phytochemicals, Antioxidant, and Anti-Aging Activities of Root Bark of Paeonia suffruticosa (Cortex Moutan) Combined with Multivariate Statistical Analysis.

Chemical compositions, antioxidants, and anti-aging activities of Cortex Moutan (CM), from different collection periods and different producing areas, were measured and compared in order to obtain excellent CM extracts. The bioactivities of CM extracts were examined by an in vitro antioxidant method and a UVB irradiated human dermal fibroblast (HDF) model. Phytochemical properties were obtained from ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS) prior to the multivariate statistical analysis. As for the results, the extracts of Heze CM (HZCM) and Luoyang CM (LYCM) collected in June had better in vitro antioxidant activities, significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA), compared to other CM extracts. HZCM and LYCM extracts could upregulate the relative expression of SOD and GSH-Px mRNA. The extract of HZCM collected in June could significantly repress the production of matrix metalloproteinase 1 (MMP-1) and improve the production of procollagen type I (PCOL)-I in UVB irradiated HDF. In total, 50 compounds, including 17 monoterpenoids, 19 flavonoids, 13 phenols, and 1 amino acid were identified or tentatively identified in the CM extracts. Gallic acid, p-hydroxybenzoic acid, oxypaeoniflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloyl glucose, and paeonol were predominant compounds in the CM extracts. Taken together, CM collected from April to September had better antioxidant and anti-aging effects for external usage.