The Anti-Inflammatory Potential of an Ethanolic Extract from Sarcopoterium spinosum Fruits for Protection and/or Counteraction against Oxidative Stress in Dysfunctional Endothelial Cells.

Plants and plant extracts are a relevant source of bioactive compounds widely employed as functional foods. In the Mediterranean area, the shrub Sarcopoterium spinosum is traditionally used as an herbal medicine for weight loss and a diabetes treatment. Inflammation is a protective mechanism involved in the development of many pathological conditions, including cardiovascular diseases. The present study aimed to investigate in vitro the antioxidant and cytoprotective properties of an ethanolic extract from S. spinosum fruits (SEE) in a cellular model of endothelium dysfunction. Corilagin and quercetin are two polyphenols abundant in SEE and were tested for comparison. The exposure of HECV cells for 24 h to 30 µM hydrogen peroxide (H2O2) lead to an oxidative stress condition. When HECV cells were treated with 10 µg/mL of SEE or single compounds after or before the oxidative insult, the results showed their ability to (i) decrease the reactive oxygen species (ROS) production quantified using fluorometric analysis and the lipid peroxidation measured with a spectrophotometric assay; (ii) rescue both the glutathione reduced to oxidized (GSH/GSSG) ratio and nitric oxide impair and the protein denaturation; and (iii) accelerate the wound repair measured using a T-scratch assay. Taken together, our findings indicate that the ethanolic extract from S. spinosum fruits could be a potential candidate for nutraceutical application.

In-vivo and in-silico studies to identify toxicity mechanisms of permethrin with the toxicity-reducing role of ginger.

In this study, the toxic effects of permethrin on Allium cepa L. and the protective role of Zingiber officinale rhizome extract (Zoex) were investigated. In this context, 6 different groups were formed. While the control group was treated with tap water, the groups II and III were treated with 10 µg/mL and 20 µg/mL Zoex, respectively, and the group IV was treated with 100 µg/L permethrin. The protective effect of Zoex against permethrin toxicity was studied as a function of dose, and groups V and VI formed for this purpose were treated with 10 µg/mL Zoex + 100 µg/L permethrin and 20 µg/mL Zoex + 100 µg/L permethrin, respectively. After 72 h of germination, cytogenetic, biochemical, physiological, and anatomical changes in meristematic cells of A. cepa were studied. As a result, permethrin application decreased the mitotic index (MI) and increased the frequency of micronuclei (MN), and chromosomal abnormalities. The increase in malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) and the decrease in glutathione (GSH) indicate that permethrin causes oxidative damage. Compared to the control group, a 68.5% decrease in root elongation (p < 0.05) and an 81.8% decrease (p < 0.05) in weight gain were observed in the permethrin-treated group. It was found that the application of Zoex together with permethrin resulted in regression of all detected abnormalities, reduction in the incidence of anatomical damage, MN and chromosomal aberrations, and improvement in MI rates. The most significant improvement was observed in group VI treated with 20 µg/mL Zoex, and Zoex was also found to provide dose-dependent protection. The toxicity mechanism of permethrin was also elucidated by molecular docking and spectral studies. From the data obtained during the study, it was found that permethrin has toxic effects on A. cepa, a non-target organism, while Zoex plays a protective role by reducing these effects.

The nonessential amino acid cysteine is required to prevent ferroptosis in acute myeloid leukemia.

ABSTRACT: Cysteine is a nonessential amino acid required for protein synthesis, the generation of the antioxidant glutathione, and for synthesizing the nonproteinogenic amino acid taurine. Here, we highlight the broad sensitivity of leukemic stem and progenitor cells to cysteine depletion. By CRISPR/CRISPR-associated protein 9-mediated knockout of cystathionine-γ-lyase, the cystathionine-to-cysteine converting enzyme, and by metabolite supplementation studies upstream of cysteine, we functionally prove that cysteine is not synthesized from methionine in acute myeloid leukemia (AML) cells. Therefore, although perhaps nutritionally nonessential, cysteine must be imported for survival of these specific cell types. Depletion of cyst(e)ine increased reactive oxygen species (ROS) levels, and cell death was induced predominantly as a consequence of glutathione deprivation. nicotinamide adenine dinucleotide phosphate hydrogen oxidase inhibition strongly rescued viability after cysteine depletion, highlighting this as an important source of ROS in AML. ROS-induced cell death was mediated via ferroptosis, and inhibition of glutathione peroxidase 4 (GPX4), which functions in reducing lipid peroxides, was also highly toxic. We therefore propose that GPX4 is likely key in mediating the antioxidant activity of glutathione. In line, inhibition of the ROS scavenger thioredoxin reductase with auranofin also impaired cell viability, whereby we find that oxidative phosphorylation-driven AML subtypes, in particular, are highly dependent on thioredoxin-mediated protection against ferroptosis. Although inhibition of the cystine-glutamine antiporter by sulfasalazine was ineffective as a monotherapy, its combination with L-buthionine-sulfoximine (BSO) further improved AML ferroptosis induction. We propose the combination of either sulfasalazine or antioxidant machinery inhibitors along with ROS inducers such as BSO or chemotherapy for further preclinical testing.

Chloride, glutathiones, and insect-derived elicitors introduced into the xylem trigger electrical signaling.

Ricca assays allow the direct introduction of compounds extracted from plants or the organisms that attack them into the leaf vasculature. Using chromatographic fractionation of Arabidopsis (Arabidopsis thaliana) leaf extracts, we found glutamate was the most active low mass elicitor of membrane depolarization. However, other known elicitors of membrane depolarization are generated in the wound response. These include unstable aglycones generated by glucosinolate (GSL) breakdown. None of the aglycone-derived GSL-breakdown products, including nitriles and isothiocyanates, that we tested using Ricca assays triggered electrical activity. Instead, we found that glutathione and the GSL-derived compound sulforaphane glutathione triggered membrane depolarizations. These findings identify a potential link between GSL breakdown and glutathione in the generation of membrane depolarizing signals. Noting that the chromatographic fractionation of plant extracts can dilute or exchange ions, we found that Cl- caused glutamate receptor-like3.3-dependent membrane depolarizations. In summary, we show that, in addition to glutamate, glutathione derivatives as well as chloride ions will need to be considered as potential elicitors of wound-response membrane potential change. Finally, by introducing aphid (Brevicoryne brassicae) extracts or the flagellin-derived peptide flg22 into the leaf vasculature we extend the use of Ricca assays for the exploration of insect/plant and bacteria/plant interactions.

Boosting Reactive Oxygen Species Generation with a Dual-Catalytic Nanomedicine for Enhanced Tumor Nanocatalytic Therapy.

Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO2 and dihydroartemisinin (DHA) (LIPSe@CuO2&DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H2O2 and Cu2+, CuO2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H2O2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu2+-to-Cu+ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO2&DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.

Biomarkers of oxidative stress in broiler chickens attacked by lipopolysaccharide: A systematic review and meta-analysis.

Oxidative stress (OS) constitutes a pivotal factor in the initiation and progression of lipopolysaccharide (LPS) challenges in broiler chickens. Increasing studies have demonstrated that Alleviation of oxidative stress seems to be a reasonable strategy to alleviate LPS-mediated afflictions in broilers. Nonetheless, the relationship between OS-related indicators and exposure to LPS remains a topic of debate. The aim of this investigation was to precisely and holistically evaluate the effect of LPS exposure on OS-associated markers. We conducted a systematic search of four electronic databases-PubMed, Web of Science, Scopus, and Cochrane for relevant studies, and a total of 31 studies were included. The overall results showed that the LPS treatment significantly increased the levels of oxygen radicals and their products, such as malondialdehydes (MDA), reactive oxygen species (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG), while significantly reduced the levels of antioxidants, such as total antioxidative capacity (T-AOC), total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH), in the chickens. Intriguingly, though the observed trends in alterations were not strictly correlated with LPS concentrations, the enzyme activity levels were indeed influenced by the concentration of LPS. This observation highlights the complex relationship between LPS exposure and the body's antioxidant response. Despite some limitations, all the included studies were deemed credible. Subgroup evaluations revealed that the jejunum and duodenum has demonstrated stronger antioxidant capability compared to other tissues. Overall, our study presents compelling evidence that exposure to LPS induces significant OS in chickens. And we also found that the extent of OS was related to LPS doses, target tissues, and dietary ingredients.

Improvement of diluted semen from Muscovy (Cairina moschata) drakes by the addition of water-soluble antioxidants.

The aim of this study was to evaluate the effect of antioxidant supplementation in diluted semen from Muscovy drakes after the induction of oxidative stress (OS) on the sperm motility, kinematic parameters and biochemical markers - lipid peroxidation (LPO) levels and total glutathione (tGSH) concentration. The pooled semen was distributed equally into three parts, diluted (1:3 v/v) with IMV Canadyl, HIA-1 or AU, and stored at 4°C for 6 h. Later, the semen was equilibrated at 20-25°C for 15 min, and divided in Eppendorf tubes. The sperm samples (final concentration of 50 × 106 sperm cells/mL per sample) were incubated at 37°C for 30 min in the absence (-) or presence (+) of 0.1 mM FeSO4 + 0.5 mM H2 O2 (Fenton system) and the following combinations of antioxidants: ascorbic acid + Trolox (A + T); ascorbic acid + Desferal (A + D); Trolox + Desferal (T + D) and ascorbic acid + Trolox + Desferal (A + T + D), all of them in a final concentration of 0.1 mM. Thus, the total number of samples was 30 and in each one, the sperm motility, velocity parameters, LPO and tGSH were determined. The motility and kinematic parameters of the diluted semen with added antioxidants were restored by up to 20% after inducing OS via the Fenton reaction. Dual combinations of antioxidants (A + T, A + D, and T + D) lowered LPO levels, but not equally across different extenders. After the induction of OS, the tGSH levels in diluted semen with IMV-Canadyl were not affected by the added antioxidants. Whereas antioxidant combinations in diluted semen with HIA-1 or AU had a beneficial effect and partially restored tGSH levels. In conclusion, the results showed that the extender IMV-Canadyl is well balanced and protected the Muscovy semen under OS conditions, while the other two extenders HIA-1 and AU can be improved by adding antioxidants.

Mn2+ /Ir3+ -Doped and CaCO3 -Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image-Guided Synergistic Cancer Therapy.

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

N-acetylcysteine improves the inhibitory effect of Quercetin-rich onion extract on HT-29 and HCT-116 colorectal cancer migration and invasion through iNOS suppression.

As colorectal cancer (CRC) usually presents at an advanced stage, it responds poorly to traditional surgery and chemoradiotherapy. Reactive oxygen species (ROSs) are a critical factor in cancer progression. Quercetin, a bioflavonoid derived from onion peel extract, provides great anti-oxidant and anti-cancer potential. Therefore, quercetin in combination with N-Acetylcysteine (NAC), a well-known anti-oxidant and adjuvant agent in cancer-chemotherapeutic drugs, was considered as a way of increasing treatment efficacy. Thus, this study aimed to evaluate the improvement effect of quercetin in combination with NAC in human CRC (HT-29 and HCT-116) cell progression, migration and invasion. Firstly, the effects of quercetin, NAC, and the combination of quercetin and NAC on cellular oxidants and glutathione levels were evaluated. Cell viability, anti-migrative activity and invasive activity were determined by MTT, wound healing, and Matrigel invasion tests, respectively. Then, the proteins involved in cell migration, invasion, and cellular oxidants were investigated. Moreover, the gene expression and overall survival were further validated by the GEPIA2 database. The results reveal that the combination was most effective in decreasing cellular oxidants and increasing glutathione levels, while there was a significant decrease in cancer cell migration and invasion involved in the suppression of iNOS, ICAM-1, and MMP-2 proteins. Furthermore, bioinformatic analysis verified that iNOS, ICAM-1, and MMP-2 were highly expressed in CRC tissue and also associated with a poor prognosis. This study demonstrated that Quercetin has higher efficacy when used in combination with NAC, representing a potential combination agent for anti-cancer drug development.

The Therapeutic Effect of Silymarin and Silibinin on Depression and Anxiety Disorders and Possible Mechanism in the Brain: A Systematic Review.

BACKGROUND: Depression and anxiety are the most common mental disorders worldwide. OBJECTIVE: We aimed to review silymarin and silibinin effects and underlying mechanisms in the central nervous system (CNS) for depression and anxiety treatment. METHODS: The research protocol was prepared based on following the PRISMA statement. An extensive search was done in essential databases such as PubMed, Cochrane Library, Web of Science (ISI), Embase, and Scopus. Considering the study inclusion and exclusion criteria, 17 studies were finally included. The desired information was extracted from the studies and recorded in Excel, and the consequences and mechanisms were reviewed. RESULTS: Silymarin and silibinin upregulated brain-derived neurotrophic factor (BDNF) and improved neural stem cells (NSCs) proliferation in the cortex and hippocampus. They also increased neurochemical serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels. Silymarin and silibinin reduced malondialdehyde (MDA) formation and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. In addition, silymarin and silibinin reduced interleukin (IL)-6, IL-1ß, and IL-12ß, reducing tumor necrosis factor α (TNF-α) induced neuroinflammation. CONCLUSION: Silymarin and silibinin exert anti-depression and anxiolytic effects by regulating neurotransmitters, endocrine, neurogenesis, and immunologic systems. Therefore, as natural and complementary medicines, they can be used to reduce the symptoms of depression and anxiety; However, more clinical studies are needed in this field.

Polysaccharide isolated from wax apple suppresses ethyl carbamate-induced oxidative damage in human hepatocytes. / èŽ²é›¾å¤šç³–å¯¹æ°¨åŸºç”²é ¸ä¹™é ¯è¯±å¯¼äººè‚ç»†èƒžæ°§åŒ–æŸä¼¤çš„æŠ‘åˆ¶ä½œç”¨ç ”ç©¶.

Wax apple (Syzygium samarangense) has received growing research interest for its high nutritional and medicinal value due to its constituents such as polysaccharide, organic acids, flavonoids, minerals, and other substances. In this study, wax apple polysaccharide (WAP) was isolated from this plant and its protective effect against ethyl carbamate (EC)|-induced oxidative damage was evaluated in human hepatocytes (L02 cells). Firstly, a series of analyses such as high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FT-IR), gas chromatography/mass spectrometry (GC/MS), and 1H and 13C nuclear magnetic resonance (NMR) were conducted to identify the structure of WAP. Thereafter, in vitro cell experiments were performed to verify the protective effects of WAP against EC-induced cytotoxicity, genotoxicity, and oxidative damage in L02 cells. Our results revealed that WAP is composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose in a molar ratio of 2.20:|3.94:|4.45:|8.56:|8.86:|30.82:|39.78:|1.48. Using a combination of methylation and NMR spectroscopic analysis, the primary structure of WAP was identified as Araf-(1→, Glcp-(1→, →2)|-Araf-(1→, →3)|-Galp-(1→, →3)|-Araf-|(1→, and →6)|-Galp-|(1→. Cell experiments indicated that WAP exhibited significant protective effects on EC-treated L02 cells via suppressing cytotoxicity and genotoxicity, reducing reactive oxygen species (ROS) and O2•- formation, as well as improving mitochondrial membrane potential (MMP) and glutathione (GSH). In a nutshell, WAP has the potential as an important therapeutic agent or supplement for hepatic oxidative damage. Meanwhile, further studies are needed to prove the above effects in vivo at the biological and clinical levels.

Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis.

AIM: N-acetylcysteine (NAC), a thiol-containing antioxidant and glutathione (GSH) precursor, attenuates oxidative stress, and possibly improves psychiatric disorders. This study aimed to evaluate the effects of oral NAC on oxidative stress, depression, and anxiety symptoms in patients with multiple sclerosis (MS). METHODS: This clinical trial was conducted on 42 MS patients randomly assigned to intervention (n = 21) and control (n = 21) groups. The intervention group received 600 mg of NAC twice daily for 8 weeks, and the control group received a placebo with the same prescription form. An analysis of serum malondialdehyde (MDA), serum nitric oxide (NO), and erythrocyte GSH was carried out on both groups, along with a complete blood count. The Hospital Anxiety and Depression Scale (HADS) was used to assess symptoms of depression (HADS-D) and anxiety (HADS-A). RESULTS: Compared to the control group, NAC consumption significantly decreased serum MDA concentrations (-0.33 [-5.85-2.50] vs. 2.75 [-0.25-5.22] µmol/L; p = 0.03) and HADS-A scores (-1.6 ± 2.67 vs. 0.33 ± 2.83; p = 0.02). No significant changes were observed in serum NO concentrations, erythrocyte GSH levels, and HADS-D scores (p > 0.05). CONCLUSIONS: Based on the findings of the present study, NAC supplementation for 8 weeks decreased lipid peroxidation and improved anxiety symptoms in MS patients. The aforementioned results suggest that adjunctive therapy with NAC can be considered an effective strategy for MS management. Further randomized controlled studies are warranted.

Dietary glutathione supplementation attenuates oxidative stress and improves intestinal barrier in diquat-treated weaned piglets.

The aim of this study was to investigate the protective effects of glutathione (GSH) against oxidative stress and intestinal barrier disruption caused by diquat (an oxidative stress inducer) in weaned piglets. Twenty-four piglets were randomly assigned to four treatments with six pigs per treatment for an 18-d trial. Treatments were basal diet, basal diet + diquat challenge, 50 mg/kg GSH diets + diquat challenge and 100 mg/kg GSH diets + diquat challenge. On day 15, piglets in basal diet group and diquat-challenged groups were intraperitoneally injected with sterile saline and diquat at 10 mg/kg body weight, respectively. The results showed that GSH supplementation improved growth performance of diquat-injected piglets from days 15 to 18 (p < 0.05), especially at a dose of 100 mg/kg GSH. Meanwhile, diquat also caused oxidative stress and intestinal barrier damage in piglets. However, GSH supplementation enhanced the antioxidant capacity of serum and jejunum, as evidenced by the increase in GSH content and total superoxide dismutase activities and the decrease in 8-hydroxy-2'-deoxyguanosine concentrations (p < 0.05). GSH also up-regulated the mRNA expressions of intestinal tight junction protein (zonula occludens 1, ZO1; occludin, OCLN; claudin-1, CLDN1) and mitochondrial biogenesis and function (peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, PGC1α; mitochondrial transcription factor A, TFAM; cytochrome c, CYCS), compared with diquat-challenged piglets in basal diet (p < 0.05). Thus, the study demonstrates that GSH protects piglets from oxidative stress caused by diquat and 100 mg/kg GSH has a better protective role.

Reducing oxidative stress by κ-carrageenan and C60HyFn: The post-thaw quality and antioxidant status of Azari water buffalo bull semen.

Azeri water buffalo is a species of great interest due to the high quality of its products such as milk. Due to the decreasing trend of its number and risk of extinction in the future, our attention is directed towards ensuring the preservation of its genetic reserves by keeping its sperm. Using antioxidants in semen extender is one of the ways to reduce the detrimental effects of freezing process on post-thawed quality of spermatozoa. This study was conducted to determine the effect of κ-carrageenan (k-CRG) and C60HyFn supplemented semen extender on the quality of post-thawed Azari water buffalo spermatozoa. A total of 30 semen samples were obtained from three buffaloes using an artificial vagina (twice a week for five weeks = 10 replicates). The samples (n = 3) from each replicate were pooled and divided into equal aliquots to prepare 14 extender groups, including control (C), k-0.2, K-0.4, K-0.6, K-0.8 (containing 0.2, 0.4, 0.8 mg K-CRG/mL, respectively), C-0.1, C-0.2, C-0.4, C-0.8, C-1, C-5, C-10, C-20, and C-40 (containing 0.1, 0.2, 0.4, 0.6, 0.8, 1, 5, 10, 20, 40 µM C60HyFn, respectively), and then frozen. After thawing, motility and velocity parameters, plasma membrane integrity (PMI) and functionality (PMF), DNA damage, Hypo-osmotic swelling (HOS) test, malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase glutathione activities and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging were evaluated. In vivo fertility was compared between k-0.6, C-1 and control groups. 60 buffalo were inseminated 24 h after the onset of estrus. The diagnosis of pregnancy was performed rectally at least 60 days after fertilization. Total and progressive motility and velocity parameters were improved by k-0.4, k-0.6, k-0.8, C-0.4, C-0.8, C-1, C-5, and C-10 groups) compared to the other groups. Plasma membranes integrity and PMF were improved by k-0.4, k-0.6, C-0.4, C-0.8, C-1, C-5, and C-10 groups compared to other groups, while in terms of sperm DNA damage K-0.4, K-0.6, K-0.8, C-0.2, C-0.4, C-0.8, C-1, C-5, and C-10 groups showed better results compared to the control group. The evidence also showed that k- 0.4, k-0.6, k-0.8, C-0.4, C-0.8, C-1, C-5, and C-10 groups could improve TAC, and decrease MDA levels. Also, k-0.4, k-0.6, k-0.8, C-0.2, C-0.4, C-0.8, C-1, C-5, and C-10 groups could improve GPx, CAT, and GSH levels, but no significant difference was found regarding SOD compared to the other groups. DPPH scavengers were tested by K-0.6, K-0.8 and C-1, C-5, C-10, C-0.8, C-0.4 and C-0.2 groups and compared to other groups improved. The fertility rate [70% (14/20)] was higher in C-1 than other groups. To conclude that k-CRG and C60HyFn supplementation can increase the quality parameters of cryopreserved buffalo semen after thawing and that 1 M C60HyFn can increase in vivo fertility of buffalo semen.

Attenuating effects of selenium and zinc against hexavalent chromium-induced oxidative stress, hormonal instability, and placenta damage in preimplanted rats.

As a toxic metal, hexavalent chromium (CrVI) has effects on both the reproductive and endocrine systems. This study aimed to evaluate the protective effects of selenium (Se) and zinc (Zn) against the toxicity of chromium on the placenta in pregnant Wistar albino rats. Thirty pregnant Wistar rats were divided into control and four treated groups, receiving subcutaneously (s.c) on the 3rd day of pregnancy, K2Cr2O7 (10 mg/kg body weight (bw)) alone, or in association with Se (0.3 mg/kg bw), ZnCl2 (20 mg/kg bw), or both of them simultaneously. Plasma steroid hormones, placenta histoarchitecture, oxidative stress profile, and developmental parameters were investigated. These results showed that K2Cr2O7 exposure induced a significant increase in the levels of both plasma estradiol (E2) and placenta malondialdehyde (MDA), the number of fetal resorptions, and percent of post-implantation loss. On the other hand, K2Cr2O7 significantly reduced developmental parameters, maternal body and placenta weight, and plasma progesterone (P) and chorionic gonadotropin hormone (ß HCG) levels. However, K2Cr2O7 significantly decreased the placenta activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and nonprotein sulfhydryl (NPSH). These changes have been reinforced by histopathological evaluation of the placenta. Se and/or ZnCl2 supplementation provoked a significant improvement in most indices. These results suggest that the co-treatment with Se or ZnCl2 strongly opposes the placenta cytotoxicity induced by K2Cr2O7 through its antioxidant action.

Mechanisms of action of non-enzymatic antioxidants to control oxidative stress during in vitro follicle growth, oocyte maturation, and embryo development.

In vitro follicle growth and oocyte maturation still has a series of limitations, since not all oocytes matured in vitro have the potential to develop in viable embryos. One of the factors associated with low oocyte quality is the generation of reactive oxygen species (ROS) during in vitro culture. Therefore, this review aims to discuss the role of non-enzymatic antioxidants in the control of oxidative stress during in vitro follicular growth, oocyte maturation and embryonic development. A wide variety of non-enzymatic antioxidants (melatonin, resveratrol, L-ascorbic acid, L-carnitine, N-acetyl-cysteine, cysteamine, quercetin, nobiletin, lycopene, acteoside, mogroside V, phycocyanin and laminarin) have been used to supplement culture media. Some of them, like N-acetyl-cysteine, cysteamine, nobiletin and quercetin act by increasing the levels of glutathione (GSH), while melatonin and resveratrol increase the expression of antioxidant enzymes and minimize oocyte oxidative stress. L-ascorbic acid reduces free radicals and reactive oxygen species. Lycopene positively regulates the expression of many antioxidant genes. Additionally, L-carnitine protects DNA against ROS-induced damage, while acteoside and laminarin reduces the expression of proapoptotic genes. Mogrosides increases mitochondrial function and reduces intracellular ROS levels, phycocyanin reduces lipid peroxidation, and lycopene neutralizes the adverse effects of ROS. Thus, it is very important to know their mechanisms of actions, because the combination of two or more antioxidants with different activities has great potential to improve in vitro culture systems.

The effects of melatonin, glutathione and vitamin E on semen cryopreservation of Mediterranean buffalo.

The aim of this study was to investigate the effects of melatonin (MLT), reduced glutathione (GSH) and vitamin E (Vit. E) or their combinations on semen cryopreservation of Mediterranean buffalo. The quality parameters such as viability, abnormality rate, motility, structural integrity and the antioxidant capacity of frozen-thawed sperm were evaluated. The efficiency of frozen-thawed sperms in performing their functions was further analyzed by in vitro fertilization (IVF). In those separately supplemented groups, 0.2 mg/mL MLT, 0.2 mM GSH and 0.4 mg/mL Vit. E had the best effect on antioxidant capacity, kinetics and morphology, respectively. In addition, the cleavage, blastocyst and hatching blastocyst rates of IVF embryos were higher in 0.2 mg/mL MLT, 0.2 mM GSH, 0.2 and 0.4 mg/mL Vit. E groups than the blank control. Among the three combination groups, the kinetics and structure integrity of frozen-thawed sperms, cleavage, blastocyst and hatching blastocyst rates of IVF embryos were higher in 0.4 mg/mL Vit. E plus 0.2 mg/mL MLT group than the blank control group, revealed that this combination had comprehensive protection on frozen-thawed sperm of Mediterranean buffalo. These results support to develop special semen freezing extender containing an optimal choice of MLT, GSH and Vit. E, and to enhance the efficiency of frozen-thawed sperm of Mediterranean buffalo for IVF.

Pre-clinical investigation of protective effect of nutraceutical D-glucosamine on TNBS-induced colitis.

OBJECTIVE: The level of precursors involved in the biosynthesis of glycosaminoglycan (GAG), glucosamine synthase, and N-acetyl glucosamine (NAG), are significantly reduced in inflammatory bowel disease (IBD). This results in deficient GAG content in mucosa, which eventually disrupt the gut wall integrity, provoking abnormal immunological responses. This is characterized by colossal liberation of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukins (ILs), and reactive oxygen species (ROS) provoking colonic inflammation. D-glucosamine (D-GLU) is reported to suppress oxidative stress, and pro-inflammatory cytokines and acts as a starting material for biosynthesis of NAG. The potential of D-GLU and its combination with mesalamine (5-ASA) was investigated in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-instigated IBD in Wistar rats. MATERIALS AND METHODS: Standard and test drugs were given orally for 5 d to separate groups of rats. Colonic inflammation was evaluated by disease activity score rate (DASR), colon/body weight ratio, colon length, diameter, colon pH, histological injury, and score. Inflammatory biomarkers IL-1ß, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed. RESULTS: Combination of D-GLU + 5-ASA significantly ameliorated severity of colonic inflammation by lowering DASR (p < 0.001) and colon/body weight ratio (p < 0.001), restored the colonic architecture and suppressed the histopathological score (p < 0.001), along with the absence of major adverse reactions. The combination suppressed the levels of inflammatory markers (p < 0.001) and MDA (p < 0.001) while enhancing GSH level (p < 0.001). CONCLUSION: In comparison to individual 5-ASA and D-GLU, combination of drugs significantly diminished colitis severity through their combined anti-inflammatory and antioxidant effects by acting on multiple targets simultaneously. The combination holds remarkable potential in the management of IBD.

Liver protection and hemostatic effects of medicinal plant Arnebia euchroma (Royle) I.M.Johnst extract in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Arnebia euchroma (Royle) I.M.Johnst. (AE) is a Chinese medicinal herb that is traditionally used to treat various circulatory diseases. It exhibits certain effects, such as the promotion of blood circulation and cooling, rash clearance, and detoxification. AIM OF THE STUDY: This study was designed to explore the hepatoprotective and hemostatic effects of the ethyl acetate extract of AE in rats with carbon tetrachloride (CCl4)-induced liver injury. MATERIALS AND METHODS: Wistar rats were treated via oral gavage with different doses of the ethyl acetate extract of AE (3.5, 7, or 14 g kg-1·day-1) for 14 consecutive days, following which hemostatic and liver function tests were conducted. For the hemostatic tests, the platelet count, blood platelet aggregation, blood platelet adhesion to fibrinogen, platelet factor 4 (PF-4) secretion from blood platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen levels were measured at the end of the treatment period. For the liver function tests, 0.25 mL/200 g (1.25 mL kg-1·day-1) of olive oil was injected into the abdominal cavity of the control rats, whereas 15% CCl4 plus olive oil (prescription: 7.5 mL CCl4 + 42.5 olive oil) was injected into that of the treated rats at 1 h after extract administration on day 6, 13, and 20. Additionally, food and water were withheld from all the animals. On the following day, the rats were anesthetized and their albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), reactive oxygen species (ROS), methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. Glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx) levels among the groups were determined using a one-way analysis of variance. RESULTS: The platelet count and blood platelet aggregation, blood platelet adhesion to fibrinogen and PF-4 secretion levels were significantly increased in the (3.5 g kg-1 day-1) AE group as compared to those in the control group (all p < 0.001; for the 7 and 14 g kg-1 day-1 AE groups, all p > 0.05, respectively). Although the PT and aPTT were not affected by the AE extract (all p > 0.05), the TT was reduced and the FIB levels were significantly increased in all AE groups (p < 0.05). Liver function tests showed that CCl4 caused significant liver damage, thereby decreasing the albumin, SOD, CAT, GSH, GST, GR, and GPx levels, while increasing the AST, ALT, ALP, SGOT, SGPT, GGT, LDH, ROS, and MDA levels (all p < 0.001). By contrast, treatment with the different doses of AE extract reversed the CCl4 effects on all these parameters. Compared with the levels in the CCl4 group, the GSH and GR levels in the three AE groups (3.5, 7, and 14 g kg-1·day-1) were significantly higher (p < 0.05, p < 0.01, and p < 0.001, respectively), whereas the differences in the other parameters for these three groups were all at the significance levels of p < 0.05, p < 0.05, and p < 0.01, respectively. CONCLUSIONS: AE extracts administered orally exhibited hepatoprotective activity by affecting platelet production and blood coagulation and ameliorating liver function-damaging modifications. Specifically, a dosage of 3.5 g kg-1·day-1 resulted in the most optimal effects.

GC-MS and HPLC supported phytochemical analysis of watercress and the protective role against paraben toxicity.

In this study, the phytochemical content of Nasturtium officinale R. Br. (watercress) leaf extract (Noex) and its protective effects against paraben toxicity were investigated. GC-MS and HPLC analyses were performed to determine the phytochemical content. Paraben toxicity and protective properties of Noex were investigated with the Allium test, and 6 different groups were formed for this purpose. Toxicity in each group was investigated by using physiological, cytogenetic, biochemical, and anatomical parameters. DNA-paraben interaction was investigated with spectroscopic analysis for the genotoxicity mechanism. As a result of the study, paraben (500 mM) caused a regression in the physiological parameters related to germination in Allium cepa L. bulbs. Paraben caused a 43.3% reduction in mitotic index (MI) rates compared to control, which is likely the reason for the decrease in germination-related parameters. With the application of paraben in root tip cells, the frequency of micronucleus (MN) and chromosomal aberrations (CAs) increased and a high genotoxic effect was observed. Paraben promoted CAs such as fragment, sticky chromosome, bridge, unequal distribution of chromatin, and irregular mitosis. It also caused anatomical damage in the form of epidermis cell damage, flattened cell nucleus, cortex cell damage, cortex cell walls thickening, and unclear vascular tissue in root tip meristem cells. Paraben-DNA interaction was caused by bathochromic and hypochromic shifts in the UV spectrum of DNA, indicating the intercalation mode of interaction. Paraben also caused an increase in malondialdehyde (MDA) levels, a decrease in glutathione (GSH) levels, and abnormalities in antioxidant enzyme levels (superoxide dismutase = SOD and catalase = CAT), thereby disrupting the antioxidant/oxidant dynamics in the cell. The basis of physiological, cytological, and genetic abnormalities was attributed to the oxidative stress in the cell. Administration of Noex produced a dose-dependent incremental improvement in paraben-induced abnormalities. The increase in GSH levels and the decrease in MDA levels observed as a result of the Noex application contributed to the restoration of antioxidant/oxidant balance, and this improvement was also reflected in other parameters. Application of 200 mg/L Noex provided a 24.2% improvement in the MI rate reduced by paraben, and accordingly, an increase in germination parameters was observed. Similarly, the frequencies of MN and CAs, which are signs of genotoxicity, decreased with the Noex application. As a result of the phytochemical analysis of Noex with HPLC and GC-MS, the presence of strong antioxidant and antimutagenic substances such as rutin, coumaric acid, ferrulic acid, L-serine, L-proline, and phytol were determined in Noex structure. The curative effects of Noex against paraben toxicity can be attributed to these active ingredients.