Effect of gallic acid on the reproduction of adolescent male Brandt’s vole (Lasiopodomys brandtii)

2021 ◽  
Author(s):  
Xin Dai ◽  
Xiao-Feng Sun ◽  
Ai-Qin Wang ◽  
Wanhong Wei ◽  
Sheng-Mei Yang
Keyword(s):  
Gallic Acid ◽  
Low Dose ◽  
Regulatory Protein ◽  
Antioxidant Properties ◽  
Adolescent Male ◽  
Seminiferous Tubules ◽  
High Dose ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Lasiopodomys Brandtii

Gallic acid (GA), a phenol that is present in various plants, potentially contains antioxidant properties. This study aimed to investigate the effects of GA on the reproduction of adolescent male Brandt’s voles (Lasiopodomys brandtii (Radde, 1861)). Antioxidant levels and apoptosis in the testis, as well as reproductive physiology, were evaluated in adolescent males treated with GA. The results showed that a low dose of GA enhanced relative epididymis weight and the sperm density in the epididymis, increased the mRNA levels of steroidogenic acute regulatory protein in the testis, and reduced the percentages of abnormal and dead sperm. In addition, a low dose of GA significantly increased the levels of superoxide dismutase, catalase, and glutathione peroxidase, and decreased the level of malondialdehyde in the testis, as well as the mRNA and protein levels of the apoptosis related gene, caspase-3. However, a high dose of GA sharply reduced the average diameter of the seminiferous tubules compared to a low dose. Collectively, these findings demonstrate that GA treatment during puberty affects the reproductive responses of male Brandt’s voles in a dose-dependent manner by regulating antioxidant levels and apoptosis.

scholarly journals Reproductive responses of the male Brandt’s vole, Lasiopodomys brandtii (Rodentia: Cricetidae) to tannic acid

2020 ◽  
Vol 37 ◽  
pp. 1-11
Author(s):  
Xin Dai ◽  
Ling-Yu Zhou ◽  
Ting-Ting Xu ◽  
Qiu-Yue Wang ◽  
Bin Luo ◽  
...  
Keyword(s):  
Tannic Acid ◽  
Low Dose ◽  
Mrna Level ◽  
Regulatory Protein ◽  
Antioxidant Properties ◽  
Sperm Concentration ◽  
High Dose ◽  
Mrna Levels ◽  
Pubertal Stage ◽  
Lasiopodomys Brandtii

Tannins are polyphenols that are present in various plants, and potentially contain antioxidant properties that promote reproduction in animals. This study investigated how tannic acid (TA) affects the reproductive parameters of male Brandt’s voles, Lasiopodomys brandtii (Radde, 1861). Specifically, the anti-oxidative level of serum, autophagy in the testis, and reproductive physiology were assessed in males treated with TA from the pubertal stage. Compared to the control, low dose TA enhanced relative testis and epididymis weight and sperm concentration in the epididymis, and significantly increased the level of serum superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). mRNA levels of autophagy related genes LC3 and Beclin1 decreased significantly with low dose TA compared to the control. However, compared to the control, high dose TA sharply reduced the levels of serum SOD, GSH-Px, CAT, serum testosterone (T), and mRNA level in steroidogenic acute regulatory protein (StAR) in the testis. Both sperm abnormality and mortality increased with high dose TA compared to the control and low dose TA. Collectively, this study demonstrated that TA treatment during puberty had a dose-dependent effect on the reproductive responses of male Brandt’s voles. TA might mediate autophagy in the testis, through both indirect and direct processes. TA mainly affected the reproductive function of male Brandt’s voles by regulating anti-oxidative levels. This study advances our understanding of the mechanisms by which tannins influence reproduction in herbivores.

scholarly journals Icariin Restores Bone Structure and Strength in a Rat Model of Chronic High-Dose Alcohol-Induced Osteopenia

2018 ◽  
Vol 46 (4) ◽  
pp. 1727-1736 ◽  
Author(s):  
Jie-Zhou Wu ◽  
Peng-Cheng Liu ◽  
Run Liu ◽  
Ming Cai
Keyword(s):  
Mechanism Of Action ◽  
Rat Model ◽  
Low Dose ◽  
Bone Structure ◽  
Biomechanical Properties ◽  
High Dose ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Alcohol Group

Background/Aims: Chronic alcohol abuse is an important risk factor for osteopenia. However, few studies have focused on the efficacy and mechanism of action of icariin on alcohol-induced osteopenia. The aim of this study was to investigate the efficacy and underlying mechanism of action of icariin in the treatment of chronic high-dose alcohol-induced osteopenia in a rat model. Methods: Thirty-six adult male Sprague-Dawley rats were randomly divided into four groups: sham, alcohol, and low-dose and high-dose icariin groups. Bone volume fraction (BV/TV), bone mineral density (BMD), bone biomechanical properties, and bone morphology were assessed after 16 weeks. Reverse-transcription PCR was used to detect mRNA expression levels of alkaline phosphatase (ALP), collagen type I (Col I), osteocalcin (OC), runt-related transcription factor 2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteoprotegerin (OPG). Results: Bone metabolic markers and biomechanical properties in the alcohol group were decreased significantly compared with the sham group. BV/TV, BMD, mineral apposition rate (MAR), percent trabecular area (%Tb.Ar), and bone biomechanical properties were elevated in the low-dose and high-dose icariin groups relative to the alcohol group. ALP, Col I, OC, Runx2, BMP-2, and OPG mRNA levels in the icariin group were significantly elevated in comparison with the alcohol group. Conclusion: Icariin can prevent overall progression of chronic high-dose alcohol-induced osteopenia in a rat model, in a dose-dependent manner. Icariin promotes bone formation and inhibits bone loss, and effectively restores bone structure and strength in chronic high-dose alcohol-induced osteopenic rats. Bone metabolism reversal is evidenced by increased BV/TV, BMD, MAR, %Tb.Ar, and biomechanical properties and elevated ALP, Col I, OC, Runx2, BMP-2, and OPG mRNA levels.

Calcitriol Exerts Prophylactic Anti-Mycobacterium Effect In A Dose-Dependent Manner

2021 ◽  
Author(s):  
Jianguo Li ◽  
Zhen Li ◽  
Zefeng Gao ◽  
Juan Xia ◽  
Jia Cui ◽  
...  
Keyword(s):  
Vitamin D ◽  
1H Nmr ◽  
Low Dose ◽  
Bacterial Load ◽  
High Dose ◽  
Dependent Manner ◽  
Prophylactic Effect ◽  
Moderate Dose ◽  
Metabolism Pathway ◽  
Dose Dependent

Abstract Vitamin D was empirically applied for Tuberculosis (TB) treatment in the past, and is currently used as an adjuvant for TB therapy. Although an increasing pile of evidences suggests that vitamin D has no therapeutic effect against TB infection, the prophylactic effect of vitamin D in preventing TB remains largely undetermined. To experimentally valuate the potential prophylactic effect of calcitriol (the active form of vitamin D) against mycobacterium infection, we performed dose-gradient calcitriol soaking in 30-day-old zebrafish before Mycobacterium marinum (M. marinum) challenge through tail vein injection. 1H-NMR metabolomics analysis was further performed for illustration of potential mechanisms underlying the prophylactic effect of calcitriol against M. marinum. The results suggested that calcitriol exerts dose-dependent prophylactic anti-mycobacterium effects, i.e., the bacterial load and the corresponding inflammatory factors (IL-1β, TNF-α, and IFN-γ) expressions in M. marinum challenged zebrafish were reduced by low-dose (25 µg/L) or high-dose (2500 µg/L) calcitriol soaking, rather than by moderate-dose (250 µg/L) calcitriol soaking. Body weight of the M. marinum challenged zebrafish was recovered by high-dose prophylactic calcitriol soaking rather than by low-dose or moderate-dose calcitriol. The 1H-NMR metabolomic profiling identified 29 metabolites with altered abundance among the dose-gradient calcitriol groups, among which 22 metabolites were co-varied with the dose of calcitriol, the rest 7 metabolites were co-varied with the bacterial load and the inflammatory response in term of cytokine expression. Further pathway analysis indicated that the glycine, serine, and threonine metabolism pathway was the activated in both of the two metabolite groups, indicating that the pathway was altered by dose-gradient of calcitriol and was in response to M. marinum infection in zebrafish. The results of the present study suggested that the activation of glycine, serine and threonine metabolism pathway may play a potential role for the dose-dependent anti-mycobacterium effect induced by prophylactic calcitriol soaking.

scholarly journals Intravenous administration of sodium propionate induces antidepressant or prodepressant effect in a dose dependent manner

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chunyan Hao ◽  
Zefeng Gao ◽  
XianJun Liu ◽  
Zhijiang Rong ◽  
Jingjing Jia ◽  
...  
Keyword(s):  
Body Weight ◽  
Low Dose ◽  
Antidepressant Effect ◽  
High Dose ◽  
Mild Stress ◽  
Dependent Manner ◽  
Reward Seeking ◽  
Metabolomic Profiling ◽  
Hydroxyanthranilic Acid ◽  
Dose Dependent

AbstractPropionate has been reported to exert antidepressant effects, but high-dose propionate may induce autism-like symptoms in experimental animals through induction of dysbiosis of neurotransmitters. The bi-directional effects of propionate seem to be dose-dependent. However, due to the pathological discrepancies between depression and autism, conclusions drawn from autism may not be simply transferable to depression. The effect and underlying action mechanisms of high-dose propionate on depression remains undetermined. To investigate the effects of propionate on depression, propionate dose gradients were intravenously administrated to rats exposed to chronic unpredictable mild stress (CUMS) for 1 week. Results of these behavioral tests demonstrate that low-dose propionate (2 mg/kg body weight/day) induces antidepressant effect through bodyweight recovery, elevated reward-seeking behaviors, and reduced depression-like behaviors, while high-dose propionate (200 mg/kg body weight/day) induces prodepressant effects opposite of those of low-dose propionate. A comprehensive profiling of neurotransmitters in the hippocampus demonstrated that CUMS induces reduction of NE (Norepinephrine), DA (Dopamine). GABA (γ-aminobutyric acid) was recovered by low-dose propionate, while high-dose propionate exerted more complicated effects on neurotransmitters, including reduction of NE, DA, 5-Hydroxytryptamine and Tryptophan, and increase of GABA, Kynurenine, Homovanillic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine. The neurotransmitters disturbed by high-dose propionate suggest metabolic disorders in the hippocampus, which were confirmed by the clear group separation in PCA of metabolomic profiling. The results of this study demonstrate the double-edged dose-dependent effects of propionate on depression and suggest potential cumulative toxicity of propionate as a food additive to mood disorders.

Successful Long Term Therapeutic Expression of Factor VIII in Hemophilia A Dogs After Administration of AAV-cFVIII Using a Two-Chain or Single Chain Delivery Approach.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 546-546
Author(s):  
Denise E. Sabatino ◽  
Ekaterina Altynova ◽  
Amy M. Lange ◽  
Shangzhen Zhou ◽  
Elizabeth P. Merricks ◽  
...  
Keyword(s):  
Low Dose ◽  
Hemophilia A ◽  
High Dose ◽  
Dependent Manner ◽  
Igg Antibodies ◽  
Single Chain ◽  
Spontaneous Bleeding ◽  
Aav Vector ◽  
Bleeding Episodes

Abstract Abstract 546 While adeno-associated virus (AAV) is a promising gene delivery vector, it has been challenging to deliver FVIII due to the large size of the FVIII cDNA and the high frequency of FVIII antibody formation in hemophilia A (HA) patients. We used two approaches to overcome the size limitation of AAV for FVIII: (1) two-chain delivery in which the canine FVIII (cFVIII) heavy chain (HC) is delivered in one AAV vector and the cFVIII light chain (LC) is delivered in a second AAV vector and (2) single chain delivery in which the B-domain deleted cFVIII cDNA with minimal regulatory elements is within one AAV vector. In the two-chain approach AAV-HC (4.0 Kb) and AAV-LC (3.9 Kb) with a liver specific promoter was co-injected at a dose of 6×1012 vector genomes/vector/kg or 1.25×1013vg/vector/kg using AAV8 or AAV9 via hepatic infusion. Five hemophilia A dogs treated with AAV-HC and AAV-LC expressed 0.5-11% cFVIII in a dose-dependent manner. The mean cFVIII activity based on Coatest assay for the low dose was 1.3% (>1220d)(Linus)(AAV8) and 0.6% (>1770d)(H19)(AAV9), while for the high dose it was 5.2% (800d)(F24)(AAV8) and 2.4% (>1270d)(Woodstock)(AAV9). One dog (J60) had a splenectomy due to a complication at the time of surgery and has maintained high levels of expression (mean 11.0%; >820d). The WBCT consistently remained at a mean of 17.6 min for low dose dogs and 13.7 min for high dose dogs compared to 8-12 min in normal dogs. Using novel reagents that we generated specific to cFVIII, we developed assays to detect cFVIII antigen levels and IgG antibodies. Despite receiving equal doses of each vector, at day 85 the cFVIII-LC antigen levels (71.7 ± 19.2 ng/ml) were >10-fold higher than would be predicted based on activity while the cFVIII-HC antigen levels (14.6 ± 9.2 ng/ml) were >3-fold higher than activity. Since functional FVIII synthesis relies on the co-transduction of AAV-HC and AAV-LC in the same cell, this suggests that only a portion of the vector co-transduces and expresses cFVIII in the same cell and that the light chain is secreted more efficiently than the HC. No IgG antibodies to cFVIII were detected at any time point in these dogs. Three dogs have maintained FVIII expression for >3.5 years and two dogs for >2 years with ongoing observation. No spontaneous bleeding episodes have been observed in these dogs for a cumulative observation of >16 years while >80 bleeding episodes would be expected during this time period. The second approach, the single chain delivery, overcomes the co-transduction requirement of the two-chain approach by ensuring that each transduced cell expresses functional FVIII. However, it is difficult to efficiently package the large 5.2 Kb single chain construct into an AAV vector. Since no significant differences were observed between AAV8 and AAV9 using the two-chain approach, we used AAV8 to deliver the single chain cFVIII by peripheral vein infusion at 2×1013vg/kg or 4×1013vg/kg. The mean cFVIII activity was 0.7% (>430d) for the low dose dog (L51) and 6.8% (>290d) and 2.2% (>110d) for the high dose dogs (M06, M50). cFVIII HC and LC ELISA showed that cFVIII antigen levels correlated with activity. WBCT was a mean of 19.1 min for L51, 15.3 min for M06 and 11.6 min for M50. No spontaneous bleeding episodes have been observed in these dogs. The high dose dogs had no IgG antibodies to FVIII. L51 had transient IgG antibodies to FVIII until d52 in the absence of a Bethesda titer. A rise in FVIII expression in L51 coincided with the disappearance of anti-cFVIII antibodies. Comparison of single chain and two-chain delivery of FVIII reveals that (1) long term therapeutic levels of cFVIII in a dose-dependent manner can be obtained with both delivery approaches; (2) circulating cFVIII antigen levels are >10-fold higher than activity in the two-chain delivery in contrast to single chain delivery in which antigen correlates with activity; and (3) high antigen levels may facilitate tolerance to FVIII in the setting of liver-directed gene transfer, since a transient non-inhibitory antibody was observed in only one dog with very low FVIII levels. Notably, no cellular toxicity due to continuous expression of various forms of FVIII was found in these animals based on long-term sustained FVIII expression levels and normal liver enzymes in all eight HA dogs. Further studies to characterize the immune responses to the transgene will define the optimal vector approach. These data will form the basis for clinical studies in humans with severe HA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Compound and Dose-Dependent Effects of Two Neonicotinoid Pesticides on Honey Bee (Apis mellifera) Metabolic Physiology

Insects ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 18 ◽  
Author(s):  
Steven C. Cook
Keyword(s):  
Honey Bee ◽  
Low Dose ◽  
Oral Exposure ◽  
High Dose ◽  
Dependent Manner ◽  
Bee Colony ◽  
Metabolic Physiology ◽  
Neonicotinoid Pesticides ◽  
Dose Dependent ◽  
Lethal Doses

Use of neonicotinoid pesticides is now ubiquitous, and consequently non-targeted arthropods are exposed to their residues at sub-lethal doses. Exposure to these neurotoxins may be a major contributor to poor honey bee colony health. Few studies have explored how sub lethal exposure to neonicotinoids affects honey bee metabolic physiology, including nutritional and energetic homeostasis, both of which are important for maintaining colony health. Reported here are results from a study of chronic oral exposure of honey bees to two sub lethal concentrations of clothianidin and imidacloprid. Neonicotinoids altered important aspects of honey bee nutritional and metabolic physiology in a compound and dose-dependent manner; both compounds at low doses reduced honey bee body weight. Low-dose clothianidin exposure resulted in bees having protein, lipids, carbohydrates, and glycogen levels similar to newly emerged bees. High-dose clothianidin exposure lowered lipids and glycogen content of bees. High-dose imidacloprid exposure resulted in bees having depressed metabolic rate. Low-dose imidacloprid exposure resulted in bees consuming low and high levels of protein and carbohydrate rich foods, respectively. Results suggest neonicotinoids interfere with honey bee endocrine neurophysiological pathways. Compound and dose-dependent effects might represent respective chemical structural differences determining an observed effect, and thresholds of compound effects on honey bee physiology.

Long Term Dose-Dependent Correction of Hemophilia A Dogs Using AAV-8 and AAV-9-Mediated FVIII Gene Transfer.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 999-999
Author(s):  
Denise E. Sabatino ◽  
Amy M. Lange ◽  
Melinda Mucci ◽  
Rita Sarkar ◽  
Aaron M. Dillow ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Dose Group ◽  
Low Dose ◽  
Hemophilia A ◽  
Clotting Factor ◽  
High Dose ◽  
Functional Assay ◽  
Dependent Manner ◽  
Aav Vector ◽  
Dose Dependent

Abstract Hemophilia A (HA) is an X-linked bleeding disorder characterized by deficiency in clotting factor VIII (FVIII). Current treatment for hemophilia is protein replacement therapy while a gene-based therapy would provide continuous expression of even low levels of FVIII protein (>1% of normal) that is likely to improve the disease phenotype. It is challenging to utilize an AAV-mediated gene transfer approach for the FVIII cDNA (4.4kb) since the AAV vector can only efficiently accommodate a <5.3kb transgene cassette. The FVIII protein is composed of 2 chains -the heavy chain (HC) and the light chain (LC). FVIII undergoes proteolytic cleavage and processing of the 2 individual chains that form the active FVIII protein. In other studies in HA dogs (n=8), no dose-response and AAV serotype-dependent FVIII expression has been documented, which illustrates the difficulties in using a FVIII single-chain approach. We have utilized a 2-chain approach in which the 2.4kb LC cDNA is packaged in one AAV vector while the 2.5kb HC is packaged into a second AAV vector. Each construct contains a 695bp thyroxine-binding globulin gene promoter/enhancer fused to a 175bp intron along with a 263bp SV40 poly A signal. For this approach the LC and HC vectors packaged into either AAV8 or AAV9 were administered to HA dogs via the hepatic artery. Two male HA dogs received HC and LC in AAV8 and 2 male dogs received HC and LC in AAV9 at doses of 6x1012gc/vector/kg (low dose) or 1.25x1013gc/v/kg (high dose). At 150 days after vector infusion, the high dose group expressed FVIII at levels of 4.8% (AAV8) and 3% (AAV9) as detected by a functional assay (Coatest assay). FVIII remained stable for 797 days (AAV8) and >200 days (AAV9) (the longest time points to date) without any evidence of antibody formation to the transgene. In the low dose group at 150 days, FVIII levels were 1.5% (AAV8) and 0.5% (AAV9) cFVIII activity and were maintained in a follow up period of >150 days (AAV8) and >700 days (AAV9) without formation of antibodies to FVIII. Thus, no major differences between AAV8 and AAV9 vectors were observed. The transgene product is also functional based on shortening of whole blood clotting time (baseline values >50 min), in a dose-dependent manner, 10–15 min and 16–20 min for the high and low dose cohorts, respectively. Interestingly, high dose injection of AAV8 to 2 female HA dogs (1.25x1013 and 3x1013gc/v/kg) results in FVIII levels of 1–2%, which is consistent with data obtained in mice on the poor performance of AAV in mediating gene transfer to liver in female animals. Liver function tests and other blood chemistries were transiently elevated after the surgical procedure and were in normal limits within 4 days. Importantly, all dogs did not develop antibodies to FVIII. These findings suggest that FVIII chains efficiently assemble in vivo without increasing the protein immunogenicity. The 4 male dogs have remained asymptomatic with no spontaneous bleeds, whereas >20 bleeding episodes were expected for this group since untreated dogs require 5.5 plasma infusions/year. These data demonstrate for the first time, dose-dependent sustained expression of functional cFVIII in HA dogs by AAV8 and AAV9 vectors without formation of antibodies to cFVIII.

scholarly journals Cardioprotective potential of polyphenols rich Thraatchathi Chooranam against isoproterenol induced myocardial necrosis in experimental rats

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ramakrishnan Ganapathy ◽  
Anita Ramachandran ◽  
Sushmitha Basavapattana Shivalingaiah ◽  
Muhammed Bishir ◽  
Saravanan Bhojaraj ◽  
...  
Keyword(s):  
Troponin I ◽  
Histopathological Examination ◽  
Antioxidant Properties ◽  
Membrane Integrity ◽  
Myocardial Necrosis ◽  
Experimental Period ◽  
High Dose ◽  
Dependent Manner ◽  
Protective Effects ◽  
Cardiac Tissues

Abstract Background The present study establishes the cardioprotective role of Thraatchathi Chooranam (TC), a polyherbal traditional Siddha medicine, in terms of membrane stabilizing and antioxidant properties in isoproterenol (ISO) induced myocardial necrosis model in rats. Methods Animals were divided into six groups (n = 6), normal (received vehicle 0.5% CMC, p.o.), ISO control (received 0.5% CMC + ISO 120 mg/kg, b.w. s.c. twice at an interval of 48 h), standard control (received Vit-E 100 mg/kg, p.o.) + ISO, TC low and high dose (50 and 100 mg/kg p.o., respectively) + ISO, and drug control (received TC at 100 mg/kg, p.o.). At the end of experimental period, blood samples collected and plasma cardiac troponin-I (CTn-I) was measured by ELISA. Cardiac tissues were isolated, levels of membrane stabilizing enzymes, antioxidants and inflammatory markers were estimated. Gene expression of Bax, Bcl2, Caspase 3, HIF-α, TNF-α, iNOS, TRX1 and TrxR were performed by RT-PCR. Histopathological studies on cardiac tissues were conducted using hematoxylin and eosin (H&E) stain. Statistical analyses were performed by one-way ANOVA followed by Tukey’s multiple comparison as post-hoc test. Results Administration of ISO resulted in a significant increase in plasma CTn-I, decrease in superoxide dismutase, glutathione and glutathione peroxidase; it also significantly altered membrane stabilizing enzymes like Na+/K+-ATPase, Mg2+-ATPase Ca2+-ATPase and Cathepsin D. Pretreatment with TC (50 mg/kg and 100 mg/kg) decreased CTn-I, and improved membrane stabilizing and endogenous antioxidant enzymes and decreased cathespin D level in a dose dependent manner. Histopathological examination revealed that TC improves cellular membrane integrity and decreases inflammatory cell infiltration and necrotic death. Conclusion The present study provided a strong evidence on the protective effects of TC against ISO-induced myocardial necrosis in rats.

scholarly journals Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abdelkader Hassani ◽  
Mohammad Mahdi Sabaghpour Azarian ◽  
Wisam Nabeel Ibrahim ◽  
Siti Aslina Hussain
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Gallic Acid ◽  
Cell Lines ◽  
Antioxidant Properties ◽  
Gum Arabic ◽  
Breast Adenocarcinoma ◽  
Therapeutic Effects ◽  
Dependent Manner

Abstract Gallic acid (GA) is a natural phenolic compound with therapeutic effects that are often challenged by its rapid metabolism and clearance. Therefore,  GA was encapsulated using gum arabic into nanoparticles to increase its bioavailability. The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. The GANPs were further evaluated for the in vitro cytotoxicity, cell uptake and cell migration in four types of human cancer cell lines including (MCF-7, MDA-MB231) breast adenocarcinoma, HepG2 hepatocellular cancer, HT-29 colorectal adenocarcinoma, and MCF-10A breast epithelial cell lines. The GANPs demonstrated potent antioxidant effects and have shown promising anti-cancer properties in a dose-dependent manner with a predilection toward HepG2 and MCF7 cancer cells. The uptake of GANPs was successful in the majority of cancer cells with a propensity to accumulate in the nuclear region of the cells. The HepG2 and MCF7 cancer cells also had a significantly higher percentage of apoptosis and were more sensitive to gallic acid nanoparticle treatment in the cell migration assay. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing  the antioxidant properties. The formulated nanoparticles also had remarkably low toxicity in normal cells. Based on these findings, GANPs may have promising therapeutic applications towards the development of more effective treatments with a probable targeting precision in cancer cells.

scholarly journals High-dose testosterone supplementation disturbs liver pro-oxidant/antioxidant balance and function in adolescent male Wistar rats undergoing moderate-intensity endurance training

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10228
Author(s):  
Ewa Sadowska-Krępa ◽  
Barbara Kłapcińska ◽  
Anna Nowara ◽  
Sławomir Jagsz ◽  
Izabela Szołtysek-Bołdys ◽  
...  
Keyword(s):  
Endurance Training ◽  
Low Dose ◽  
Thiobarbituric Acid ◽  
Adolescent Male ◽  
Moderate Intensity ◽  
High Dose ◽  
Anabolic Androgenic Steroid ◽  
Thiobarbituric Acid Reactive Substances ◽  
Androgenic Steroid ◽  
Male Wistar Rats

In some countries, anabolic-androgenic steroid abuse is rampant among adolescent boys and young men, including some of those seeking physical fitness and/or pleasing appearance through various exercise types. This tactic carries the risk of severe harmful health effects, including liver injury. Most anabolic-androgenic steroid stacking protocols employed are based on the use of the ‘prototypic’ anabolic-androgenic steroid testosterone and/or its esters. There is a vast body of data on the effects of anabolic-androgenic steroids’ abuse combined with physical exercise training on the liver antioxidant barrier in adult subjects, whereas those concerning adolescents are scant. This study aimed to assess, in adolescent male Wistar rats undergoing a 6-week moderate-intensity endurance training (treadmill running), the influence of concurrent weekly supplementation with intramuscular testosterone enanthate (TE, 8 or 80 mg/kg body weight/week) on selected indices of liver status and oxidative stress. The rats were sacrificed, and their livers and blood samples were harvested two days after the last training session. High-dose TE treatment significantly reduced body and liver weight gains. Neither low-dose nor high-dose TE treatment affected liver α-tocopherol or γ-tocopherol content, whereas low-dose TE treatment significantly lowered hepatic reduced glutathione content. TE treatment significantly elevated liver thiobarbituric acid-reactive substances content and blood activities of alkaline phosphatase and γ-glutamyltransferase, but not of aspartate aminotransferase or alanine aminotransferase. Liver catalase activity was lowered by >50% in both TE-treated groups, while superoxide dismutase activity was significantly but slightly affected (−15%) only by the high-dose TE treatment. Glutathione peroxidase and glutathione reductase activities were not significantly altered. TE treatment significantly increased liver thiobarbituric acid-reactive substances content and lowered blood HDL-cholesterol, but did not significantly affect LDL-cholesterol or triglycerides level. In conclusion, high-dose TE treatment significantly disturbed liver antioxidant barrier and prooxidative-antioxidative balance and hence counteracted favorable effects of concurrent moderate-intensity endurance training in adolescent male rats.

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