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Frontiers in Endocrinology 2023Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in... (Meta-Analysis)
Meta-Analysis
Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models.
BACKGROUND
Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility.
MATERIAL AND METHODS
We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen's d) and 95% confidence interval.
RESULTS
24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high-fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen's testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress.
CONCLUSIONS
Melatonin can reduce damage to male rodents' gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.
Topics: Animals; Male; Mice; Rats; Body Weight; Diabetes Mellitus; Hyperthyroidism; Infertility, Male; Melatonin; Metabolic Diseases; Obesity; Oxidative Stress; Rodentia; Semen; Testis
PubMed: 37476491
DOI: 10.3389/fendo.2023.1202560 -
Food Technology and Biotechnology Sep 2021The use of plants and their extracts in treatments of chronic diseases is widely known in traditional medicine. The aim of this study is to determine the effects of...
RESEARCH BACKGROUND
The use of plants and their extracts in treatments of chronic diseases is widely known in traditional medicine. The aim of this study is to determine the effects of 10-day consumption of blackthorn ( L.) flower extract on blood glucose, glycaemic load, serum α-amlyase activity and insulin concentration in normoglycaemic and hyperglycaemic (alloxan-induced) mice model.
EXPERIMENTAL APPROACH
Normoglycaemic and hyperglycaemic (treated with alloxan, 150 mg per kg body mass) C57BL/6 mice were administered daily, during 10 days, blackthorn flower extract by gavage. The sugar mass concentration within the extract was determined by HPLC analysis. In mice, blood and serum blood glucose concentrations, and oral glucose tolerance test were determined by blood glucometer. Serum insulin concentration was determined by ELISA assay and α-amylase activity by colourimetric assay.
RESULTS AND CONCLUSIONS
The blackthorn flower extract increased glucose concentrations in normoglycaemic mice by 30% after the 1st and 5th day and by 17% after the 10th day of consumption. It is a consequence of released sugars because sugar analysis revealed 59.8 mg/L monosaccharides, mainly fructose (55.7 mg/L) and glucose (24.3 mg/L) in the extract. On the contrary, the extract consumption reduced serum blood glucose in hyperglycaemic mice by 29% after 10 days of treatment. Oral glucose tolerance test also confirmed that in the hyperglycaemic group treated with blackthorn flower extract glucose homeostasis was improved and showed decrease in blood glucose. Serum insulin concentration increased by 49% and serum α-amylase activity by 46% after 10 days of treatment with blackthorn flower extract in hyperglycaemic group. Thus, it can be concluded that blackthorn flower extract improved glucose tolerance, enhanced insulin secretion and lowered serum α-amylase activity.
NOVELTY AND SCIENTIFIC CONTRIBUTION
The obtained results show for the first time the potential of blackthorn ( L.) flower extract in hyperglycaemia management.
PubMed: 34759766
DOI: 10.17113/ftb.59.03.21.7057 -
Frontiers in Pharmacology 2021Plants are well known in traditional herbal medicines for their hypoglycemic and hypolipidemic activities and are often used due to their accessibility, affordability,...
Plants are well known in traditional herbal medicines for their hypoglycemic and hypolipidemic activities and are often used due to their accessibility, affordability, and corollary effects. has been reported to control diabetes in folkloric medicine, but no known scientific research has been conducted to assess the plausibility of this assertion. Therefore, the current study is aimed to investigate the antidiabetic and hypolipidemic effects of leaves in alloxan-induced diabetic mice. The antidiabetic and antihyperlipidemic evaluation was conducted in Swiss albino mice at doses of 150-250°mg/kg for 15°days. The blood glucose, total cholesterol, triglyceride, LDL, HDL, creatinine, ALP, SGPT, and SGOT levels were estimated according to standard procedures. Phytochemicals of leaves were analyzed using GC-MS analysis. Enzymatic antioxidant activity of the plant was investigated spectrophotometrically by carrying out superoxide dismutase, peroxidase, and catalase assays. The membrane stabilization potential of leaf extracts was carried out using an haemolytic assay. The results revealed a dose response effect with the methanolic extract of which had significant antihyperglycemic effects at 150-250°mg/kg in alloxan treated mice, although less than the positive control (glibenclamide). Hyperlipidemic activity was significant at 250 mg/kg. The biochemical parameters, such as total cholesterol, triglyceride, LDL, HDL, creatinine, ALP, SGPT, and SGOT, were significantly improved ( < 0.01) by the methanolic extract of 250 mg/kg compared to the diabetic group. Treatment for 15 days showed significant elevation ( < 0.01) of antioxidant enzymes. GC-MS analysis provided tentative identifications of 52 compounds in the methanolic extract of of which 12 compounds have reported antidiabetic activity. In conclusion, methanolic extract of 150 and 250°mg/kg body weight showed significant antidiabetic and antihyperlipidemic activities in alloxan-induced diabetic mice and, with further work, has the potential to be used to manage blood glucose and cholesterol levels.
PubMed: 33897432
DOI: 10.3389/fphar.2021.643242 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: To evaluate morphological changes in long tubular bones of mature rats under the influence of experimental hyperglycemia.
OBJECTIVE
The aim: To evaluate morphological changes in long tubular bones of mature rats under the influence of experimental hyperglycemia.
PATIENTS AND METHODS
Materials and methods: The study was conducted on 140 nonlinear white male rats divided into two groups. The experimental group included rats that were introduced into a state of hyperglycemia by a single intraperitoneal injection of an alloxan dihydrate solution at a dose of 150 mg / kg body weight in 0.9% sodium chloride. The control group included rats that were injected with a similar volume of 0.9% sodium chloride one time intraperitoneally. The animals were taken out of the experiment on the 2nd, 30th, 60th, 90th, 120th, 150th and 180th day. Right and left femur and humerus were studied by morphometric and histological methods.
RESULTS
Results: Under conditions of prolonged uncontrolled hyperglycemia in mature rats, there is a slowdown in the growth rate of length and thickness of femur and humerus. This is indicated by a significant decrease in the length of bone and its diaphyses, as well as by a decrease in the cross-sectional area of the diaphysis, the width of the proximal and distal epiphyses, starting from 120 and 90 days of the experiment, respectively. The relative area of trabecular tissue, thickness of trabeculae and epiphyseal cartilage decreases in comparison with animals of the control group. The diameter of osteons and their channels increases in cortical tissue. Changes in the microarchitecture of the trabecular and cortical compartments of femur and humerus under conditions of hyperglycemia are similar and are characterized by a reduced bone mass, bone disorder progression and remodeling disorders.
CONCLUSION
Conclusions: Prolonged uncontrolled experimental hyperglycemia leads to slow growth of femur and humerus in mature rats, which is accompanied by an increase in microarchitecture disorder of the trabecular and cortical compartments, causing miniaturization of bones and, consequently, violation of their biomechanical properties and increased risk of fractures.
Topics: Animals; Bone Density; Bone and Bones; Femur; Fractures, Bone; Hyperglycemia; Male
PubMed: 34725275
DOI: No ID Found -
Oxidative Medicine and Cellular... 2019The addition of O-linked -N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins...
The addition of O-linked -N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT). Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood. Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy. OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux. In particular, we found that OGT knockdown increases the fusion between autophagosomes as well as lysosomes and stimulates autophagy to promote lysosomal-associated membrane protein 1 (LAMP-1). Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated. Together, our study reveals a mechanism by which the modulation of O-GlcNAcylation modification regulates autophagy in mouse cortical astrocytes.
Topics: Acetylglucosamine; Animals; Astrocytes; Autophagy; Cells, Cultured; Cerebral Cortex; Mice; Mice, Inbred ICR; N-Acetylglucosaminyltransferases; Phosphorylation; Protein Processing, Post-Translational; RNA, Small Interfering; Signal Transduction
PubMed: 31827688
DOI: 10.1155/2019/6279313 -
Life (Basel, Switzerland) Sep 2022belongs to the family Asteraceae, which has previously shown hepatoprotective, anticancer, and antioxidant activity. This study aimed to evaluate the antihyperglycemic...
belongs to the family Asteraceae, which has previously shown hepatoprotective, anticancer, and antioxidant activity. This study aimed to evaluate the antihyperglycemic and antihyperlipidemic activity of its root methanol extract and various fractions for the first time. This was performed using alloxan-induced diabetes in the rat model for both short, and long-term periods using different administration doses. Different biochemical parameters were studied and further consolidated by histopathological examination and in silico molecular modeling. The results showed that in the long-term study, at a dose of 400 mg/kg b.wt, the ethyl acetate fraction caused a pronounced reduction in fasting blood glucose level (FBG) and glycated hemoglobin (HbA) by 77.2% and 36.8%, respectively, compared to the diabetic group. This was confirmed by the histopathological examination of the animals' pancreatic sections. The ethyl acetate fraction also showed a reduction in total cholesterol (TC), total glycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels. It improved kidney and liver functions, causing a reduction in aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), urea, and creatinine levels. This is mainly attributed to its richness in secondary metabolites. Molecular docking showed that all the tested compounds showed certain inhibitory potential towards human α-glucosidase (HAG) and ATP citrate lyase (ACL). Thus, roots can help in the management of hyperglycemia, hyperlipidemia, and hepatic and kidney dysfunction.
PubMed: 36143486
DOI: 10.3390/life12091451 -
Foods (Basel, Switzerland) Feb 2023The current work was designed to evaluate the antioxidant activity and antidiabetic effect of L. extracts. For that, the leaves and buds of L. were analyzed to...
The current work was designed to evaluate the antioxidant activity and antidiabetic effect of L. extracts. For that, the leaves and buds of L. were analyzed to determine their polyphenolic and flavonoid contents and antioxidant activity. Diabetes was induced by a single dose of alloxan monohydrate (65 mg/kg body weight), then diabetic rats were treated with a dose of 200 mg/kg body weight of the methanolic extracts of leaves or buds or their combination for 30 days. Throughout the experiment, blood sugar and body weight were measured every 5 and 7 days respectively. At the end of the experiment, serum and urine were collected for analysis of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, creatinine, uric acid, urea, proteins, sodium, potassium, and chloride. Pancreas, liver, and kidney were removed to estimate catalase, glutathione peroxidase, and glutathione activities; lipid peroxidation products were also determined. The results obtained revealed that alloxan has induced hyperglycemia, increased liver and renal biomarkers levels, reduced antioxidative enzymes, and induced lipid peroxidation. However, the treatment with leaf and bud extracts, especially their combination, has attenuated all pharmacological perturbations induced by alloxan.
PubMed: 36832834
DOI: 10.3390/foods12040759 -
BMC Endocrine Disorders Oct 2022NADPH oxidase 1 (Nox1), which is highly expressed in the colon, is thought to play a potential role in host defense as a physical and innate immune barrier against...
BACKGROUND
NADPH oxidase 1 (Nox1), which is highly expressed in the colon, is thought to play a potential role in host defense as a physical and innate immune barrier against commensal or pathogenic microbes in the gastrointestinal epithelium. Diabetes can be caused by several biological factors, including insulin resistance is one of them. Alloxan is widely used to induce insulin-dependent diabetes in experimental animals. Alloxan increases the generation of reactive oxygen species as a result of metabolic reactions in the body, along with a massive increase in cytosolic calcium concentration.
METHODS
Using a universal method, a superoxide radical (О)-thermostable associate between NADPH-containing lipoprotein (NLP) and NADPH oxidase (Nox)- NLP-Nox was isolated and purified from the small intestine (SI) of control (C) and alloxan-induced diabetic (AD) albino rats.
RESULTS
In comparison to the C indices, in AD in the SI, an increase in the specific content of NLP-Nox associate and a decrease in the stationary concentration of produced О in liquid phase (in solution) and gas phase (during blowing by oxygen of the NLP-Nox solution) were observed. The NLP-Nox of SI associate in C and AD rats produced О by an immediate mechanism, using NLP as a substrate. The phenomenon of the hiding of the optical absorption maxima of the Nox in oxidized states at pH10,5 was observed in the composition of these SI associates of the C and AD rat groups. The characteristic absorption maxima of the «hidden» Nox were observed under these conditions after reduction by potassium dithionite.
CONCLUSION
Thus, at AD, the decrease in the stationary concentration of produced О in the solution and gas phase was compensated for by an increase in the specific amount of associate. In addition, the decrease in the stationary concentration of produced О by NLP-Nox associates at AD can be linked to a decrease in the level of NADPH in NLP-Nox composition. This could be used as a new mechanism of AD pathogenesis.
Topics: Animals; Alloxan; Calcium; Diabetes Mellitus, Experimental; Dithionite; Insulins; Intestine, Small; Lipoproteins; NADP; NADPH Oxidase 1; NADPH Oxidases; Oxygen; Potassium; Reactive Oxygen Species; Superoxides; Rats
PubMed: 36258207
DOI: 10.1186/s12902-022-01160-x -
Frontiers in Endocrinology 2021To investigate whether the microvascular permeability of lumbar marrow and bone trabecular changes in early-stage diabetic rabbits can be quantitatively evaluated using...
PURPOSE
To investigate whether the microvascular permeability of lumbar marrow and bone trabecular changes in early-stage diabetic rabbits can be quantitatively evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), quantitative computed tomography, and texture-analyzed permeability parameter map of DCE-MRI.
MATERIALS AND METHODS
This prospective study included 24 rabbits that were randomly assigned to diabetic (n = 14) and control (n = 10) groups. All rabbits underwent sagittal MRI of the lumbar region at 0, 4, 8, 12, and 16 weeks after alloxan injection. Pearson correlation coefficient was performed to determine the correlation between permeability parameter and bone mineral density (BMD). Repeated-measures ANOVA was used to analyze the changes in lumbar BMD over time in each group and the texture parameters of diabetic rabbit lumbar marrow at different time points. Mann-Whitney U rank sum test was used to compare the differences of each index between the two groups and calculate the area under the curve (AUC).
RESULTS
BMD was correlated with , , and but not with . At weeks 0-16, the BMD of the rabbits in the diabetic and normal groups was not statistically significant, but the change in BMD showed an overall downward trend. For texture analysis, entropy, energy, and Uniformized positive pixel (UPP) parameters extracted from the map showed significant differences from week 0 to 16 between the two groups. The identification ability at 8-12 weeks was higher than that at 12-16 weeks, and the AUCs were 0.734, 0.766, and 0.734, respectively (P < 0.05 for all).
CONCLUSIONS
The changes in BMD measured using quantitative computed tomography occurred later than those measured using bone trabecular morphometry. Texture analysis parameters based on DCE-MRI quantitative parameter Ktrans map are feasible to identify early changes in lumbar marrow structure in diabetic rabbits.
Topics: Alloxan; Animals; Bone Density; Bone Marrow; Cancellous Bone; Diabetes Mellitus, Experimental; Magnetic Resonance Imaging; Male; Prospective Studies; Rabbits; Tomography, X-Ray Computed
PubMed: 35002967
DOI: 10.3389/fendo.2021.785604 -
International Journal of Molecular... Sep 2022A series of heterocyclic compounds containing spirofused barbiturate and 3-azabicyclo[3.1.0]hexane frameworks have been studied as potential antitumor agents....
A series of heterocyclic compounds containing spirofused barbiturate and 3-azabicyclo[3.1.0]hexane frameworks have been studied as potential antitumor agents. Antiproliferative activity of products was screened in human erythroleukemia (K562), T lymphocyte (Jurkat), and cervical carcinoma (HeLa) as well as mouse colon carcinoma (CT26) and African green monkey kidney epithelial (Vero) cell lines. The most effective among the screened compounds show IC in the range from 4.2 to 24.1 μM for all tested cell lines. The screened compounds have demonstrated a significant effect of the distribution of HeLa and CT26 cells across the cell cycle stage, with accumulation of cells in SubG1 phase and induced apoptosis. It was found, using a confocal microscopy, that actin filaments disappeared and granular actin was distributed diffusely in the cytoplasm of up to 90% of HeLa cells and up to 64% of CT26 cells after treatment with tested 3-azaspiro[bicyclo [3.1.0]hexane-2,5'-pyrimidines]. We discovered that the number of HeLa cells with filopodium-like membrane protrusions was reduced significantly (from 91% in control cells to 35%) after treatment with the most active compounds. A decrease in cell motility was also noticed. Preliminary in vivo experiments on the impact of the studied compounds on the dynamics of CT26 tumor growth in Balb/C mice were also performed.
Topics: Actins; Animals; Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Chlorocebus aethiops; Drug Screening Assays, Antitumor; HeLa Cells; Hexanes; Humans; Mice; Pyrimidines
PubMed: 36142688
DOI: 10.3390/ijms231810759