Evaluating the histomorphological and biochemical changes induced by Tributyltin Chloride on pituitary-testicular axis of adult albino rats and the possible ameliorative role of hesperidin.

This study was performed to explore in detail the toxic effects of Tributyltin Chloride (TBT) on the pituitary-testicular axis and the possible amelioration with Hesperidin. Seventy-two adult male albino rats were divided into four groups: Control group (I), TBT-treated group (II), TBT+Hesperidin group (III), and Recovery group (IV). Body and testicular weights were measured. Blood samples were taken to estimate serum levels of testosterone, FSH and LH hormones by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) level was measured in testes homogenates. Tissue samples from the pituitary glands and testes were processed for light, electron microscope examination, and immunohistochemical detection of anti-FSH, and Ki67 proteins. Results showed a statistically significant decrease in testicular weight, serum testosterone, FSH and LH levels and a significant increase in tissue MDA in the TBT group when compared to the control group. TBT treatment caused severe histopathological changes with decreased area percent of PAS-stained basophils, and anti FSH immuno-stained gonadotrophs in the pituitary gland. The testes of group II also showed marked tissue damage, cell loss with decreased epithelial height and decreased number of proliferating spermatogenic cells. Hesperidin supplementation with TBT proved significant amelioration of the previously mentioned parameters in both glands which could improve male fertility. In conclusion: The flavonoid Hesperidin has the potential to protect against the reproductive damage induced by TBT in susceptible individuals.

Histological and biochemical evaluation of the effects of silver nanoparticles (AgNps) versus titanium dioxide nanoparticles (TiO2NPs) on rat parotid gland.

The unlimited use of nanoparticles (NPs) results in toxic impacts on different tissues. The current study aimed to compare the adverse effects of AgNPs and TiO2NPs on the parotid gland of adult male albino rats as regards the histopathological, immunohistochemical, and biochemical changes, exploring the possible underlying mechanisms and the degree of improvement after cessation of administration. Fifty-four adult male albino rats were divided into control group (I), AgNPs-injected group (II), and TiO2NPs-injected group (III). We measured the levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) in the serum, and levels of MDA and GSH in parotid tissue homogenate. Quantitative real-time polymerase-chain reaction (qRT-PCR) was used to measure the expression levels of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1-α), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), mouse double minute 2 (MDM2), Caspase-3 Col1a1, and Occludin. Parotid tissue sections were examined by light microscope (Hematoxylin & Eosin and Mallory trichrome stains), electron microscope, and immunohistochemical examination of CD68 and anti-caspase-3 antibodies. Both NPs severely affected the acinar cells and damaged the tight junction between them by enhancing expression of the inflammatory cytokines, inducing oxidative stress, and disturbing the expression levels of the studied genes. They also stimulated fibrosis, acinar cell apoptosis, and inflammatory cells infiltration in parotid tissue. TiO2NPs effects were less severe than AgNPs. Cessation of exposure to both NPs, ameliorated the biochemical and structural findings with more improvement in TiO2NPs withdrawal. In conclusion: AgNPs and TiO2NPs adversely affected the parotid gland, but TiO2NPs were less toxic than AgNPs.

Hypoxia pretreatment enhances the therapeutic potential of mesenchymal stem cells (BMSCs) on ozone-induced lung injury in rats.

Ozone (O3) gas is a double-sided weapon. It provides a shield that protects life on earth from the harmful ultraviolet (UV) rays, but ground-level O3 is considered an urban air pollutant. So, a rat model of chronic O3 inhalation was established to assess the biochemical and morphological alterations in the lung tissue and to investigate the ameliorative effects of bone marrow-derived mesenchymal stem cells (BMSCs) with or without hypoxia pre-treatment. Forty-two adult male albino rats were divided into four groups: control, ozone-exposed, normoxic BMSC-treated, and hypoxic BMSC-treated groups. Lung tissue sections were processed for light and electron microscope examination, immunohistochemical staining for caspase 3, and iNOS. Quantitative real-time PCR for IL-1α, IL-17, TNF-α, and Nrf2 mRNA gene expression were also performed. Chronic O3 exposure caused elevated inflammatory cytokines and decreased antioxidant Nrf2 mRNA expression. Marked morphological alterations with increased collagen deposition and elevated apoptotic markers and iNOS were evident. BMSC treatment showed immunomodulatory (decreased inflammatory cytokine gene expression), antioxidant (increased Nrf2 expression and decreased iNOS), and anti-apoptotic (decreased caspase3 expression) effects. Consequently, ameliorated lung morphology with diminished collagen deposition was observed. Hypoxia pretreatment enhanced BMSC survival by MTT assay. It also augmented the previously mentioned effects of BMSCs on the lung tissue as proved by statistical analysis. Lung morphology was similar to that of control group. In conclusion, hypoxia pretreatment represents a valuable intervention to enhance the effects of MSCs on chronic lung injury.

Histomorphological changes and molecular mechanisms underlying the ameliorative effect of resveratrol on the liver of silver nanoparticles-exposed rats.

Exposure to the deleterious effects of silver nanoparticles (AgNPs) is inevitable due to their wide use in medicine and daily life. The current study aimed to delineate the histomorphological changes and the molecular mechanisms underlying the ameliorative effect of Resveratrol (RSV) on rats' livers exposed to AgNPs. Fifty healthy adult male Wistar albino rats were divided into four groups: control, AgNPs-exposed, RSV-treated after AgNPs exposure, and recovery groups. Liver sections were examined by light and electron microscopes, and immunohistochemistry was performed for detection of activated caspase3 and TNFα. Serum ALT and AST, plasma levels of TNFα, IL-6, GSH and SOD were measured. mRNA expression of SIRT1, ADORA3, PAI, CDK1, Nrf2 and NFκB genes in liver tissue homogenate was performed using qRT-PCR. AgNPs-exposure for 28 days caused marked liver tissue damage with trapping in hepatocytes and Kupffer cells, while RSV treatment ameliorated liver ultrastructure and function. Our results clarified the molecular basis of RSV ameliorative effect on liver tissue by significant upregulation of SIRT1-NrF2 signaling pathway with increased levels of the antioxidant GSH and SOD, which represent the antioxidant effect of RSV. Significant upregulation of the protective ADORA3 with downregulation of the proinflammatory PAI-1 and NFκB mRNA expression levels besides decreased plasma levels of TNFα, IL-6 and decreased immunoexpression of TNFα in liver tissue, represent the anti-inflammatory effect of RSV. In addition, decreased immunoexpression of caspase3 and downregulation of CDK1 expression, represent its antiapoptotic effect. In conclusion: RSV ameliorates AgNPs-induced liver damage by antioxidant, anti-inflammatory and antiapoptotic effects.Abbreviations: AgNPs: Silver nanoparticles, RSV: Resveratrol, ROS: Reactive oxygen species, ESR: Electron spin resonance, DMPO: 5,5-Dimethyl-1-pyrroline-N-oxide, H2O2: Hydrogen peroxide, SOD: Superoxide dismutase, CAT: Catalase, GPx: Glutathione peroxidase, MPTP: Methyl-4-phenyl-1.2.3.6-tetrahydropyridine, MDA: Malondialdehyde, TNF: Tumor necrosis factor, GSH: Glutathione, Nrf2: Nuclear factor-erythroid 2-related factor 2, ARE: Antioxidant response elements, KEAP1: Kelch-1ike ECH-associated protein l, AMPK: AMP-activated protein kinase, HO-1: Heme oxygenase-1, NF-κB: Nuclear factor-kappa B, SIRT1: Sirtuins, FOXO: Forkhead box, UCP2: Uncoupling protein 2, STZ: Streptozotocin nicotinamide, HSC: hepatic stellate cells, ECM: extracellular matrix.

The possible protective role of zinc oxide nanoparticles (ZnONPs) on testicular and epididymal structure and sperm parameters in nicotine-treated adult rats (a histological and biochemical study).

Exposure to nicotine in smoking contributes to most unexplained male infertility but the mechanisms remain to be fully elucidated. Zinc (Zn) is an essential trace element in normal growth, development and reproduction. Zinc oxide nanoparticles (ZnONPs) are well-known antioxidants. Therefore, this work was designed to investigate the potential ability of ZnONPs to protect testis and epididymis in nicotine-treated rats. Forty adult male Wistar albino rats were divided into control group and two experimental groups (treated and supplemented rats). In the treated group, rats received nicotine at a dose of 1 mg/kg/day orally for 30 days. Rats in the supplemented group received ZnONPs (10 mg/kg/day) with nicotine (1 mg/kg/day), orally for the same period. Testicular and epididymal sections were stained with H&E to assess the histological changes. Negrosin-eosin staining of epididymal sperms was performed to assess their viability and morphological changes. Serum testosterone, FSH and LH levels were assessed. Also, oxidative stress parameters and semiquantitative real-time PCR for steroidogenic enzymes were measured. Morphometric studies of both organs were statistically analyzed. Mild to severe testicular and epididymal structural changes together with sperm morphological abnormalities were detected in nicotine-treated rats. Biochemical results also showed a decrease in all measured parameters except for an increased malondialdehyde (MDA) level that meant deterioration of their reproductive function. On the other hand, ZnONP supplementation in the last group showed an obvious improvement in all investigated parameters.

Fluoxetine pretreatment enhances neurogenic, angiogenic and immunomodulatory effects of MSCs on experimentally induced diabetic neuropathy.

Being one of the most debilitating complications among diabetic patients, diabetic polyneuropathy (DPN) is a paramount point of continuous research. Stem cell therapies have shown promising results. However, limited cell survival and paracrine activities hinder its transfer from bench to bedside. We designed this study to evaluate fluoxetine-pretreatment technique of mesenchymal stem cells (MSCs) as an approach to enhance their paracrine and immunomodulatory properties in DPN. Effects of fluoxetine treatment of MSCs were tested in vitro. Forty-two adult Wistar male albino rats were utilized, further subdivided into control, diabetic, MSC-treated and fluoxetine-pretreated MSC groups. Sciatic nerve sections were prepared for light and electron microscope examination and immunohistochemical detection of neurofilament (NF) protein. Also, we assessed in vitro survival and paracrine properties of fluoxetine-pretreated MSCs. Real time PCR of BDNF, VEGF, IL-1ß, and IL-10 expression in tissue homogenate was performed. Our results showed restoration of normal neuronal histomorphology and ultrastructure, moreover, immunohistochemical expression of anti-neurofilament protein was significantly elevated in MSC-treated groups compared to the diabetic one. Fluoxetine enhanced the MSC survival and their paracrine properties of MSCs in vitro. Furthermore, the fluoxetine-pretreated MSC group revealed a significant elevation of mRNA expression of BDNF (neurotrophic factor) and VEGF (angiogenic factor), denoting ameliorated MSC paracrine properties. Similarly, improved immunomodulatory functions were evident by a significant reduction of interleukin-1ß mRNA expression (pro-inflammatory) and a reciprocal significant increase of interleukin-10 (anti-inflammatory). We concluded that fluoxetine-pretreatment of MSCs boosts their survival, paracrine, and immunomodulatory traits and directly influenced neuronal histomorphology. Hence, it presents a promising intervention of diabetic polyneuropathy. Graphical Abstract.

Effect of human umbilical cord blood mesenchymal stem cells administered by intravenous or intravitreal routes on cryo-induced retinal injury.

Traumatic optic neuropathy is an important cause of severe vision loss. So, many attempts were performed to transplant stem cells systemically or locally to regenerate the injured retina. In this study, we investigated the effect of human umbilical cord blood mesenchymal stem cells (hUBMSCs) on histological structure, apoptotic, antiapoptotic, oxidant and antioxidant markers in an experimental model of cryo-induced retinal damage in mice. Forty-eight mice were included with 4 major groups; group I contained 18 mice as controls. The others included 30 mice exposed to cryo-induced retinal injury and were subdivided into three equal groups: group II received no treatment after injury. Group III was intravenously injected with hUCBMSCs after injury and group IV received an intravitreal injection with hUCBMSCs into both eyes. Retinal tissues were used for histopathological, immunological and gene expression studies. Real time-PCR was performed to assess B-cell lymphoma 2 (bcl2), Bcl2-associated X protein (bax), heme oxygenase-1 (hmox-1) and thioredoxin-2 (tnx-2) expression and to assess the differentiation of the stem cells into the retinal tissue. Immunohistochemical analysis was performed to assess caspase-3, 3-nitrotyrosine (3-NT) and basic fibroblast growth factor (bFGF). Disturbed retinal structure was seen in cryo-injured mice while hUCBMSCs treated groups showed nearly normal structure. By real time-PCR, significantly reduced mRNA expressions of Bax and notably enhanced mRNA expression of Bcl-2, hmox-1 and txn-2 were demonstrated in retinal injured mice with hUCBMSCs treatment compared to those without. In addition, immunohistochemical analysis confirmed downregulation of 3-NT and caspase-3 and upregulation of bFGF after hUCBMSCs injection in injured retina. Furthermore, there was no differentiation of transplanted stem cells into the retinal tissue. In conclusions, hUCBMSCs could improve the morphological retinal structure in cryo-induced retinal damage model by modulation of the oxidant-apoptotic status and by increased the expression of bFGF. © 2017 IUBMB Life, 69(3):188-201, 2017.

Granulocyte-colony stimulating factor ameliorates di-ethylhexyl phthalate-induced cardiac muscle injury via stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms.

Phthalates are common plasticizers present in medical-grade plastics and other everyday products. Di-ethylhexyl phthalate (DEHP) has been noted as a causative risk factor for the initiation and augmentation of cardiovascular functional disorders. G-CSF is a glycoprotein found in numerous tissues throughout the body and is currently applied in clinical practice and has been tested in congestive heart failure. We aimed to examine in depth the effect of DEHP on the histological and biochemical structure of the cardiac muscle in adult male albino rats and the mechanisms underlying the possible ameliorative effect of G-CSF. Forty-eight adult male albino rats were divided into control group, DEHP group, DEHP+ G-CSF group and DEHP-recovery group. We measured serum levels of aspartate aminotransferase (AST), creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Left ventricular sections were processed for light and electron microscope examination, and immunohistochemical staining of Desmin, activated Caspase-3 and CD34. DEHP significantly increased enzyme levels, markedly distorted the normal architecture of cardiac muscle fibers, downregulated Desmin protein levels and enhanced fibrosis, and apoptosis. G-CSF treatment significantly decreased the enzyme levels compared to DEHP group. It enhanced CD34 positive stem cells recruitment to injured cardiac muscle, therefore improved the ultrastructural features of most cardiac muscle fibers via anti-fibrotic and anti-apoptotic effects in addition to increased Desmin protein expression levels. The recovery group showed partial improvement due to persistent DEHP effect. In conclusion, administration of G-CSF effectively corrected the histopathological, immunohistochemical and biochemical alterations in the cardiac muscle after DEHP administration by stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms.

Combined Bazedoxifene and Genistein Ameliorate Ovariectomy-Induced Hippocampal Neuro-Alterations via Activating CREB/BDNF/TrkB Signaling Pathway.

OBJECTIVES: The scientific research community devotes stupendous efforts to control the arguable counterbalance between the undesirable effects of hormone replacement therapy (HRT) and post-menopausal syndrome. The recent emergence of 3rd generation selective estrogen receptor modulators and phytoestrogens has provided a promising alternative to HRT. Hence, we assessed the potential effects of combined Bazedoxifene and Genistein on hippocampal neuro-alterations induced by experimental ovariectomy. METHODS: For this purpose, we utilized forty-eight healthy sexually mature female Wistar rats assorted to control, ovariectomy (OVX), Genistein-treated ovariectomized (OVX+GEN) and Bazedoxifene and Genistein-treated ovariectomized (OVX+BZA+GEN) groups. Hippocampi samples from various groups were examined by H&E, silver stains and immunohistochemical examination for calbindin-D28k, GFAP, and BAX proteins. We also assessed hippocampal mRNA expression of ERK, CREB, BDNF and TrkB. RESULTS: Our histopathological results confirmed that combined BZA+GEN induced restoration of hippocampal neuronal architecture, significant reduction of GFAP and BAX mean area % and significant upregulation of calbindin-D28k immunoexpression. Furthermore, we observed significant upregulation of ERK, CREB, BDNF and TrkB mRNA expression in the BZA+GEN group compared to the OVX group. CONCLUSION: Taken together, our findings have provided a comprehensive assessment of histological, immunohistochemical and cyto-molecular basis of combined Genistein and Bazedoxifene ameliorative impacts on hippocampal neuro-alterations of OVX rats via upregulation of Calbindin, CERB, BDNF, Trk-B and ERK neuronal expression.

Electric field-directed migration of mesenchymal stem cells enhances their therapeutic potential on cisplatin-induced acute nephrotoxicity in rats.

Cisplatin is widely used as an anti-neoplastic agent but is limited by its nephrotoxicity. The use of mesenchymal stem cells (MSCs) for the management of acute kidney injury (AKI) represents a new era in treatment but effective homing of administered cells is needed. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on cisplatin-induced AKI in rats after directed migration by electric field (EF). Forty-eight adult male albino rats were equally classified into four groups: control, cisplatin-treated, cisplatin plus BM-MSCs, and cisplatin plus BM-MSCs exposed to EF. Serum levels of IL-10 and TNF-α were measured by ELISA. Quantitative real-time PCR analysis for gene expression of Bcl2, Bax, caspase-3, and caspase-8 was measured. Hematoxylin and eosin (H&E) staining, periodic acid Schiff staining, and immunohistochemical analysis were also done. MSC-treated groups showed improvement of kidney function; increased serum levels of IL-10 and decreased levels of TNF-α; and increased mRNA expression of Bcl2 and decreased expression of Bax, caspase-3, and caspase-8 proteins comparable to the cisplatin-injured group. EF application increased MSCs homing with significant decrease in serum urea level and caspase-3 gene expression together with significant increase in Bcl2 expression than occurred in the MSCs group. Restoration of normal kidney histomorphology with significant decrease in immunohistochemical expression of caspase-3 protein was observed in the BM-MSCs plus EF group compared to the BM-MSCs group. EF stimulation enhanced the MSCs homing and improved their therapeutic potential on acute cisplatin nephrotoxicity.

Neuroprotective effects of quercetin on the cerebellum of zinc oxide nanoparticles (ZnoNps)-exposed rats.

Engineered nanomaterials induce hazardous effects at the cellular and molecular levels. We investigated different mechanisms underlying the neurotoxic potential of zinc oxide nanoparticles (ZnONPs) on cerebellar tissue and clarified the ameliorative role of Quercetin supplementation. Forty adult male albino rats were divided into control group (I), ZnONPs-exposed group (II), and ZnONPs and Quercetin group (III). Oxidative stress biomarkers (MDA & TOS), antioxidant biomarkers (SOD, GSH, GR, and TAC), serum interleukins (IL-1ß, IL-6, IL-8), and tumor necrosis factor alpha (TNF-α) were measured. Serum micro-RNA (miRNA): miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-3p expression levels were quantified by real-time quantitative polymerase-chain reaction (RT-QPCR). Cerebellar tissue sections were stained with Hematoxylin & Eosin and Silver stains and examined microscopically. Expression levels of Calbindin D28k, GFAP, and BAX proteins in cerebellar tissue were detected by immunohistochemistry. Quercetin supplementation lowered oxidative stress biomarkers levels and ameliorated the antioxidant parameters that were decreased by ZnONPs. No significant differences in GR activity were detected between the study groups. ZnONPs significantly increased serum IL-1ß, IL-6, IL-8, and TNF-α which were improved with Quercetin. Serum miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-p expression levels showed significant increase in ZnONPs group, while no significant difference was observed between Quercetin-treated group and control group. ZnONPs markedly impaired cerebellar tissue structure with decreased levels of calbindin D28k, increased BAX and GFAP expression. Quercetin supplementation ameliorated cerebellar tissue apoptosis, gliosis and improved calbindin levels. In conclusion: Quercetin supplementation ameliorated cerebellar neurotoxicity induced by ZnONPs at cellular and molecular basis by different studied mechanisms.Abbreviations: NPs: Nanoparticles, ROS: reactive oxygen species, ZnONPs: Zinc oxide nanoparticles, AgNPs: silver nanoparticles, BBB: blood-brain barrier, ncRNAs: Non-coding RNAs, miRNA: Micro RNA, DMSO: Dimethyl sulfoxide, LPO: lipid peroxidation, MDA: malondialdehyde, TBA: thiobarbituric acid, TOS: total oxidative status, ELISA: enzyme-linked immunosorbent assay, H2O2: hydrogen peroxide, SOD: superoxide dismutase, GR: glutathione reductase, TAC: total antioxidant capacity, IL-1: interleukin-1, TNF: tumor necrosis factor alpha, cDNA: complementary DNA, RT-QPCR: Real-time quantitative polymerase-chain reaction, ABC: Avidin biotin complex technique, DAB: 3', 3-diaminobenzidine, SPSS: Statistical Package for Social Sciences, ANOVA: One way analysis of variance, Tukey's HSD: Tukey's Honestly Significant Difference, GFAP: glial fiberillar acitic protein, iNOS: Inducible nitric oxide synthase, NO: nitric oxide, HO-1: heme oxygenase-1, Nrf2: nuclear factor erythroid 2-related factor 2, NF-B: nuclear factor-B, SCI: spinal cord injury, CB: Calbindin.

Rapamycin-filgrastim combination therapy ameliorates portal hypertension-induced splenomegaly: Role of ß actin and S100A9 proteins modulation.

Objectives: Thioacetamide (TAA) was administered to induce an animal model of liver disease with secondary splenomegaly to assess the mechanisms underlying the effects of rapamycin and filgrastim when taken separately or in combination on the biochemical and histopathological aspects of the liver and spleen. Materials and Methods: Thirty adult male albino rats were divided into five groups (control, TAA-treated group, TAA+rapamycin, TAA+filgrastim, and TAA+rapamycin+filgrastim group). We measured relative liver and spleen weights, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin. Molecular docking modeling and histopathological examination of liver and spleen sections with hematoxylin and eosin and Masson trichrome staining with immunohistochemical detection of splenic CD3 and CD20 lymphocytes, S100A9 and ß actin antibodies were detected. Morphometric and statistical analyses of the results were performed. Results: TAA administration altered the histological structure of the liver and spleen and impaired liver function. It increased the expression of splenic CD3, CD20 lymphocytes, and S100A9 while diminishing the expression of ß actin. Each of rapamycin and filgrastim, when administered separately, improved liver and spleen indices and liver function, but rapamycin did not affect the albumin level. They lowered splenic B and T lymphocyte levels. Expression levels of S100A9 showed down-regulation while ß actin levels were up-regulated when compared with TAA. Combination therapy improved liver and spleen tissue pathology and significantly ameliorated the expression of splenic lymphocytes through regulation of S100A9 and ß actin expression. Conclusion: The synergistic effect of combination therapy was dependent on the regulation of splenic S100A9 and ß actin levels.

Effects of Quercetin and Coenzyme Q10 on Biochemical, Molecular, and Morphological Parameters of Skeletal Muscle in Trained Diabetic Rats.

BACKGROUND: Diabetes mellitus (DM) affects the musculoskeletal system through its metabolic perturbations. Exercise modulates blood sugar levels and increases the body's sensitivity to insulin in patients with DM. OBJECTIVE: This study aimed to investigate the potential effects of combined quercetin and coenzyme Q10 (CoQ10) supplements with or without exercise on the histological, biochemical and molecular structures of diabetic rat's skeletal muscle Methods: A total of 64 adult male albino rats were divided into six groups: control, trained nondiabetic, non-trained diabetic, diabetic rats treated with combined CoQ10 and quercetin, diabetic rats with treadmill training, and diabetic rats treated with treadmill training and CoQ10 and quercetin. Blood and skeletal muscle samples were obtained from all groups for routine histological examination and biochemical determination of cytokine levels and protein activities. Quantitative real-time polymerase chain reaction (qRT-PCR) and morphometric analysis of PAS and Bax expressions were also performed. RESULTS: Biochemical analysis revealed improvement in all studied parameters with combined Co- Q10 and quercetin than exercise training alone. Combined treatment and exercise showed significant improvement in all parameters especially interleukin 6 and malondialdehyde. Fibronectin type III domain-containing protein 5 (FNDC5) expression and irisin levels increased in all trained groups but combined treatment with exercise significantly increased their levels than exercise alone. Histological analysis revealed improvement after exercise or combined treatment; however, when exercise was combined with CoQ10 and quercetin, marked improvement was observed. CONCLUSION: the combination of CoQ10 and quercetin could be promising in preserving musculoskeletal function in patients with DM concomitantly with physical exercise.

Evaluating the effect of silver nanoparticles on testes of adult albino rats (histological, immunohistochemical and biochemical study).

Silver nanoparticles (AgNPs) are widely used in medicine, however, they have toxic impacts on different organs. AgNPs distribution to the testes was reported, so, we aimed to study the effect of intraperitoneal injection of AgNPs, at different concentrations and different time durations, on adult rat testes. Sixty healthy adult male Wistar albino rats were divided into three groups; control group (Group I) and two experimental groups (Groups II & III), each of which were subdivided into two subgroups. Rats in group II were exposed for 7 days to low and high doses of AgNPs, respectively. Rats in group III were exposed for 28 days to low and high doses of AgNPs, respectively. Testicular sections were stained with H&E, Toluidine blue, Immunohistochemical staining for Ki-67 and CD68 and Electron microscope examination were performed. Serum testosterone level and Quantitative Real-Time PCR for spermatogenesis genes were measured. Group IIa & IIb showed thickened capsule studded with nanoparticles, congested blood vessels, disorganized seminiferous tubules (Sts) and detached germinal epithelium. Group IIIa & IIIb showed marked reduction in the germinal epithelium, and shrunken Sts with the absence of sperms in most of them, which was more evident with higher doses of AgNPs. Significant decrease in cell proliferation and increase in interstitial tissue macrophages were more detected in groups II & III than in the control group. Decreased serum testosterone and decreased expression levels of spermatogenesis genes in groups IIa, IIb & IIIa, IIIb than in the control group were observed. IN CONCLUSION: intraperitoneal injection of AgNPs adversely affected the structure of adult rat testes. The tissue damage was more manifested with increased dose and duration of exposure.

Morphological alterations in the jejunal mucosa of aged rats and the possible protective role of green tea.

INTRODUCTION: Gastrointestinal disorders become more prevalent with ageing. This study is aimed to describe morphological changes that occur in the jejunal mucosa of male albino rats as a result of ageing and the protec-tive effect of green tea (GT) extract. MATERIAL AND METHODS: The experiment was performed on sixty rats: thirty young-adult (6-month old, body mass 200-220 g) and thirty old (24-month-old, body mass 220-260 g) animals. Each group was further divided into two subgroups (n = 15 each): control rats and GT-treated rats that received 1.5 mL (300 mg/kg/day) of GT extract for 14 weeks by oral gavage. Sections of the jejunum were stained with hematoxylin and eosin, periodic acid Schiff, toluidine blue and Mallory trichrome methods. The presence of proliferating cell nuclear antigen (PCNA)- and CD68-positive cells was evaluated by immunohistochemical staining. Ultrathin sections were prepared and examined by a transmission electron microscope (TEM). RESULTS: Jejunal sections of the old control rats showed distortion of submucosa and attenuated muscularis externa with decreased height of intestinal villi. The villi also showed partial loss of acidophilic brush border with wide spaces between enterocytes. Swollen, short, blunt or broad villi with abundant mononuclear cell infiltration of lamina propria and congested blood vessels were evident both by light and electron microscopy. The number of PCNA- and CD68-positive cells in jejunal mucosa of old rats was higher than in young rats. The activity of glutathione peroxidase (GPX) and total antioxidant capacity (TAC) in the mucosa of old control rats were lower, whereas malondialdehyde (MDA) levels were higher in the jejunal homogenates of old rats as compared to young control rats. Administration of GT extract protected the jejunal mucosa from age-related changes by restoring its histological structure. The treatment of old rats with GT extract significantly decreased MDA levels in the jejunum and increased TAC and GPX activity. CONCLUSIONS: The age-related changes of the morphology of rat jejunum could be ameliorated by prolonged supplementation of the green tea extract.