Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

BACKGROUND: Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. OBJECTIVES: The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. METHODS: Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. RESULTS: BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. CONCLUSION: The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Alleviation of doxorubicin-induced cardiotoxicity in rat by mesenchymal stem cells and olive leaf extract via MAPK/ TNF-α pathway: Preclinical, experimental and bioinformatics enrichment study.

BACKGROUND: Toxic cardiomyopathies were a potentially fatal adverse effect of anthracycline therapy. AIM: This study was conducted to demonstrate the pathogenetic, morphologic, and toxicologic effects of doxorubicin on the heart and to investigate how the MAPK /TNF-α pathway can be modulated to improve doxorubicin-Induced cardiac lesions using bone marrow-derived mesenchymal stem cells (BM-MSCs) and olive leaf extract (OLE). METHODS: During the study, 40 adult male rats were used. Ten were used to donate MSCs, and the other 30 were split into 5 equal groups: Group I was the negative control, Group II obtained oral OLE, Group III obtained an intraperitoneal cumulative dose of DOX (12 mg/kg) in 6 equal doses of 2 mg/kg every 48 h for 12 days, Group IV obtained intraperitoneal DOX and oral OLE at the same time, and Group V obtained intraperitoneal DOX and BM-MSCs through the tail vein at the same time for 12 days. Four weeks after their last dose of DOX, the rats were euthanized. By checking the bioinformatic databases, a molecularly targeted path was selected. Then the histological, immunohistochemistry, and gene expression of ERK, JNK, NF-κB, IL-6, and TNF-α were done. RESULTS: Myocardial immunohistochemistry revealed severe fibrosis, cell degeneration, increased vimentin, and decreased CD-31 expression in the DOX-treated group, along with a marked shift in morphometric measurements, a disordered ultrastructure, and overexpression of inflammatory genes (ERK, NF-κB, IL-6, and TNF-α), oxidative stress markers, and cardiac biomarkers. Both groups IV and V displayed reduced cardiac fibrosis or inflammation, restoration of the microstructure and ultrastructure of the myocardium, downregulation of inflammatory genes, markers of oxidative stress, and cardiac biomarkers, a notable decline in vimentin, and an uptick in CD-31 expression. In contrast to group IV, group V showed a considerable beneficial effect. CONCLUSION: Both OLE and BM-MSCs showed an ameliorating effect in rat models of DOX-induced cardiotoxicity, with BM-MSCs showing a greater influence than OLE.

Evaluation of nootropic activity of telmisartan and metformin on diazepam-induced cognitive dysfunction in mice through AMPK pathway and amelioration of hippocampal morphological alterations.

Cognitive impairments such as dementia are considered the biggest challenges for public health. Benzodiazepines are often prescribed for treatment of anxiety disorder but they are associated with elevated risk of dementia. The present study has been designed to evaluate the neuroprotective effect of telmisartan and metformin on diazepam-induced cognitive dysfunction in mice. Piracetam was used as an established nootropic agent. Mice were divided into 8 groups, group1; control group which received normal saline. groups 2, 3 and 4 were received telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. group 5; DZP group that injected with diazepam 2.5 mg/kg, groups 6, 7 and 8 were received diazepam 2.5 mg/kg + telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. All drugs were administrated for 15 successive days. Cognitive skills of the animals were examined with Elevated plus maze and Passive Shock Avoidance tests. Investigations of oxidative stress markers were performed. Gene expression levels of TNF-α, NFκB, Caspase 3 and AMPK were analyzed using RT-PCR. Histological and immunohistochemical techniques were performed in hippocampus using H&E, cresyl violet stain, anti GFAP and anti COX-2 immunostain. The study revealed that administration of diazepam increased initial and retention transfer latency as well as it decreased step down latency that means it caused memory impairment. There was a significant increase in hippocampal expression levels of TNF-α, NFκB, and Caspase 3 and downregulation of AMPK expression levels associated with increased neurodegeneration, astrocytes activation and COX-2 immunohistochemical staining. This study indicates that diazepam caused a decline in cognitive function depending on hippocampal activity. Telmisartan, a common antihypertensive agent and metformin, a traditional antidiabetic drug improved this cognitive dysfunction through their anti-oxidant and anti-inflammatory effect as they decreased initial and retention transfer latency as well as it increased step down latency. Also they decreased TNF-α, NFκB, and Caspase 3 and upregulated AMPK expression, moreover they ameliorated the hippocampal morphological alterations, GFAP and COX-2 immunoexpression.

Ameliorating effect of melatonin on mercuric chloride-induced neurotoxicity in rats.

Mercury is a highly toxic metal. It induces its toxicity via production of reactive oxygen species. Brain tissues are more susceptible to oxidative damage. Melatonin and its metabolites are free radical scavengers. The aim of this work is to elucidate the neuroprotective effect of melatonin on mercuric chloride-induced neurotoxicity in rats. Fifty male albino rats were used and divided into five groups. Group I acts as normal control. Group II (LD HgCl2) received mercuric chloride at a dose of 2 mg/kg. Group III (HD HgCl2) received HgCl2 at a dose of 4 mg/kg. Rats in group IV (LD HgCl2 +MLT) received HgCl2 2 mg/kg + Melatonin 5 mg/kg. Rats in group V (HD HgCl2+MLT) received HgCl2 4 mg/kg + Melatonin5 mg/kg. This study revealed that mercuric chloride decreased the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes and increased malondialdehyde levels. Toxicity of mercuric chloride lead to upregulation of the gene expression level vascular endothelial growth factor. HgCl2 induced fragmentation of rough endoplasmic reticulum, ballooning of Golgi apparatus, nuclear and cytoplasmic degeneration of pyramidal neurones of rat cerebral cortex. This neuronal damage caused by HgCl2 was significantly improved by melatonin.

Comparing the Effects of Febuxostat and Allopurinol in an Animal Model of Metabolic Syndrome.

INTRODUCTION: Recent studies highlighted the association of hyperuricemia and metabolic syndrome (MS). The aim of this study was to compare the beneficial effects of febuxostat versus allopurinol on the biochemical changes that occur in MS. METHODS: Forty adult male Sprague Dawley albino rats were used in the study. Insulin resistance and MS were induced by administration of a high-fructose diet for 8 weeks. Follow-up of changes in weight, blood pressure, serum biochemical parameters, serum antioxidant catalase, and glutathione peroxidase activities was done. At the end of the study, animals were sacrificed, and the thoracic aorta was isolated for in vitro study of the endothelial integrity. RESULTS: Allopurinol and febuxostat treatment induced significant reduction in body weight, systolic blood pressure, blood glucose, insulin, lipids, and improved kidney functions and endothelial integrity compared to nontreated rats. Febuxostat was more effective than allopurinol in normalizing serum fasting glucose, uric acid, catalase, and glutathione peroxidase activities. CONCLUSION: Xanthine oxidase inhibitors ameliorated the effects of MS. Febuxostat was mildly superior to allopurinol in lowering serum fasting glucose, lipids, uric acid, and antioxidant enzyme activities.

Relation between HLA-DP/DQ Polymorphisms, Serum IP-10 and Response to Direct Acting Antiviral Therapy among HCV Infected Patients.

HCV infection represents a worldwide health problem with many attempts to control. This study aimed to assess the relation between HLA-DQ-rs3920 SNP, HLA-DP-rs3077 SNP, serum IP-10 levels and response to direct acting antiviral (DAA) drugs among HCV infected Egyptian patients. The study included 100 HCV infected patients (received sofosbuvir, Daclatsvir and Ribavirin) and 50 apparently healthy volunteers as controls. Serological, hematological and viral investigations were done to all participants. Whole DNA was extracted, HLA-DQ-rs3920 SNP and HLA-DP-rs3077 SNP were evaluated using RT-PCR and serum IP-10 levels were determined. Higher frequencies of HLA-DQ rs3920 AG and HLA-DP rs3077 AA variants was observed among HCV infected patients (P<0.001* and P=0.029*, respectively). There was a statistically significant association between both genotypes and response to DAA. However, HLA-DQ rs3920 A allele was markedly expressed among non-responders group and could be correlated with resistance to DAA therapy. IP-10 levels were significantly decreased among the non-responder group with 95% sensitivity and 15% specificity. We concluded that HLA-DP-rs3077 and/or HLA-DQ-rs3920 SNP may represent independent predictors for susceptibility to infection and response to direct antiviral drugs among HCV infected Egyptian patients. Serum IP-10 could be a predictive marker for disease progression and response to DAA.

In vitro and in vivo growth inhibitory activities of cryptolepine hydrate against several Babesia species and Theileria equi.

Piroplasmosis treatment has been based on the use of imidocarb dipropionate or diminazene aceturate (DA), however, their toxic effects. Therefore, the discovery of new drug molecules and targets is urgently needed. Cryptolepine (CRY) is a pharmacologically active plant alkaloid; it has significant potential as an antiprotozoal and antibacterial under different in vitro and in vivo conditions. The fluorescence assay was used for evaluating the inhibitory effect of CRY on four Babesia species and Theileria equi in vitro, and on the multiplication of B. microti in mice. The toxicity assay was evaluated on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3), and human foreskin fibroblast (HFF) cell lines. The half-maximal inhibitory concentration (IC50) values of CRY on Babesia bovis, B. bigemina, B. divergens, B. caballi, and T. equi were 1740 ± 0.377, 1400 ± 0.6, 790 ± 0.32, 600 ± 0.53, and 730 ± 0.025 nM, respectively. The toxicity assay on MDBK, NIH/3T3, and HFF cell lines showed that CRY affected the viability of cells with a half-maximum effective concentration (EC50) of 86.67 ± 4.43, 95.29 ± 2.7, and higher than 100 µM, respectively. In mice experiments, CRY at a concentration of 5 mg/kg effectively inhibited the growth of B. microti, while CRY-atovaquone (AQ) and CRY-DA combinations showed higher chemotherapeutic effects than CRY alone. Our results showed that CRY has the potential to be an alternative remedy for treating piroplasmosis.

Syzygium aromaticum L. (Myrtaceae): Traditional Uses, Bioactive Chemical Constituents, Pharmacological and Toxicological Activities.

Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides, saponins, flavonoids, steroids, tannins, alkaloids, terpenes, etc. Syzygium aromaticum (clove) is a traditional spice that has been used for food preservation and possesses various pharmacological activities. S. aromaticum is rich in many phytochemicals as follows: sesquiterpenes, monoterpenes, hydrocarbon, and phenolic compounds. Eugenyl acetate, eugenol, and ß-caryophyllene are the most significant phytochemicals in clove oil. Pharmacologically, S. aromaticum has been examined toward various pathogenic parasites and microorganisms, including pathogenic bacteria, Plasmodium, Babesia, Theileria parasites, Herpes simplex, and hepatitis C viruses. Several reports documented the analgesic, antioxidant, anticancer, antiseptic, anti-depressant, antispasmodic, anti-inflammatory, antiviral, antifungal, and antibacterial activity of eugenol against several pathogenic bacteria including methicillin-resistant Staphylococcusepidermidis and S. aureus. Moreover, eugenol was found to protect against CCl4-induced hepatotoxicity and showed a potential lethal efficacy against the multiplication of various parasites including Giardia lamblia, Fasciolagigantica, Haemonchuscontortus, and Schistosomamansoni. This review examines the phytochemical composition and biological activities of clove extracts along with clove essential oil and the main active compound, eugenol, and implicates new findings from gas chromatography-mass spectroscopy (GC-MS) analysis.