The effects of trimetazidine on lipopolysaccharide-induced oxidative stress in mice

The effects of trimetazidine, a novel anti-ischemic agent, on the development of oxidative stress induced in mice with lipopolysaccharide endotoxin were investigated. The drug was administered orally once daily at doses of 1.8, 3.6 or 7.2 mg/kg for two days prior to intraperitoneal (i.p.) injection of lipopolysaccharide E (200 μg/kg) and at time of endotoxin administration. Mice were euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) concentrations were measured in brain and liver. The administration of lipopolysaccharide increased oxidative stress in both the brain and liver tissue. MDA increased by 33.9 and 107.1 %, GSH decreased by 23.9 and 84.3 % and nitric oxide increased 70.3 and 48.4 % in the brain and liver, respectively. Compared with the lipopolysaccharide control group, brain MDA decreased by 26.2 and 36.7 %, while GSH increased by 18.2 and 25.8 % after the administration of trimetazidine at 3.6 and 7.2 mg/kg, respectively. Brain nitric oxide decreased by 45.3, 50.8 and 57.0 % by trimetazidine at 1.8, 3.6 and 7.2 mg/kg, respectively. In the liver, MDA decreased by 18.7, 30.7 and 49.4 % and GSH increased by 150.3, 204.8 and 335.4 % following trimetazidine administration at 1.8, 3.6 and 7.2 mg/kg. Meanwhile, nitric oxide decreased by 17.3 % by 7.2 mg/kg of trimetazidine. These results indicate that administration of trimetazidine in the presence of mild systemic inflammatory response alleviates oxidative stress in the brain and liver

The effect of different antidepressant drugs of oxidative stress after lipopolysaccharide administration in mice

This study investigated the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine, sertraline, fluvoxamine and the tricyclic antidepressant (TCA) impiramine on oxi-dative stress in brain and liver induced by lipopolysaccharide administration in mice. Each drug was administered subcutaneously at doses of 10 or 20 mg/kg, for two days prior to in-traperitoneal (i.p.) administration of lipopolysaccharide E (LPS: 200 μg/kg). Mice were euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation (malondial-dehyde; MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) concentrations were measured in brain and liver. Results: The administration of lipopolysaccharide increased oxidative stress in brain and liv-er; it increased brain MDA by 36.1 and liver MDA by 159.8 %. GSH decreased by 34.1 % and 64.8 % and nitric oxide increased by 78.7 % and 103.8 % in brain and liver, respectively. In brain, MDA decreased after the administration of sertraline and by the lower dose of fluo-xetine or fluvoxamine, but increased after the higher dose of imipramine. Reduced glutathione increased after sertraline, fluvoxamine and the lower dose of fluoxetine or imipramine. Nitric oxide decreased by sertraline, fluoxetine, fluvoxamine and by the lower dose of imipramine. In the liver, all drugs decreased MDA and increased GSH level. Nitric oxide is decreased by sertraline, fluvoxamine and by the lower dose of fluoxetine or imipramine. It is concluded that, during mild systemic inflammatory illness induced by peripheral bacterial endotoxin in-jection, the SSRIs fluoxetine, sertraline and fluvoxamine reduced, while the TCA impiramine increased oxidative stress induced in the brain. The SSRIs as well as imipramine reduced oxi-dative stress due to lipopolysaccharide in liver tissue

Hepatoprotective effects of citric acid and aspartame on carbon tetrachloride-induced hepatic damage in rats

The aim of this study was to investigate the effect of citric acid or the sweetening agent aspartame on the CCl4-induced hepatic injury in rats. Citric acid (10 mg/kg, 100 mg/kg or 1000 mg/kg), aspartame (0.625 or 1.25 mg/kg) or silymarin (25 mg/kg) was given once daily orally simultaneously with CCl4 and for one week thereafter. The administration of citric acid at 100 mg/kg or 1000 mg/kg to CCl4-treated rats reduced elevated plasma ALT by 44.1-63.3 %, AST by 47.8-70.6 %, ALP by 41.7-67.2 %, respectively compared to controls. Aspartame at 0.625 or 1.25 mg/kg reduced plasma ALT by 39.8-52.0 %, AST by 43.2-52.4 % and ALP by 50.0-68.5 %, respectively. Meanwhile, silymarin at 25 mg/kg reduced ALT, AST and ALP levels by 52.7, 62.2 and 64.7 %, respectively. On histology, citric acid at 1000 mg/kg resulted in near normalization of liver tissue. Vacuolar degeneration and necrosis were markedly reduced by 1.25 mg/kg aspartame. These results indicate that treatment with citric acid or the sweetening agent aspartame protects against hepatocellular necrosis induced by CCl4

Spontaneous ovulation and pregnancy in women with polycystic ovarian disease; a cross sectional study

Background: Polycystic ovary disease (PCOD) is the most common endocrine disorder in women of reproductive age, with a prevalence of approximately 5-10%. This study aims to assess the rate of spontaneous ovulation and pregnancy in patients. The present study was a cross sectional study conducted at Woman's Health Hospital, Assiut University, Assiut, Egypt.Methods: The current study was a cross sectional study carried out in Assiut Women's Health Hospital between the 1st October 2016 and 31st July 2017. The patients were selected as infertile patients with PCOD. The patient ages range between 20 and 35 years. The BMI is between 18 and 30 Kg/m2. The main outcome measure was the rate of spontaneous ovulation and spontaneous pregnancy in the 3 cycles.Results: The mean age of the study participants was 26.64±4.59 years and the mean BMI was 24.46±2.62Kg/m2. The sonographic ovarian volume was 12.47±0.69 mm3 for the right ovary and 12.74±0.73 mm3 for the left ovary. No difference in the serum FSH, LH, FSH/LH ratio and prolactin over the 3 consecutive cycles. The rate of spontaneous ovulation in the 3 cycles was 6 women (8.6%) and 2 cases (2.8%) became pregnant spontaneously during the study period. There is no statistical significant difference between ovulating and non-ovulating women according to the BMI and ovarian volume.Conclusions: The present study concluded that the rate of spontaneous ovulation was 8.6% in women with PCOD within 3 cycles with no adverse effects of drugs or surgical interference

Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine

Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice

Isolation of biologically active metabolites from Bougainvillea spectabilis Willd. cultivated in Egypt

Bougainvillea spectabilis Willd.  is an ornamental plant cultivated in tropical, subtropical regions and other places as Egypt. The present study aimed to perform bioassay guided fractionation and isolation of some of the bioactive compounds from the Egyptian cultivate. The total ethanol extracts of the leaves (T.ET.L.), stems (T.ET.S.) and flowers (T.ET.F.) were screened for some pharmacological activities viz. in vivo anti-oxidant and anti-hepatotoxic, in addition to in vitro cytotoxic activities. The anti-oxidant effect was assessed by measuring serum glutathione level (GSH) in alloxan-induced diabetic rats. The anti-hepatotoxic activity was evaluated via measuring serum markers level viz. alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl4-induced hepatotoxicity in rats. In vitro cytotoxicity of the different extracts was estimated for liver cancer cell line (HEPG2) adopting Sulforhodamine B stain assay. T.ET.L. exhibited significantly potent anti-oxidant and anti-hepatotoxic activities, while T.ET.S. showed the highest cytotoxic activity. Through biological guided fractionation, leaves and stems were subjected to successive solvent extraction, whereas the leaves ethyl acetate (Et.Ac.L.) and the stems ethanol 70% (Et.70%S.) extracts showed highly potent activities. Thus, different chromatographic techniques were performed on Et.Ac.L. and Et.70%S. extracts leading to the isolation of five bioactive metabolites. Three flavonoids were isolated from Et.Ac.L.; genistein-7-O-rutinoside (1), formononetin-7-O-rutinoside (2) and myricetin (3), while orobol-7-O-glucoside (4) and hesperidin (5) were isolated from Et.70%S. This work demonstrated the importance of the plant as a promising anti-oxidant, anti-hepatotoxic and cytotoxic product for nutraceutical use

Guidelines for the establishment and functioning of Animal Ethics Commitees (Institutional Animal Care and Use Committees) in Africa.

Animals are used for scientific purposes across Africa to benefit humans, animals or the environment. Nonetheless, ethical and regulatory oversight remains limited in many parts of the continent. To strengthen this governance framework, the Pan-African Network for Laboratory Animal Science and Ethics brought together experts from 12 African countries to create an Africa-centric practical guide to facilitate the establishment and appropriate functioning of Institutional Animal Ethics Committees across Africa. The Guidelines are based on universal principles for the care and use of sentient animals for scientific purposes, with consideration of the cultural, religious, political and socio-economic diversity in Africa. They focus on 11 key elements, including responsibilities of institutions and of the Institutional Official; composition of the Committee; its responsibilities, functioning and authority; ethical application and review processes; oversight and monitoring of animal care and use and of training and competence; quality assurance; and the roles of other responsible parties. The intent is for African institutions to adopt and adapt the guidelines, aligning with existing national legislation and standards where relevant, thus ensuring incorporation into practice. More broadly, the Guidelines form an essential component of the growing discourse in Africa regarding moral considerations of, and appropriate standards for, the care and use of animals for scientific purposes. The increased establishment of appropriately functioning animal ethics committees and robust ethical review procedures across Africa will enhance research quality and culture, strengthen societal awareness of animals as sentient beings, improve animal well-being, bolster standards of animal care and use, and contribute to sustainable socio-economic development

Identifying structures, processes, resources and needs of research ethics committees in Egypt

<p>Abstract</p> <p>Background</p> <p>Concerns have been expressed regarding the adequacy of ethics review systems in developing countries. Limited data are available regarding the structural and functional status of Research Ethics Committees (RECs) in the Middle East. The purpose of this study was to survey the existing RECs in Egypt to better understand their functioning status, perceived resource needs, and challenges.</p> <p>Methods</p> <p>We distributed a self-administered survey tool to Egyptian RECs to collect information on the following domains: general characteristics of the REC, membership composition, ethics training, workload, process of ethics review, perceived challenges to effective functioning, and financial and material resources. We used basic descriptive statistics to evaluate the quantitative data.</p> <p>Results</p> <p>We obtained responses from 67% (12/18) of the identified RECs. Most RECs (10/12) have standard operating procedures and many (7/12) have established policies to manage conflicts of interests. The average membership was 10.3 with a range from 7-19. The predominant member type was physicians (69.5% of all of the REC members) with little lay representation (13.7%). Most RECs met at least once/month and the average number of protocols reviewed per meeting was 3.8 with a range from 1-10. Almost three-quarters of the members from all of the 12 RECs indicated they received some formal training in ethics. Regarding resources, roughly half of the RECs have dedicated capital equipment (e.g., meeting room, computers, office furniture, etc); none of the RECs have a formal operating budget. Perceived challenges included the absence of national research ethics guidelines and national standards for RECs and lack of ongoing training of its members in research ethics.</p> <p>Conclusion</p> <p>Our study documents several areas of strengths and areas for improvements in the operations of Egyptian RECs. Regarding strengths, many of the existing RECs meet frequently, have a majority of members with prior training in research ethics, and have written policies. Regarding areas for improvements, many RECs should strive for a more diverse membership and should receive more financial resources and administrative support personnel. We recommend that RECs include more individuals from the community and develop a continuing educational program for its members. Institutional officials should be aware of the resource capacity needs of their RECs.</p