scholarly journals The Pre-Conception Maternal Exposure To Sofosbuvir Impacts The Mitochondrial Biogenesis In Prenatal Fetal Tissues: Experimental Study On Rats

Author(s):  
Sara. A. Shaker ◽  
Maryam. M. Abdel-Aziz ◽  
Rana HM. Khafaga ◽  
Hala A. Hafez ◽  
Maher A. Kamel ◽  
...  

Abstract Hepatitis C virus (HCV) infection is a global public health problem and Egypt has the highest HCV prevalence worldwide. Hence, global efforts target to eliminate HCV by 2030. Sofosbuvir is a nucleotide analogue inhibitor of HCV polymerase essential for viral replication. Animal studies prove that Sofosbuvir metabolites cross the placenta and are excreted in the milk of nursing animals. We aimed to investigate the possible effects of preconception maternal exposure to Sofosbuvir on the mitochondrial biogenesis in prenatal fetal liver, skeletal muscle and placental tissues using female rats. The study was conducted on 20 female albino rats classified into 2 groups, control group including 10 healthy rats receiving placebo, and exposed group including 10 rats receiving 4 mg/kg of Sofosbuvir. At the end of the 3-month treatment period, pregnancy was induced in both groups by mating with healthy male rats overnight. At gestational day 17, all pregnant female rats were sacrificed. Each fetus was dissected to obtain the fetal liver, skeletal muscle and placental tissues. The results of our study indicated that the preconception exposure of young female rats to Sofosbuvir affects pregnancy outcomes, decreases fertility, and impacts mitochondrial biogenesis and functions in prenatal fetal liver, skeletal muscle and placental.

2017 ◽  
Vol 117 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Yanping Huang ◽  
Shixing Gao ◽  
Guo Jun ◽  
Ruqian Zhao ◽  
Xiaojing Yang

AbstractThe present study aimed to investigate the effects of maternal dietary butyrate supplementation on energy metabolism and mitochondrial biogenesis in offspring skeletal muscle and the possible mediating mechanisms. Virgin female rats were randomly assigned to either control or butyrate diets (1 % butyrate sodium) throughout gestation and lactation. At the end of lactation (21 d), the offspring were killed by exsanguination from the abdominal aorta under anaesthesia. The results showed that maternal butyrate supplementation throughout gestation and lactation did not affect offspring body weight. However, the protein expressions of G-protein-coupled receptors (GPR) 43 and 41 were significantly enhanced in offspring skeletal muscle of the maternal butyrate-supplemented group. The ATP content, most of mitochondrial DNA-encoded gene expressions, the cytochrome c oxidase subunit 1 and 4 protein contents and the mitochondrial DNA copy number were significantly higher in the butyrate group than in the control group. Meanwhile, the protein expressions of type 1 myosin heavy chain, mitochondrial transcription factor A, PPAR-coactivator-1α (PGC-1α) and uncoupling protein 3 were significantly increased in the gastrocnemius muscle of the treatment group compared with the control group. These results indicate for the first time that maternal butyrate supplementation during the gestation and lactation periods influenced energy metabolism and mitochondrial biogenesis through the GPR and PGC-1α pathways in offspring skeletal muscle at weaning.


Author(s):  
Marijana Andjic ◽  
Nevena Draginic ◽  
Kristina Radoman ◽  
Jovana Jeremic ◽  
Tamara Nikolic Turnic ◽  
...  

Abstract. Considering that sex related differences in cardiac response to flaxseed (FSO) and evening primrose oil (EPO) are insufficiently known present investigation assessed the effect of these two oils, on the cardiac function of isolated rat hearts and the possible role of sex in this. The present study was carried out on 60 adult male Wistar albino rats randomly divided into 6 groups: male rats treated with EPO, dose of 10 mg/kg/day; female rats treated with EPO, dose of 10 mg/kg/day; male rats treated with FSO, dose of 300 mg/kg/day; female rats treated with FSO, dose of 300 mg/kg/day; control group of female rats treated with regular laboratory diet for animals; control group of male rats treated with regular laboratory diet for animals. Using the Langendorff technique, markers of the heart function were evaluated: the maximum and minimum rates of pressure development in the left ventricle (LV; dP/dtmax, dP/dtmin), systolic and diastolic left ventricular pressure (SLVP, DLVP, respectively), heart rate (HR) and coronary flow (CF). Male rats treated with EPO had significantly higher (p = 0.016) mean values of dP/dtmax, dP/dtmin, SLVP and DLVP (average increase for all CPPs 20%, 25%, 30% and 110%, respectively), compared to the group of male rats treated with FSO (p = 0.914). Our study results indicate that both types of PUFA oils only slightly changed the function of the isolated rat heart in male but not in female rats. Nevertheless, the difference between oil treatments was found in male rats who had stronger cardiac response after supplementation with EPO.


Author(s):  
А.А. Симанкова ◽  
Е.Н. Сазонова ◽  
О.А. Лебедько

Цель исследования - анализ влияния d/m-агониста даларгина (Tyr - D-Ala - Gly - Phe - Leu - Arg) на морфофункциональные показатели головного мозга у половозрелых белых крыс Вистар, перенесших антенатальную гипоксию. Методика. Крысы-самки подвергались воздействию гипобарической гипоксии с 15-х по 19-е сут. гестации. Потомство было разделено на 2 группы: 1) животным группы «Антенатальная гипоксия» (n = 12) интраперитонеально вводили 0,1 мл физиологического раствора с 2-х по 6-е сут. жизни; 2) животным группы «Антенатальная гипоксия + даларгин» (n = 17) в те же сроки интраперитонеально вводили даларгин в дозировке 100 мкг/кг. Группа «Контроль» (n = 25) включала потомство крыс-самок, не подвергавшихся действию гипоксии в период гестации. В гистологических препаратах головного мозга 60-суточных крыс-самцов исследуемых групп определяли площадь ядер и ядрышек нейронов II и V слоев неокортекса и поля СА1 гиппокампа. Активность процессов свободнорадикального окисления в гомогенатах головного мозга определяли методом хемилюминисценции. Поведенческие реакции оценивали в тестах «Открытое поле» и «Приподнятый крестообразный лабиринт». Результаты. У животных группы «Антенатальная гипоксия» выявлено уменьшение массы тела и массы головного мозга; уменьшение числа ядрышек в нейронах II слоя неокортекса и гиппокампа, уменьшение площади ядер нейронов V слоя неокортекса и снижение площади ядрышек нейронов всех исследованных зон; повышение локомоторной активности; активация свободнорадикального окисления в гомогенатах мозга. Введение даларгина уменьшало морфофункциональные церебральные последствия антенатальной гипоксии. Заключение. Показан эффект даларгина для коррекции отдаленных церебральных последствий перенесенной антенатальной гипоксии в эксперименте. The aim of the study was to analyze the effect of d/m-agonist dalargin (Tyr-D-Ala-Gly-Phe-Leu-Arg) on brain morphology and function in mature albino rats exposed to antenatal hypoxia. Methods. Female rats were exposed to hypobaric hypoxia from gestation day 15 to day 19 day. The offspring was divided into 2 groups: 1) the first group, antenatal hypoxia (n = 12), where rats were injected with 0.1 ml of saline from 2 to 6 days of life, 2) the second group, antenatal hypoxia + dalargin (n = 17), where rats were injected with the peptide dalargin (100 mg/kg, i.p.) from 2 to 6 days of life. The control group (n = 25) included offspring of intact female rats. The size of neuronal nuclei and nucleoli in neocortical layers II and V and hippocampal area CA1 were measured on histological slides of the brain from 60-day old male rats. Intensity of free radical oxidation was determined by chemiluminescence in brain homogenates. Rat behavior was evaluated using the open field test and the elevated plus-maze test. Results. Antenatal hypoxia decreased body weight and weight of cerebral hemispheres in 60-day old male albino rats compared with the control. Antenatal hypoxia decreased the number of neuronal nucleoli in layer II of the neocortex and hippocampal area CA1, reduced neuronal nucleus size in layer V of the neocortex and the total area of neuronal nucleoli in all examined brain areas of 60-day-old male albino rats. Animals of this experimental group displayed increased motor activity. The chemiluminescence study of brain homogenates from 60-day-old animals showed increased free radical generation in brain tissues. Administration of dalargin reduced the morphofunctional cerebral consequences of antenatal hypoxia. Conclusion. Dalargin can be used for correcting long-term cerebral consequences of antenatal hypoxia.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040305
Author(s):  
Chao Li ◽  
Ping Zhou ◽  
Yixi Cai ◽  
Bin Peng ◽  
Yongfang Liu ◽  
...  

IntroductionGestational diabetes mellitus (GDM) is a common gestational disease and an important global public health problem. GDM may affect the short-term and long-term health of offspring, but the associations between GDM and the neurodevelopment of offspring of mothers with GDM (OGDM) are still unclear, and studies based on the Chinese population are lacking. We aim to determine the associations between GDM and the neurodevelopment of OGDM by studying a cohort of OGDM and offspring of non-GDM mothers.Methods and analysisThe single-centre prospective cohort study is being conducted in China over 7 years. A total of 490 OGDM (GDM group) and 490 fromof healthy mothers (control group) will be enrolled during the same period. Baseline characteristics, neuropsychological development scores and clinical data at specific time points (at 0, 1, 3, 6, 12, 24, 36, 48, 60 and 72 months old) will be collected from the children in both groups until the age of 6 years. The associations between GDM and the neurodevelopment of OGDM from infancy to preschool age will be analysed using a multiple linear regression model adjusted for confounders. In addition, we will compare longitudinal data to further assess the effects of GDM on neurodevelopmental trajectories.Ethics and disseminationThe study has been approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University (Approval Number: (2019) Institutional Review Board (IRB) (STUDY) No. 85). The findings of this study will be disseminated through open access journals, peer-reviewed journals and scientific meetings.Trial registration numberNCT03997396.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murtala Akanji Abdullahi ◽  
Elijah Oladapo Oyinloye ◽  
Akinyinka Alabi ◽  
Aderonke Adeyinka Aderinola ◽  
Luqman Opeyemi Ogunjimi ◽  
...  

Abstract Objectives Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. Methods Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. Results The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. Conclusions The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.


2021 ◽  
pp. 39-45
Author(s):  
Nura I. Al-Zail ◽  
Salah F. Kamies

Pyrethroid cyhalothrin (PC) is an insecticide that is used worldwide for pest control in agriculture and household use. Samoa extract (SE) is a potent antioxidant protecting cells from oxidative stress. The present study investigates the protective and therapeutic effect of SE on PC-induced changes in sperm quality in male rats. Fifty adult male albino rats were divided into five groups: group I: served as control; group II: received PC i.p. only (6.2 mg/kg b.wt.); group III: received SE only (100 mg/kg b.wt., p.o.) for eight weeks; group IV: received SE as a protective agent daily for eight weeks, then followed by the administration of PC (i.p.) three times a week for two weeks; group V: exposed to PC (i.p.) three times a week for two weeks, then treated with the SE daily for 8 weeks. Results showed that PC caused markedly impaired sperm quality (a count, viability, motility, and abnormality). Compared to PC-treated animals, SE in the protective group markedly restored the alteration of sperm indices. However, SE in the curative group was found to be less effective in restoring PC-induced alterations. In conclusion, the data of this study revealed that the SE as a protective agent is more effective than as a therapeutic agent. Keywords: Samoa; Pyrethroid; Sperm quality; Rat


2015 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Barnabé Lucien Nkono Ya Nkono ◽  
Selestin Dongmo Sokeng ◽  
Paul Désiré Dzeufiet Djomeni ◽  
Frida Longo ◽  
Pierre Kamtchouing

<p><strong>Methodology:</strong> Wistar rats were randomly assigned into eight groups of five animals each: four male groups and four female groups. Each sex group had a control group receiving distilled water and three test groups receiving 200, 500 and 1000mg/kg respectively. Animal’s body weights were recorded on the first day and once a week for the four experiment weeks. The hematological analysis included total WBC count, total RBC count, Hb, %HCT, MCV, MCH and MCHC. Biochemical/serum profile studies include TG, TC, ALT, AST, urea and TP. Tissue specimens of the liver, kidney and lung were subjected to histological examination using standard hematoxylin-eosin staining.</p><p><strong>Results:</strong> In male rats, aqueous extract showed significant decreases in relative weight of liver with extreme significance P&lt;0.001 at a dose of 200mg/kg (vs. control group), P&lt;0.001 of lung at all the doses, P&lt;0.05 (200 and 500mg/kg) and P&lt;0.01 (1000mg/kg) in heart weight. In relative kidney weight, only the dose of 1000mg/kg showed a significant increase vs. normal control male rats. Unlike male rats, only relative kidney weight in female rats was significantly different from the control group in a dose-dependent manner. The aqueous extract treated male groups showed significant increases P&lt;0.001 (1000mg/kg) of total WBC count and MCHC, significant decreases of %HTC (dose response manner), P&lt;0.05 total RBC count (at doses of 500 and 1000mg/kg) and Hb P&lt;0.01 (500mg/kg) vs. normal male rats. In female rats, the haematological study showed significant increase P&lt;0.01 of total WBC count (at the doses of 500 and 1000mg/kg), significant decreases P&lt;0.05 and P&lt;0.01 of total RBC respectively at the doses of 200 and 1000mg/kg, significant decrease of Hb with extreme significance P&lt;0.001 at the dose 1000mg/kg, %HTC also decrease dose response manner vs. control female rats. Biochemical study showed in male rats significant decreases in level of TG P&lt;0.001 (at the doses of 200 and 500mg/kg) and urea, although it showed any dose-dependent effect vs. control male rats. AST also decreases (P&lt;0.05) in male rats at the dose of 200mg/kg but significantly increase P&lt;0.001 at the dose of 500mg/kg. In the female rats, biochemical study revealed significant increases in level of TG P&lt;0.001 and urea P&lt;0.01 at the dose of 200mg/kg and significant decreases in level of TG P&lt;0.01, AST P&lt;0.05 and urea P&lt;0.05 at the dose of 500mg/kg (vs. control female rats). Microscopically, there were mild hepatic and renal tissue injuries supporting the hematological analysis.</p><p><strong>Conclusion:</strong> The results indicated that aqueous extract of <em>Alstonia boonei</em> De Wild is toxic in high doses.</p>


2018 ◽  
Vol 38 (5) ◽  
pp. 499-509 ◽  
Author(s):  
H Bouzenna ◽  
N Samout ◽  
S Dhibi ◽  
S Mbarki ◽  
S Akermi ◽  
...  

The present study is planned to examine the antioxidant activity (AA) and the protective effect of the essential oil of Citrus limon (EOC) against aspirin-induced histopathological changes in the brain, lung, and intestine of female rats. For this purpose, 28 albino rats were classified to control group (group C), aspirin group (group A), EOC group (group EOC), and pretreatment with EOC and treated with aspirin group (group EOC + A). The antioxidant activities of EOC were evaluated by three different assays including reducing power, β-carotene, and scavenging of hydrogen peroxide (H2O2). Our results found that EOC represents, respectively (0.064 ± 0.013 and 0.027 ± 00 mg Quer E/100 µL), of flavonoid and flavonol. Then, it exhibited a potential activity of reducing power (at 300 mg/mL, which was found to be 0.82 ± 0.07), β-carotene-linoleic acid (AA% = 69.28 ± 3.5%), and scavenging of H2O2 (IC50 = 0.23 ± 0.008 mg/mL). In vivo, aspirin given to rats at the dose of 600 mg/kg body weight induced histomorphological damage in brain, lung, and intestine. However, our data found that the pretreatment with EOC offered a significant protection against the injury induced by aspirin. It can be concluded that the protective effect of EOC can be due to its antioxidant activities.


Author(s):  
I. S. Esua ◽  
U. U. Uno ◽  
U. B. Ekaluo

Background and Aim: Tramadol is a potent analgesic effective in the treatment of mild to severe pains. However, the use of the drug can pose a threat to other organs and systems. Therefore, this study evaluated the effect of graded doses of tramadol on sperm profile of male albino rats. Materials and Methods: Eighteen male rats were divided into three groups (A, B and C) using completely randomized design (CRD) with six rats in each group. Rats in group A served as the control group and were given just food and water while groups B and C were given tramadol at 50 and 100 mg/kg body weight (BW) respectively, daily for the period of 65 days. The treatment was administered via oral gavage and at the end of the treatments, the rats were sacrificed. Immediately after sacrifice, a puncture was made in the epididymis with a sterile pin and examined for semen pH. The epididymes were processed for epididymal sperm motility, viability, count and sperm head abnormality. Results: There was no significant difference in the weight of testes and semen pH. Sperm viability, sperm motility, sperm count and weight of epididymes significantly reduced (p<0.05) in tramadol treated animals when compared with the control. Results also indicated statistically significant (p<0.05) increase in sperm head abnormalities in rats treated with tramadol when compared with the control. Conclusion: The results obtained from this study reveal that tramadol has negative effects on weight of epididymes, sperm count, sperm viability, sperm motility and sperm head abnormalities in male albino rat as mammalian models in a dose dependent manner.


2017 ◽  
Vol 2 (2) ◽  
pp. 112-120
Author(s):  
Nazar Mohammed Shareef Mahmood ◽  
Sarkawt Hamad Ameen Hamad ◽  
Dlshad Hussein Hassan ◽  
Karwan Ismael Othman

The toxicity of lead acetate (L. A.) concerned to public health disruptor due to its persistence in the environment and it has the adverse influence on the human and animal health as well. It causes physiological,biochemical, and neurological dysfunctions in humans. Histologically it has a negative effect on the liver which is considered one of the major target organs where acts as detoxification machine by elimination the toxic substance from the blood in rich with it.  As well as it affects kidneys that are the two of the most filtering organs. Therefore the present study was aimed to investigate the histopathological effect of L.A. on liver and kidney tissues in male rats. Twenty male rats involved in the study were equally and randomly divided into two groups each of them involved 10 animals. Group I (castrated rats) and Group II (control) each group received 80mg/L of lead acetate dissolved in one liter distilled water by drinking for 15 days. Histological sections showed some alterations including abnormal architecture, cell degeneration, nuclear degeneration, hyperchromatic hepatocytes, immune cells, degeneration in tubules, dilation in sinusoids, dilation in central vein of liver increased bowman's space glomerular atrophy degeneration of tubular cells in liver and kidney tissues of rats in castrated rats from control group. But the size of degenerated tissue was more severe in castrated male rats. It was concluded that the castration process could produce a hypogonadism and decreased testosterone which owns many receptors in kidney and liver may produce adverse influence with L.A. administration.


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