scholarly journals Neurobehavioral and Ultrastructural Changes Induced by Phytosynthesized Silver-Nanoparticle Toxicity in an In Vivo Rat Model

Nanomaterials ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Razvan Vlad Opris ◽  
Vlad Toma ◽  
Alina Mihaela Baciu ◽  
Remus Moldovan ◽  
Bogdan Dume ◽  
...  

(1) Background: The study aimed to assess neurobehavioral, ultrastructural, and biochemical changes induced by silver nanoparticles synthesized with Cornus mas L. extract (AgNPs-CM) in rat brains. (2) Methods: The study included 36 male adult rats divided into three groups. Over a period of 45 days, AgNPs-CM (0.8 and 1.5 mg/kg b.w.) were administered daily by gavage to two of the groups, while the control group received the vehicle used for AgNP. After treatment, OFT and EPM tests were conducted in order to assess neurobehavioral changes. Six of the animals from each group were sacrificed immediately after completion of treatment, while the remaining six were allowed to recuperate for an additional 15 days. Transmission electron microscopy (TEM), GFAP immunohistochemistry, and evaluation of TNFα, IL-6, MDA, and CAT activity were performed on the frontal cortex and hippocampus. (3) Results: Treated animals displayed a dose- and time-dependent increase in anxiety-like behavior and severe ultrastructural changes in neurons, astrocytes, and capillaries in both brain regions. Immunohistochemistry displayed astrogliosis with altered cell morphology. TNFα, IL-6, MDA, and CAT activity were significantly altered, depending on brain region and time post exposure. (4) Conclusions: AgNPs-CM induced neurobehavioral changes and severe cell lesions that continued to escalate after cessation of exposure.

1993 ◽  
Vol 128 (3) ◽  
pp. 268-273 ◽  
Author(s):  
René Habert

The acute in vivo testosterone response to LH stimulation and its change during late fetal life were determined in the rat. In 18.5-day-old fetuses, testicular testosterone content was increased in a dose-and time-dependent manner after fetal subcutaneous LH injection. The maximum response was small: the testicular content and plasma concentration were increased by 200% and 2 50% over basal values respectively, while they were increased 1100% and 1200% in adult rats. Similarly, comparable low responses were obtained after subcutaneously injecting the fetuses with human chorionic gonadotropin (hCG) and after injecting LH into the vitelline vein. Between days 18.5 and 21.5 of fetal life, the testosterone levels in the testis and plasma of uninjected or PBS-injected fetuses decreased and were comparable in both groups. In maximally LH-stimulated fetuses, the testicular content did not change with age, and plasma concentration was lower on day 21.5 than on day 18.5. Since the number of Leydig cells increases 1.5 to 2-fold between days 18.5 and 21.5, these results show an age-related decrease in basal and maximally LH-stimulated in vivo testosterone secretions per Leydig cell during late fetal life.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1519 ◽  
Author(s):  
Elena Oliveros ◽  
Enrique Vázquez ◽  
Alejandro Barranco ◽  
María Ramírez ◽  
Agnes Gruart ◽  
...  

Sialic acids (Sia) are postulated to improve cognitive abilities. This study evaluated Sia effects on rat behavior when administered in a free form as N-acetylneuraminic acid (Neu5Ac) or conjugated as 6′-sialyllactose (6′-SL). Rat milk contains Sia, which peaks at Postnatal Day 9 and drops to a minimum by Day 15. To bypass this Sia peak, a cohort of foster mothers was used to raise the experimental pups. A group of pups received a daily oral supplementation of Neu5Ac to mimic the amount naturally present in rat milk, and another group received the same molar amount of Sia as 6′-SL. The control group received water. After weaning, rats were submitted to behavioral evaluation. One year later, behavior was re-evaluated, and in vivo long-term potentiation (LTP) was performed. Brain samples were collected and analyzed at both ages. Adult rats who received Sia performed significantly better in the behavioral assessment and showed an enhanced LTP compared to controls. Within Sia groups, 6′-SL rats showed better scores in some cognitive outcomes compared to Neu5Ac rats. At weaning, an effect on polysialylated-neural cell adhesion molecule (PSA-NCAM) levels in the frontal cortex was only observed in 6′-SL fed rats. Providing Sia during lactation, especially as 6′-SL, improves memory and LTP in adult rats.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Başak Akça ◽  
Aysun Ankay Yılbaş ◽  
Filiz Üzümcügil ◽  
Berkem Büyükakkuş ◽  
Elham Bahador Zırh ◽  
...  

Abstract Background Intraarticular injections are widely used to provide pain relief after arthroscopic procedures and minimize the use of opioids. Dexmedetomidine has been proven to potentiate pain relief and postpone the demand for the first analgesic drug when it is used intraarticularly following arthroscopic knee procedures. However, the effects of dexmedetomidine on articular structures have not yet been evaluated. Our aim was to determine the effects of intraarticular dexmedetomidine injection on articular structures such as cartilage and synovium. Design Animal study. Methods Twenty adult rats (Sprague-Dawley) were enrolled in the study. Following appropriate aseptic and anesthetic conditions, dexmedetomidine (100 mcg/ml) (0.25 ml) was injected into the right knee joint (the study group) and normal saline solution (0.25 ml) into the left knee joint (the control group) of the rats. Four rats were sacrificed from each group on days 1, 2, 7, 14, and 21, and knee joint samples were obtained. Histologists evaluated the articular and periarticular regions and the synovium using histological sections, and a five-point scale was used to grade the inflammatory changes in a blinded manner. Results The groups were found to be similar in terms of median congestion scores, edema and inflammation scores, subintimal fibrosis, neutrophil activation and cartilage structure at each of the time intervals. Conclusion In our placebo-controlled, in vivo trial, the intraarticular use of dexmedetomidine seemed to be safe with respect to the studied histopathological parameters. However, complementary studies investigating the histopathological effects, analgesic dosage and adverse effects of dexmedetomidine on damaged articular structure models are needed.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3728-3728
Author(s):  
Lapo Alinari ◽  
Qing Liu ◽  
Ching-Shih Chen ◽  
Fengting Yan ◽  
James T Dalton ◽  
...  

Abstract Abstract 3728 Poster Board III-664 Over-expression of Cyclin D1 and constitutive phosphorylation of Akt has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Here we describe FTY720 (fingolimod), an immunosuppressive agent currently being explored in phase III studies in renal transplantation and multiple sclerosis patients, to mediate time- and dose-dependent cell death in primary MCL cells (6 patients) and MCL cell lines, Jeko and Mino. FTY720-induced apoptosis was associated with reactive oxygen species (ROS) generation, Bax up-regulation but not associated with caspase 3 activation in MCL. FTY720 treatment resulted in time-dependent down-modulation of Cyclin D1 and phospho Akt (p-Akt) protein level, two critical disease-relevant molecules in the pathogenesis of MCL. Consistent with the modulation of Cyclin D1, FTY720-induced cell cycle arrest with accumulation of cells in G0/G1 and G2/M phases of the cell cycle with concomitant decrease in S phase entry. Importantly, FTY720 treatment was also associated with a time-dependent phospho Erk (p-Erk) induction in Mino and Jeko cells. To determine the in vivo efficacy of FTY720, we developed a preclinical, in vivo xenograft model of human MCL where MCL cell lines (Jeko, Mino and SP53) were engrafted into severe combined immune deficient (SCID) mice. Cell dose titration trials identified 4 × 107 Mino or Jeko cells injected intravenously via tail vein to result in consistent engraftment and fatal tumor burden in all mice. All mice engrafted with 4 × 107 Jeko cells developed a disseminated disease within 3 weeks and had a median survival of 28 days (compared to 43 days for Mino and 51 days for SP53). Because the Jeko cell line was established from the peripheral blood of a patient with blastic variant MCL and demonstrated a more resistant phenotype to several immuno-chemoterapeutic compounds, this cell line was chosen to create a more stringent in vivo preclinical model. SCID mice were treated with the monoclonal antibody TMβ1 to deplete murine NK cells, engrafted with 4 × 107 Jeko cells and observed daily for signs of tumor burden. Ten mice/group were treated starting at day 15 post-engraftment with intraperitoneal injection of 100 μl of saline or FTY720 (5 mg/kg resuspended in 100 μl of saline), every day, for two weeks. The median survival for FTY720-treated mice (N=10) was 38 days (95% CI:30-39) compared to 26.5 days (95% CI: 26-27 days) for the control group mice (N=10). The results from the log-rank test indicated an overall statistical significant difference in survival functions between the FTY720 treatment and the control group (p=0.001). These results provide the first evidence for a potential use of FTY720 in targeting key pathways that are operable in the pathogenesis of MCL and warrant the further investigation of FTY720 in combination with other agents in clinical trials treating patients with MCL. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 91 (6) ◽  
pp. 672-685 ◽  
Author(s):  
M.M.O. Abdelaal ◽  
G.P. Brennan ◽  
A. Abdel-Aziz ◽  
I. Fairweather

AbstractAn in vivo study in the laboratory rat model has been carried out to monitor changes to the tegument and gut of adult Fasciola hepatica following treatment with myrrh (‘Mirazid’). Rats infected with the triclabendazole-resistant Dutch isolate were dosed orally with Mirazid at a concentration of 250 mg/kg and flukes recovered 2, 3 and 7 days post-treatment (pt). The flukes were processed for examination by scanning and transmission electron microscopy. A variety of changes to the external surface were observed, culminating in the sloughing of the tegumental syncytium. Internal changes to the syncytium and tegumental cell bodies were more severe and were evident from 2 days pt onwards. Swelling of the basal infolds (leading to flooding of the surface layer) and a decline in secretory body production were the major changes seen. The gastrodermal cells were less severely affected than the tegument, pointing to a trans-tegumental route of uptake for Mirazid by the fluke. Some loss of muscle fibres in the main somatic muscle layers was observed, which may be correlated with the decline in movement of flukes seen at recovery.


2013 ◽  
Vol 110 (4) ◽  
pp. 625-631 ◽  
Author(s):  
Virginie Alexandre ◽  
Patrick C. Even ◽  
Christiane Larue-Achagiotis ◽  
Jean-Marc Blouin ◽  
François Blachier ◽  
...  

Lactose malabsorption is associated with rapid production of high levels of osmotic compounds, such as organic acids and SCFA in the colon, suspected to contribute to the onset of lactose intolerance. Adult rats are lactase deficient and the present study was conducted to evaluatein vivothe metabolic consequences of acute lactose ingestion, including host–microbiota interactions. Rats received diets of 25 % sucrose (S25 control group) or 25 % lactose (L25 experimental group). SCFA and lactic acid were quantified in intestinal contents and portal blood. Expression of SCFA transporter genes was quantified in the colonic mucosa. Carbohydrate oxidation (Cox) and lipid oxidation (Lox) were computed by indirect calorimetry. Measurements were performed over a maximum of 13 h. Time, diet and time × diet variables had significant effects on SCFA concentration in the caecum (P< 0·001,P= 0·004 andP= 0·007, respectively) and the portal blood (P< 0·001,P= 0·04 andP< 0·001, respectively). Concomitantly, expression of sodium monocarboxylate significantly increased in the colonic mucosa of the L25 group (P= 0·003 att= 6 h andP< 0·05 att= 8 h). During 5 h after the meal, the L25 group's changes in metabolic parameters (Cox, Lox) were significantly lower than those of the S25 group (P= 0·02). However, after 5 h, L25 Cox became greater than S25 (P= 0·004). Thus, enhanced production and absorption of SCFA support the metabolic changes observed in calorimetry. These results underline the consequences of acute lactose malabsorption and measured compensations occurring in the host's metabolism, presumably through the microbiota fermentations and microbiota–host interactions.


Author(s):  
Amir Reza Karamibonari

Introdution: Crataegus oxycanta (hawthorn) is used in herbal and homeopathic medicine as a cardiotonic.The present study was done to investigate the effect of the Crataegus oxycanta on antioxidant status in induced myocardial infarction in rat. Methods: In this experimental study, four groups of wistar rats (200-220g) each comprising 10 animals, were selected for this study. Group I, rats served as control. Group II rats were given isoperternol (85mg/kg body weight) subcutaneously on 15th and 16th days. Group III rats were given Crataegus oxycanta (100mg/kg/day), orally for 30 days.  Group IV rats were given Crataegus oxycanta (100mg/kg/day), orally for 30 days and isoperternol (85mg/kg body weight, subcutaneously) was given on 15th and 16th days. At the end of the experimental period, the rats were anaesthetized and blood obtained from the heart then rats were sacrificed and the hearts were removed for biochemical and histological analysis. The activity of malondialdehyde (MDA), catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidants was studied. Descriptive one-way analysis of variance (ANOVA) was used in different group. Significance was defined as P ≤ 0.05. Statistical analysis was performed using SPSS software version 16. Results: Crataegus significantly reduced plasma and heart tissue MDA levels (p<0.05) and significantly increased catalase, SOD, GPX and total antioxidant levels versus the group that received only isoperternol (p<0.05 ). Crataegus also decreased the rate of edema, inflammatory cell infiltration and heart tissue necrosis compared to the group that received only isoperternol. Conclusion: The study confirms the protective effect of Crataegus oxycanta against tissue damage and  oxidative stress caused by  isoperternol induced myocardial infarction


2021 ◽  
Vol 30 (3) ◽  
pp. 182-90
Author(s):  
Neng Nenden Mulyaningsih ◽  
Ariadne Lakshmidevi Juwono ◽  
Djarwani Soeharso Soejoko ◽  
Dewi Apri Astuti

BACKGROUND New therapeutic options are often explored in in vivo studies using animals like rats. Since rats are small, it is difficult to examine them in a computed tomography (CT) scan. This study aimed to introduce a multi-hole spherical model CT scan method as a new, fast, economical, and reliable method to characterize large quantities of rat bones at once in estimating the timing of osteoporosis in ovariectomized white rats. METHODS 50 female white rats (12 weeks old) were treated as the control group, and 40 rats of the same age were ovariectomized to establish the osteoporosis model. Sham rats were sacrificed at 13, 15, 17, 19, and 21 weeks old, while the ovariectomized rats were sacrificed at 15, 17, 19, and 21 weeks old. Afterward, tibia bones were removed, placed in the multi-hole spherical model, and characterized using a CT scan. Their characteristics were compared using a scanning electron microscope (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). RESULTS The Hounsfield unit scores resulted from the multi-hole spherical model CT scan method of tibia bones of rats were consistent with the percentage of the osteocyte cavities, canalicular diameters, and crystal size. The multi-hole spherical model CT scan method could produce 50 times more data than the SEM, TEM, or XRD. CONCLUSIONS Multi-hole spherical model CT scan was considered good and reliable in assessing bone quality parameters in rat samples simultaneously.


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