201 LIVER AND KIDNEY FUNCTION IN BOVINE FETUSES FROM EMBRYOS PRODUCED IN VIVO OR IN VITRO

2008 ◽  
Vol 20 (1) ◽  
pp. 180
Author(s):  
P. W. Farin ◽  
D. E. Malarkey ◽  
J. E. Alexander ◽  
C. E. Farin

Abnormal offspring syndrome can occur in fetuses and calves resulting from embryos produced in vitro or by nuclear transfer procedures. This study was conducted to determine the effects of in vitro embryo culture on fetal biochemistry profiles and histology of the liver and kidneys during late gestation. Embryos were produced in vivo by using superovulated cows (In Vivo) or in vitro by using a serum-containing culture system (In Vitro) as previously described (Miles et al. 2004 Biol. Reprod. 71, 1919–1926). Single blastocysts from each embryo production system were transferred nonsurgically into heifers. On Day 222 of gestation, fetuses from the In Vivo group (n = 12) and the In Vitro group (n = 12) were recovered in utero. Samples of fetal serum were collected for biochemical analysis. Samples of liver and kidney were prepared for histological evaluation. Stereological methods were used to determine the volume density of hepatocytes as well as kidney glomeruli and kidney tubules. Fetuses from the In Vitro group were heavier (P = 0.03) than those from the InVivo group (17.3 � 1.0 kg and 20.7 � 1.0 kg for InVivo and InVitro, respectively; least squares means � SEM). Liver and paired kidney weights per kilogram of body weight did not differ (P ≥ 0.10) with treatment (26.4 � 0.6 g kg–1 v. 27.6 � 0.6 g kg–1 and 7.8 � 0.5 g kg–1 v. 9.1 � 0.5 g kg–1 for liver and kidney, respectively). In addition, there was no effect of treatment on the volume densities of hepatocytes, kidney glomeruli, and kidney tubules. However, compared with the In Vivo group, fetuses from the In Vitro group had increased (P ≤ 0.02) concentrations of blood urea nitrogen (BUN; 13.8 � 1.8 mg dL–1 v. 19.8 � 1.8 mg dL–1) and BUN:creatinine ratio (4.6 � 0.8 v. 7.9 � 0.8). No differences were observed between the In Vivo and In Vitro groups for serum levels of creatinine, total bilirubin, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, glucose, insulin, and insulin-like growth factor-I. In summary, compared with bovine fetuses from in vivo-produced embryos, fetuses from in vitro-produced embryos had increased body weight, normal liver and kidney morphology, and increased concentrations of BUN during late gestation. Supported by the State of North Carolina.

1987 ◽  
Vol 65 (5) ◽  
pp. 1201-1205 ◽  
Author(s):  
Bodil Korsgaard

The ability of yolk-sac embryos of the blenny Zoarces viviparus (L.) to assimilate and metabolize exogenous glucose was investigated by in vivo and in vitro experiments. The investigations in vivo (experiment I) were performed by simultaneously injecting 14C-labelled glucose (30 μL (5 μCi)/100 g body weight) and unlabelled carrier glucose (100 mg/100 g body weight) into the ovary (loaded group). Controls received only 14C-labelled glucose (nonloaded group). The shape of the disappearance curve for the tracer glucose in the glucose-loaded group was similar to that for carrier glucose, with a gradual decrease during the first 9 h postinjection. Half-lives were calculated to be 5.17 h for tracer glucose and 5.41 h for carrier glucose in the loaded group. Both tracer and carrier glucose levels returned to control levels after 24 h in the loaded group. Accumulation of tracer glucose was significantly higher in yolk-sac embryos from the nonloaded control group compared with embryos from the loaded group. Tracer accumulation in maternal liver and kidney was low and showed an opposite pattern to accumulation in the embryos, with more tracer accumulated in the maternal liver and kidney from the loaded group compared with controls. After intraovarian preincubation with [14C]glucose, release of 14CO2 and DO14C (dissolved organic carbon) from assimilated tracers in the embryos in vitro was low. In another experiment (experiment II) the embryos were dissected out of the ovary of untreated females and incubated in vitro with [14C]glucose. The embryos assimilated the labelled glucose, and uptake rates were correlated with the ambient concentration of carrier glucose. Release from embryos into the medium of 14CO2 and DO14C from assimilated tracer glucose was at the same low level as after intraovarian preincubation with [14C]glucose in experiment I. In combination, the results show that as early as their yolk-sac period, embryos from Zoarces viviparus have the capacity for assimilating and metabolizing glucose from naturally occurring concentrations in the ovarian fluid in vivo or from media in vitro.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
J. O. Adebayo ◽  
E. A. Balogun ◽  
S. O. Malomo ◽  
A. O. Soladoye ◽  
L. A. Olatunji ◽  
...  

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties ofCocos nuciferawere evaluatedin vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25–500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active againstPlasmodium falciparumW2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was activein vivoagainstPlasmodium bergheiNK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P>0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P<0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.


Marine Drugs ◽  
2020 ◽  
Vol 18 (8) ◽  
pp. 428
Author(s):  
Fu-juan Jia ◽  
Zhuo Han ◽  
Jia-hui Ma ◽  
Shi-qing Jiang ◽  
Xing-ming Zhao ◽  
...  

The high toxicity of actinomycin D (Act D) severely limits its use as a first-line chemotherapeutic agent in the clinic. Actinomycin V (Act V), an analog of Act D, exhibited strong anticancer activity in our previous studies. Here, we provide evidence that Act V has less hepatorenal toxicity than Act D in vitro and in vivo, associated with the reactive oxygen species (ROS) pathway. Compared to Act D, Act V exhibited considerably stronger sensitivity for cancer cells and less toxicity to human normal liver LO-2 and human embryonic kidney 293T cells using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Notably, Act V caused less damage to both the liver and kidney than Act D in vivo, indicated by organ to body weight ratios, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (Scr) levels. Further experiments showed that the ROS pathway is involved in Act V-induced hepatorenal toxicity. Act V generates ROS and accumulates malondialdehyde (MDA), reducing levels of superoxide dismutase (SOD) and glutathione (GSH) in LO-2 and 293T cells. These findings indicate that Act V induces less hepatorenal toxicity than Act D in vitro and in vivo and merits further development as a potential therapeutic agent for the treatment of cancer.


Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.


2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nilutpal Sharma Bora ◽  
Partha Sarathi Bairy ◽  
Abdus Salam ◽  
Bibhuti Bhusan Kakoti

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.


2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Ross W. Stephens ◽  
Gregory D. Tredwell ◽  
Jessica L. Bell ◽  
Karen J. Knox ◽  
Lee A. Philip ◽  
...  

Abstract Background Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable 67Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs. Results Radiolabelling of polymer microspheres with 67Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent. Final in vitro binding yields after autoclaving averaged 94.7%. In vivo stability of the composite was demonstrated in New Zealand white rabbits by intravenous administration, and intrahepatic artery instillations were made in normal and VX2 tumour implanted rabbit livers. Stability of radiolabel was sufficient for rabbit lung and liver imaging over at least 3 hours and 1 hour respectively, with lung retention of radiolabel over 91%, and retention in both normal and VX2 implanted livers of over 95%. SPECT-CT imaging of anaesthetised animals and planar imaging of excised livers showed visible accumulation of radiolabel in tumours. Importantly, microsphere administration and complete liver dispersal was more easily achieved with 8 μm diameter MS than with 30 μm MS, and the smaller microspheres provided more distinct and localised tumour imaging. Conclusion This method of producing 67Ga-radiolabelled polymer microspheres is suitable for SPECT-CT imaging of the regional vascular delivery of microspheres to tumour sites in animal models. Sharper distinction of model tumours from normal liver was obtained with smaller MS, and tumour resolution may be further improved by the use of 68Ga instead of 67Ga, to enable PET imaging.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.


2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jianru Pan ◽  
Huocong He ◽  
Ying Su ◽  
Guangjin Zheng ◽  
Junxin Wu ◽  
...  

GST-TAT-SOD was the fusion of superoxide dismutase (SOD), cell-permeable peptide TAT, and glutathione-S-transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST-TAT-SOD against whole-body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST-TAT-SOD (2 kU/ml) 2 h before the 6 Gy whole-body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen. Moreover, the thymus index, hepatic antioxidant activity, and white blood cell (WBC) count of peripheral blood in irradiated mice pretreated with GST-TAT-SOD also remarkably increased. Although the treated and untreated irradiated mice showed no significant difference in the growth rate of animal body weight at 7 days postirradiation, the highest growth rate of body weight was observed in the GST-TAT-SOD-pretreated group. Furthermore, GST-TAT-SOD pretreatment increased resistance against 8 Gy whole-body irradiation and enhanced 30 d survival. The overall effect of GST-TAT-SOD seemed to be a bit more powerful than that of amifostine. In conclusion, GST-TAT-SOD would be a safe and potentially promising radioprotector.


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