scholarly journals Bentonite diminishes DON-induced changes in bone development in mink dams

2016 ◽  
Vol 60 (3) ◽  
pp. 349-355 ◽  
Author(s):  
Ewa Tomaszewska ◽  
Siemowit Muszyński ◽  
Piotr Dobrowolski ◽  
Krzysztof Kostro ◽  
Iwona Taszkun ◽  
...  

AbstractIntroduction: The aim of this study was to determine the effect of deoxynivalenol (DON), given alone or with bentonite (which eliminates mycotoxicity) in the diet of mink dams throughout mating, pregnancy, and lactation period to pelt harvesting, on the mechanical properties and geometry of their long bones.Material and Methods: The minks were randomly assigned into two groups: a control group (not supplemented with DON, n = 15) and a group fed naturally DON-contaminated wheat and divided into three sub-groups (each sub-group n = 15), depending on bentonite dose: 0 M – sub-group fed naturally DON-contaminated wheat at a concentration of 3.7 mg kg−1 alone; 2 M – sub-group fed naturally DON-contaminated wheat at a concentration of 3.7 mg kg−1 and bentonite at a concentration of 2 kg 1000 kg−1; 0.5 M – sub-group fed naturally DON-contaminated wheat at a concentration of 3.7 mg kg−1 and bentonite at a concentration of 0.5 kg 1000 kg−1.Results: The DON treatment reduced the length of the femur compared to the control group and reduced the bone weight dependently on the amount of bentonite supplementation. However, DON treatment reduced the MRWT and CI of the femur, irrespective of the bentonite supplementation, compared to the control. The total BTD and BMC decreased in all DON-treated groups (irrespective of the bentonite supplementation). Furthermore, the densitometric analysis showed that the main changes in BMD and BMC indicated bone loss in the proximal and distal parts of bone covering the trabecular bone; whereas when bentonite was given at the dose of 2 kg 1000 kg−1 an increase in the whole BMD and BMC was observed in the femoral midshaft.Conclusion: Analysis of the geometrical parameters seems to indicate that endosteal resorption was delayed after bentonite supplementation. The addition of bentonite diminished the DON action on bone homeostasis in the mink dams. Thus bentonite could prevent DON-induced bone loss in a dose-dependent manner.

2012 ◽  
Vol 36 (1) ◽  
pp. 75-84
Author(s):  
Areej B. Abass

The present study was aimed to evaluate neurotoxic effects of oseltamivir phosphate in lactating pups of orally dosed mice mothers during lactation. Twelve recently parturited female albino mice were divided equally into three groups, one control and two treated groups, each group consists of 4 dosed dams and 8 chosen pups .The nursing dams of T1 and T2 dosed daily orally with 1mg/kg and 5mg/kg,oseltamivir phosphate respectively representing the therapeutic dose and 5 fold dose of drug while control group dosed with distilled water. Lactating mice pups of all groups examined for the following parameters: First parameter was body weight changes and gain: In which T1group showed significant increase in mice pups body weight gain after 14 day of treatment in comparison with control group and T2. Second parameter was clinical symptoms observation /daily, all treatment groups that showed neurotoxic symptoms appeared from 1st dose and extended along the next few days of treatment to be gradually disappeared and completely lost within the last days of treatment in dose dependent manner.These neurotoxic symptoms were weakness, convulsions ,lay on back or side, extended body, incoordination ,extended limbs and limbs stiffness. Third parameter was gross and histopathological studies which demonstrate that the brain was the most affected organ beside extensive lesions in liver, kidney, stomach and small intestine of treated groups in dose dependent manner.In conclusion of this study revealed that Oseltamivir phosphate produce neurotoxic effect in mice pups through indirect administration by nursing mothers dosing during lactation period and the level of toxicity was in dose dependent manner.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 199
Author(s):  
Urara Tanaka ◽  
Shunichi Kajioka ◽  
Livia S. Finoti ◽  
Daniela B. Palioto ◽  
Denis F. Kinane ◽  
...  

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).


2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Guili Bao ◽  
Yinglong Zhang ◽  
Xiaoguang Yang

AbstractIn this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.


2010 ◽  
Vol 30 (7) ◽  
pp. 591-602 ◽  
Author(s):  
Abdul Basir ◽  
Ahrar Khan ◽  
Riaz Mustafa ◽  
Muhammad Zargham Khan ◽  
Farzana Rizvi ◽  
...  

The aim of this study was to investigate effects of lambda-cyhalothrin (LCT) on clinical, hematological, biochemical and pathological alterations in rabbits (Oryctolagus cuniculus). New Zealand white female rabbits (n = 24) of 4-5 months age having 997.92 ± 32.83 g weight were divided into four equal groups. Group A (control) received normal saline intraperitoneally (ip). Animals in groups B, C and D were treated with LCT 1.0, 4.0 and 8.0 mg/kg bw ip. Each group received seven consecutive doses at an interval of 48 hours. Blood and serum samples were collected at an interval of 96 hours. Blood analysis revealed a significant (p < 0.05) decrease in red blood cell and white blood cell counts, hemoglobin concentration and lymphocytes, while mean corpuscular hemoglobin concentration, mean corpuscular volume, neutrophils, monocytes and eosinophils were increased. Serum biochemical analysis revealed significant (p < 0.05) decrease in serum total proteins and serum albumin, while an increase was seen in serum alanine aminotransferase and aspartate aminotransferase activities compared with the control group. Serum globulin values varied non-significantly in all treatment groups as compared to control group. A dose-dependent increase in the incidence of micronucleated polychromatic erythrocyte was observed. All gross and histopathological lesions observed in LCT-treated rabbits were dose-dependent. Liver of the treated rabbits exhibited extensive perihepatitis, hyperplasia of bile duct, necrosis, hemorrhages and congestion. In lungs, there were hemorrhages, thickened alveolar walls, congestion, emphysema, collapsed alveoli and accumulation of extensive inflammatory cells. Kidneys were congested and hemorrhagic whereas renal parenchyma and stroma were normal. Microscopically, heart showed congestion of blood vessels and nuclear pyknosis, myodegeneration. It was concluded from the study that LCT produced toxicopathological alterations in rabbits in a dose-dependent manner. On the basis of the results, it can be suggested that overdosing of LCT be avoided while treating animals for ectoparasites.


2017 ◽  
Vol 61 (3) ◽  
pp. 357-362 ◽  
Author(s):  
Ewa Tomaszewska ◽  
Piotr Dobrowolski ◽  
Siemowit Muszyński ◽  
Krzysztof Kostro ◽  
Iwona Taszkun ◽  
...  

AbstractIntroduction: The aim of the study was to investigate the mechanical and geometric properties as well as bone tissue and mineral density of long bones in mink dams exposed to deoxynivalenol (DON) since one day after mating, throughout gestation (ca. 46 d) and lactation to pelt harvesting. Material and Methods: Thirty clinically healthy multiparous minks (Neovison vison) of the standard dark brown type were used. After the mating, the minks were randomly assigned into two equal groups: nontreated control group and DON group fed wheat contaminated naturally with DON at a concentration of 1.1 mg·kg-1of feed. Results: The final body weight and weight and length of the femur did not differ between the groups. However, DON contamination decreased mechanical endurance of the femur. Furthermore, DON reduced the mean relative wall thickness and vertical wall thickness of the femur, while vertical cortical index, midshaft volume, and cross-sectional moment of inertia increased. Finally, DON contamination did not alter bone tissue density, bone mineral density, or bone mineral content, but decreased the values of all investigated structural and material properties. Conclusion: DON at applied concentration probably intensified the process of endosteal resorption, which was the main reason for bone wall thinning and the weakening of the whole bone.


2022 ◽  
Vol 12 (3) ◽  
pp. 506-513
Author(s):  
Ying Lv ◽  
Liyan Ye ◽  
Xiujuan Zheng

This study aimed to explore the role of ATI-2341 in Asherman’s syndrome and its impact on menstrual blood-derived mesenchymal stem cells (MenSCs). Following establishment of endometrial injury model, MenSCs were extracted from rats and cultured. They were treated with ATI-2341 TFA at different concentrations (10 ng/mL, 50 ng/mL, 100 ng/mL) and MenSCs treated without ATI-2341 TFA were taken as controls. Flow cytometry was conducted to detect the cell cycle. MTT was carried out to evaluate proliferation of endometrial cells. The expression levels of MMP-9, TIMP-1, CK, and VIM were determined with staining used to reflect morphology of endometrium. Administration with ATI-2341 TFA resulted in decreased expression of MMP-9 and increased expression of TIMP-1 in a dose-dependent manner. Of note, the increase of ATI-2341 TFA concentration was accompanied with elevated cell proliferation rate, increased number of glands in the endometrium, and decreased fibrosis area. As treated with 100 ng/mL ATI-2341 TFA, the cells exhibited more glands than that under other concentrations with uniformly arranged glands and lowest expression levels of CK and VIM, control group had plenty of blue-stained collagen fibers in the intima and least amount of glands. ATI-2341 TFA 100 ng/mL induced endometrial epithelial recruitment effect on MenSCs and promoted endometrial repair more significantly than Gi-3 pathway agonists. Collectively, ATI-2341 TFA enhances MenSC recruitment and facilitates endometrial epithelial cells proliferation and the repair of uterine damage in Asherman’s syndrome through Gi pathway. These findings provide a\ novel insight into the MenSC-based treatment against Asherman’s syndrome and deserve further investigation.


Author(s):  
SAMBIT KUMAR SAHOO ◽  
STHITAPRAGNYA PANDA

Objective: The objective of the study was to evaluate the antinociceptive effect of Raphanus sativus Linn. using Randall Selitto method. Methods: Streptozotocin, lard, casein, cholesterol, DL-methionine, yeast powder, quercetin, thiobarbituric acid, 2-nitrobenzoic acid (5, 5, Dithiobis), hematoxylin, and hydrogen peroxide were used. A diet rich in fat content was fed to the animals for a period of 2 weeks. After a stabilization period of 2weeks, the treatment period started and continued for a period of 8weeks. The nociceptive parameters were assessed once a week by Randall Selitto method and hot plate test. After treatment, the animals were sacrificed, and antioxidant parameters were assessed using sciatic nerve homogenate and histopathological analysis of sciatic nerve. Results: Treatment R. sativus extract (RSE 100 mg/kg and 200 mg/kg) appreciably declined the levels of blood glucose in a dose-dependent manner, and it was comparable with standard quercetin. A significant increase in pain threshold levels was observed by the treatment RSE in hot plate method after the 4th week compared to diabetic control, and it was consistent until the end of treatment (p<0.01, p<0.001). In Randall Selitto method RSE produced a significant increase in paw withdrawal threshold after the 4th week compared to diabetic control, and it was consistently increased until the end of treatment. RSE (100 and 200 mg/kg) significantly restored the levels of antioxidant enzymes and decreased lipid peroxidation in a dose-dependent fashion in comparison with the diabetic control group. RSE (100 mg/kg and 200 mg/kg) attenuated the nerve degeneration and axonal swelling along with quercetin. Conclusion: The findings from the current study showed the antinociceptive and antioxidant effect of R. sativus in neuropathic pain in diabetes.


2019 ◽  
Vol 208 (3-4) ◽  
pp. 158-176
Author(s):  
Amany R. Mahmoud ◽  
Esam Omar Kamel ◽  
Marwa A. Ahmed ◽  
Esraa A. Ahmed ◽  
Tarek Hamdy Abd-Elhamid

Statins are the most widely prescribed cholesterol-lowering drugs to reduce the risk of cardiovascular diseases. Statin-induced myopathy is the major side effect of this class of drugs. Here, we studied whether standardized leaf extracts of ginkgo biloba (EGb761) would improve simvastatin (SIM)-induced muscle changes. Sixty Wistar rats were allotted into six groups: control group, vehicle group receiving 0.5% carboxymethyl cellulose (CMC) for 30 days, SIM group receiving 80 mg/kg/day SIM in 0.5% CMC orally for 30 days, SIM withdrawal group treated with SIM for 16 days and sacrificed 14 days later, and EGb761-100 and EGb761-200 groups posttreated with either 100 or 200 mg/kg/day EGb761 orally. Muscle performance on the rotarod, serum creatine kinase (CK), coenzyme Q10 (CoQ10), serum and muscle nitrite, muscle malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities were estimated. Additionally, muscle samples were processed for histopathological evaluation. We found that SIM decreased muscle performance on the rotarod, serum CoQ10, as well as muscle SOD and CAT activities while it increased serum CK, serum and muscle nitrite, as well as muscle MDA levels. SIM also induced sarcoplasmic vacuolation, splitting of myofibers, disorganization of sarcomeres, and disintegration of myofilaments. In contrast, posttreatment with EGb761 increased muscle performance, serum CoQ10, as well as muscle SOD and CAT activities while it reduced serum CK as well as serum and muscle nitrite levels in a dose-dependent manner. Additionally, EGb761 reversed SIM-induced histopathological changes with better results obtained by its higher dose. Interestingly, SIM withdrawal increased muscle performance on the rotarod, reduce serum CK and CoQ10, and reduced serum and muscle nitrite while it reversed SIM-induced histopathological changes. However, SIM withdrawal was not effective enough to restore their normal values. Additionally, SIM withdrawal did not improve SIM-induce muscle MDA, SOD, or CAT activities during the period studied. Our results suggest that EGb761 posttreatment reversed SIM-induces muscle changes possibly through its antioxidant effects, elevation of CoQ10 levels, and antagonizing mitochondrial damage.


2009 ◽  
Vol 610-613 ◽  
pp. 1364-1369 ◽  
Author(s):  
Zheng Li Xu ◽  
Jiao Sun ◽  
Chang Sheng Liu ◽  
Jie Wei

Nano-HAP (10-20nm) were obtained from East China University of Science and Technology. The osteoblasts were primary cultured from rat calvaria and then treated with five different concentrations(20,40,60,80,100µg/ml) of nano-HAP, the osteoblasts without nano-HAP was used as control group. Inhibition ratio, apoptotic rate were evaluated by MTT assay and flow cytometry (FCM), respectively. The specific surface area of nano-HAP was detected by BET. All date were expressed as mean ± standard deviation.Statistical analysis was performed by t test using software SPSS11.0 for Windows. The results indicated that the nano-HAP could inhibit the growth of osteoblasts in a dose-dependent manner. When the concentrations of nano-HAP were 20, 40, 60, 80, 100µg/ml, the inhibition ratio were 2.8%, 22.2%, 26.9%, 38% and 47.7%, and the apoptotic rate were 4.63%, 6.75%, 9.47%, 11.49%, 17.22%, respectively, which were obviously higher than that of control group. The nano-HAP significantly induced apoptosis in osteoblasts. There were the same tendency that the apoptotic and inhibition ratio of osteoblasts were rising with the increasing of the concentration of the nano-HAP. The specific surface area of nano-HAP was 148.140m2/g.


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