Alleviation of Simvastatin-Induced Myopathy in Rats by the Standardized Extract of Ginkgo Biloba (EGb761): Insights into the Mechanisms of Action

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.

2013 ◽  
Vol 1 (1) ◽  
pp. 112
Author(s):  
Monali R. Patel ◽  
Ramtej J. Verma

The aim of the present investigation was to evaluate the ameliorative effect of Eclipta alba extract against carbon tetrachloride (CCl4)–induced structural and functional changes in livers of mice. Healthy adult Swiss strain female albino mice were orally administered with CCl4 (826 mg/kg body weight/day, p.o.) alone and along with Eclipta alba extract (100, 200 and 300 mg/kg body weight/day, p.o.) for 30 days. The degree of protection was determined by measuring histopathological changes and lipid peroxidation in liver as well as activities of ALT, AST, ACP, ALP, LDH, γ-GT enzymes and bilirubin contents in serum of mice. The histopathological studies revealed severe necrosis, fatty infiltration, lymphocytic infiltration and fibrosis in liver of CCl4 treated mice. In addition, biochemical studies revealed a significant increase in lipid peroxidation. The enzymes activities as well as bilirubin contents in serum were significantly (p<0.05) increased in CCl4 only treated mice when compared with the control group. However, co-treatment of CCl4 along with Eclipta alba extract showed significant reductions in activities of enzymes and bilirubin content as compared with CCl4 alone treated mice. The effects were dose-dependent (r = 0.9826 to 1). Carbon tetrachloride induced lipid peroxidation was significantly (p<0.05) ameliorated in a dose-dependent manner. Histopathological changes were also ameliorated on treatment with Eclipta alba extract. The ameliorative effects of Eclipta alba on CCl4–induced hepatotoxicity could be due to its antioxidative property. The extract was found to be safe as evidenced by their high LD50.


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.


2008 ◽  
Vol 24 (9) ◽  
pp. 581-586 ◽  
Author(s):  
S Afshar ◽  
AA Farshid ◽  
R Heidari ◽  
M Ilkhanipour

The aim of this study was to investigate the dose-related effects of fenitrothion (FNT) on the liver and kidney. The study was conducted on 8-week-old male Wistar rats that were divided into four groups (three experimental groups and one control group) and were treated orally with different doses (25, 50, 100 mg/kg) of FNT for 28 consecutive days. After treatment, the rats were anesthetized with ether and liver and kidney samples were taken for histological studies. The results showed that the histopathological changes in the liver were mainly represented by parenchymatous degeneration of hepatocytes with mild necrosis, leukocytic infiltration in the portal area, severe congestion, and hemorrhage. These changes were dose dependent. Marked tubular dilation, hydropic degeneration in tubular epithelium, moderate congestion, and hemorrhage in the cortical and medulla part of the kidney were recorded. Histopathologic examination of the liver and kidney indicated a significant injury only in rats receiving 100 mg/kg FNT.


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.


1997 ◽  
Vol 273 (4) ◽  
pp. H1677-H1687 ◽  
Author(s):  
Zhi-Qing Zhao ◽  
James C. Todd ◽  
Hiroki Sato ◽  
Xin-Liang Ma ◽  
J. Vinten-Johansen

This study tests the hypothesis that cardioprotection exerted by adenosine A2-receptor activation and neutrophil-related events involves stimulation of ATP-sensitive potassium (KATP) channels on neutrophils during reperfusion. The adenosine A2 agonist CGS-21680 (CGS) inhibited superoxide radical generation from isolated rabbit polymorphonuclear neutrophils (PMNs) in a dose-dependent manner from 17.7 ± 2.1 to 7.4 ± 1.3 nmol/5 × 106 PMNs ( P < 0.05). Pinacidil, a KATP-channel opener, partially inhibited superoxide radical production, which was completely reversed by glibenclamide (Glib). Incremental doses of Glib in combination with CGS (1 μM) did not alter CGS-induced inhibition of superoxide radical generation. CGS significantly reduced PMN adherence to the endothelial surface of aortic segments in a dose-dependent manner from 189 ± 8 to 50 ± 6 PMNs/mm2( P < 0.05), which was also not altered by incremental doses of Glib. Infusion of CGS (0.025 mg/kg) before reperfusion reduced infarct size from 29 ± 2% in the Vehicle group to 15 ± 1% in rabbits undergoing 30 min of ischemia and 120 min of reperfusion ( P< 0.05). Glib (0.3 mg/kg) did not change the infarct size (28 ± 2%) vs. the Vehicle group and did not attenuate infarct size reduction by CGS (16 ± 1%). Glib did not change blood glucose levels. Cardiac myeloperoxidase activity was decreased in the ischemic tissue of the CGS group (0.15 ± 0.03 U/100 mg tissue) compared with the Vehicle group (0.37 ± 0.05 U/100 mg tissue; P < 0.05). We conclude that adenosine A2 activation before reperfusion partially reduces infarct size by inhibiting neutrophil activity and that this effect does not involve KATP-channel stimulation.


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.


2021 ◽  
Vol 33 (2) ◽  
pp. 129
Author(s):  
M. P. Thavhana ◽  
T. L. Nedambale ◽  
L. J. Shai ◽  
M. L. Mphaphathi

In poultry industry, chick viability is a crucial factor determining profitability from fertilized egg to placement at the farm. However, decreases in fertility and hatchability have been observed. Recently, there has been renewed interest in the use of silver nanoparticles (Ag-NPs) due to their antimicrobial properties and growth-promoting ability, and diamond nanoparticles (D-NPs) due to their biocompatibility properties. The aim of the study was to evaluate the effect of silver and diamond nanoparticles on chicken embryo oxidative status, biochemical indices, and expression of immune-related genes and on sperm cell viability. The experiment was conducted in Ross 308 chicken embryos and Ross 308 cockerels. One hundred and fifty fertilized eggs were divided randomly into 5 groups (5×30). Fertilized eggs were injected with 50 mg/L Ag-NPs at volumes of 100μL (group 1), 200μL (group 2) or 50 mg/L D-NPs at volumes of 100μL (group 3) or 200μL (group 4), or received no nanoparticles (control; group 5) and incubated at 37°C and 55% humidity for 20 days. Then, chicken blood was collected and centrifuged to evaluate alkaline phosphatase (ALP), alanine transaminase (ALT), lactate dehydrogenase (LDH), glucose, urea, and free haemoglobin. Chicken embryo liver was used to evaluate antioxidant capacity (TAC) and chicken embryo spleen was used to evaluate expression of the immune-related genes interleukin-1β (IL-1β), toll-like receptor (TLR)4, TLR2, and TLR15. Semen was randomly divided into 1 control and 8 treatment groups and treated with 50 mg/L Ag-NPs: group A (0.1ppm), group B (1ppm), group C (5ppm), group D (10ppm) or 50 mg/L D-NPs: group E (1ppm), group F (5ppm), group G (10ppm), and group H (20ppm). Sperm viability was analysed using prestoblue metabolic assay. Data were analysed using PROC in GLM procedure of SAS 2014 (SAS Institute Inc.). Decrease in sperm cell viability was recorded in a dose-dependent manner. Sperm cell viability decreased (P&lt;0.005) as the concentration of Ag-NP or D-NP increased. Addition of 100μL of Ag-NPs increased the growth rate of chicken embryo but not 200μL of Ag-NPs or addition of D-NPs. Increases in ALP, ALT, LDH, glucose and urea enzyme were observed in a dose-dependent manner in both Ag-NPs and D-NPs. Addition of 50 mg/L Ag-NPs or 50 mg/L D-NPs increased (P&lt;0.001) TAC of chicken embryo as the volume increased. Additions of 200μL of Ag-NPs, 100μL of D-NPs, and 200μL of D-NPs were haemolytic (P&lt;0.001) but addition of 100μL of Ag-NPs was not. Additions of 100 or 200μL of Ag-NPs or 100μL of D-NPs downregulated IL-1β and 200μL of D-NPs upregulated IL-1β compared with the untreated control group. Additions of 100 or 200μL of Ag-NPs or 200μL of D-NPs induced expression of TLR4 and TLR15. Furthermore, addition of Ag-NPs did not result in expression of TLR2. We concluded that administration of 50 mg/L Ag-NPs and 50 mg/L D-NPs in ovo improve immune status and administration of 100μL of Ag-NPs improved the growth rate of chicken embryo. However, toxicity associated with 50 mg/L Ag-NPs and 50 mg/L D-NPs remains a concern and need to be addressed before use.


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