scholarly journals Simvastatin-induced changes in the leukocytic system of porcine bone marrow

2018 ◽  
Vol 62 (3) ◽  
pp. 329-333 ◽  
Author(s):  
Anna Snarska ◽  
Dominika Wysocka ◽  
Liliana Rytel ◽  
Sławomir Gonkowski ◽  
Hanna Pawelec ◽  
...  

AbstractIntroductionSimvastatin is a substance which is commonly used as a medicine to reduce cholesterol level. Unfortunately, it shows numerous side effects. Simvastatin affects various internal organs, and among other detriments to health may cause persistent muscle weakness, osteolytic processes, headaches, and rashes. Until now knowledge of the influence of simvastatin on bone marrow cells has been rather scant and fragmentary.Material and MethodsDuring this experiment the numbers of all types of cells in the leukocytic system of porcine bone marrow were evaluated after 28 and 56 days of oral administration of simvastatin at a dose of 40 mg/day/animal.ResultsSimvastatin caused an increase in the number of all types of cells in the leukocytic system, and the most visible fluctuations concerned promyelocytes.ConclusionObservations obtained during the present study indicated that the results of the action of simvastatin on porcine bone marrow differ from those observed in other mammal species, including human. This may be due to various metabolic pathways within the bone marrow in the particular species, but the exact mechanisms of these actions are unknown at the present time.

2011 ◽  
Vol 108 (6) ◽  
pp. 1059-1068 ◽  
Author(s):  
Gamal Ramadan ◽  
Nadia M. El-Beih ◽  
Mai M. Zahra

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs that show a high therapeutic index, despite the widespread side effects and toxicity particularly in high-dose regimens and long-term use. Here, we evaluated and compared the efficacy of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) in alleviating the genotoxicity, immunosuppression and other complications induced by CP in non-tumour-bearing albino rats. The present study showed (probably for the first time) that both MLP and MLE significantly alleviated (P < 0·05–0·001) most side effects and toxicity of CP-treated rats including the increase in chromosomal aberrations of bone marrow cells and serum malondialdehyde level, the decrease in the level of serum Ig, the delayed type of hypersensitivity response as also the weights and cellularity of lymphoid organs, and myelosuppression, leucopenia, macrocytic normochromic anaemia as well as thrombocytopenia by reactivating the non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant system and increasing the mitotic index of bone marrow cells. The modulatory effects of marjoram leaves shown in the present study were dose dependent in most cases and much higher in MLE (21–23 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, sweet marjoram leaves (especially in the form of a herbal tea) may be useful as an immunostimulant and in reducing genotoxicity in patients under chemotherapeutic interventions.


2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Xian-Zhe Dong ◽  
Yu-Ning Wang ◽  
Xiao Tan ◽  
Ping Liu ◽  
Dai-Hong Guo ◽  
...  

This study aims at investigating the radioprotective effect of ethanol extract from Ji-Xue-Teng (JXT,Spatholobus suberectus) on radiation-induced hematopoietic alteration and oxidative stress in the liver. Mice were exposed to a single acuteγ-radiation for the whole body at the dose of 6.0 Gy, then subjected to administration of amifostine (45 mg/kg) or JXT (40 g crude drug/kg) once a day for 28 consecutive days, respectively. Bone marrow cells and hemogram including white cells, red cells, platelet counts, and hemoglobin level were examined. The protein expression levels of pJAK2/JAK2, pSTAT5a/STAT5a, pSTAT5b/STAT5b, and Bcl-2 in bone marrow tissue; levels of reactive oxygen species (ROS); and the activity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum and liver tissue were determined. At the end of the experiment, the effect of JXT on cell viability and G-CSF and G-CSFR levels in NFS-60 cells were tested by CCK-8 assay, ELISA, and flow cytometry. The results showed that the mice exposed toγ-radiation alone exhibited a typical hematopoietic syndrome. In contrast, at the end of the 28-day experiment, irradiated mice subjected to oral administration of JXT showed an obvious improvement on blood profile with reduced leucopenia, thrombocytopenia (platelet counts), RBC, and hemoglobin levels, as well as bone marrow cells. The expression of pJAK2/JAK2, pSTAT5a/STAT5a, and Bcl-2 in bone marrow tissue was increased after JXT treatment. The elevation of ROS was due to radiation-induced toxicity, but JXT significantly reduced the ROS level in serum and liver tissue, elevated endogenous SOD and GSH-PX levels, and reduced the MDA level in the liver. JXT could also increase cell viability and G-CSFR level in NFS-60 cells, which was similar to exogenous G-CSF. Our findings suggested that oral administration of JXT effectively facilitated the recovery of hematopoietic bone marrow damage and oxidative stress of the mice induced byγ-radiation.


2019 ◽  
Vol 21 (1) ◽  
pp. 164 ◽  
Author(s):  
Thomas Cluzeau ◽  
Nathan Furstoss ◽  
Coline Savy ◽  
Wejdane El Manaa ◽  
Marwa Zerhouni ◽  
...  

Myelodysplastic syndrome (MDS) defines a group of heterogeneous hematologic malignancies that often progresses to acute myeloid leukemia (AML). The leading treatment for high-risk MDS patients is azacitidine (Aza, Vidaza®), but a significant proportion of patients are refractory and all patients eventually relapse after an undefined time period. Therefore, new therapies for MDS are urgently needed. We present here evidence that acadesine (Aca, Acadra®), a nucleoside analog exerts potent anti-leukemic effects in both Aza-sensitive (OCI-M2S) and resistant (OCI-M2R) MDS/AML cell lines in vitro. Aca also exerts potent anti-leukemic effect on bone marrow cells from MDS/AML patients ex-vivo. The effect of Aca on MDS/AML cell line proliferation does not rely on apoptosis induction. It is also noteworthy that Aca is efficient to kill MDS cells in a co-culture model with human medullary stromal cell lines, that mimics better the interaction occurring in the bone marrow. These initial findings led us to initiate a phase I/II clinical trial using Acadra® in 12 Aza refractory MDS/AML patients. Despite a very good response in one out 4 patients, we stopped this trial because the highest Aca dose (210 mg/kg) caused serious renal side effects in several patients. In conclusion, the side effects of high Aca doses preclude its use in patients with strong comorbidities.


2003 ◽  
Vol 228 (6) ◽  
pp. 759-766 ◽  
Author(s):  
Mirim Jin ◽  
Hyang Jeon ◽  
Hyung Jin Jung ◽  
Bongcheol Kim ◽  
Sung Seup Shin ◽  
...  

PG101 is a water-soluble extract from Lentinus lepideus. It is a potential biological response modifier that activates selective cytokines in vitro, mainly by controlling cellular transcription factor NF-κB. Effects of PG101 were tested on bone marrow cells in irradiated mice. Mice were irradiated with a dose of 6 Gy and were given PG101 by gavages daily for 24 days. In PG101-treated mice, the number of colony-forming cells, including colony-forming units (CFU)-granulocytes/macrophages (GM) and erythroid burst-forming units (BFU-E), were increased to almost the levels seen in nonirradiated control as early as 8 days after irradiation. Two-color flow cytometric analysis using antibodies to ER-MP12 and ER-MP20 suggested that in the bone marrow cell population, PG101 increased the number of granulocytes (ER-MP12-20med) and myeloid progenitors (ER-MP12+20+). Analysis of surface c-Kit and Gr-1 proteins in bone marrow cells indicated that PG101 might induce differentiation of progenitor cells to granulocytes and/or proliferation of the committed cells. Lastly, oral administration of PG101 highly increased serum levels of GM-CSF, IL-6, and IL-1β. Interestingly, the level of TNF-α was elevated by irradiation in control mice, but was maintained at the background level in PG101-treated mice, suggesting that PG101 might effectively suppress TNF-α-related pathologic conditions. Our results strongly suggest the great potential of PG101 as an immune enhancer during radiotherapy and/or chemotherapy.


1980 ◽  
Vol 1 (6) ◽  
pp. 317-320 ◽  
Author(s):  
J.M. Rojo ◽  
Maria Pilar Portoles

2007 ◽  
Vol 4 (3) ◽  
pp. 343-350 ◽  
Author(s):  
Meenal Kumar ◽  
Ravindra Samarth ◽  
Madhu Kumar ◽  
Senthamil R. Selvan ◽  
Begraj Saharan ◽  
...  

Extract ofAdhatoda vasica(L) Nees leaves has been used for treatment of various diseases and disorders in Ayurved and Unani medicine. Modulatory effect of ethanolic extract ofA. vasica(L) Nees against radiation-induced changes in terms of histological alterations in testis, reduced glutathione (GSH), lipid peroxidation (LPO), acid and alkaline phosphatases levels, and chromosomal alterations in Swiss albino mice was studied at various post-irradiation intervals between 1 and 30 days. Mice exposed to 8 Gy radiation showed radiation-induced sickness including marked changes in histology of testis and chromosomal aberrations in bone marrow cells with 100% mortality within 22 days. When ethanolic leaf extract ofA. vasicawas given orally at a dose of 800 mg kg−1body weight per mouse for 15 consecutive days and then exposed to radiation, death ofAdhatoda-pretreated irradiated mice was reduced to 70% at 30 days. The radiation dose reduction factor was 1.43. There was significantly lesser degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and Leydig cells. Correspondingly, a significant decrease in the LPO and an increase in the GSH levels were observed in testis and liver ofAdhatoda-pretreated irradiated mice. Similarly, a significant decrease in level of acid phosphatase and increase in level of alkaline phosphatase were observed.Adhatodapretreatment significantly prevented radiation-induced chromosomal damage in bone marrow cells. The study suggests thatAdhatodaplant extract has significant radioprotective effects on testis that warrants further mechanistic studies aimed at identifying the role of major ingredients in the extract.


Author(s):  
Shireen Shaffu ◽  
James Taylor

The musculoskeletal system consists of specialized connective tissue whose primary function is to allow locomotion. The tissues of the musculoskeletal system are bones, muscles, tendons, and ligaments. In particular, the bony skeleton also has the task of protecting vital internal organs, contains the bone marrow, and is an intrinsic part of the metabolic pathways involved in calcium homeostasis. Motion is allowed by specialized articulating structures, the joints.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christiana M Schannwell ◽  
Muhammad Yousef ◽  
Carmen M Basalyk ◽  
Tobias Zeus ◽  
Michael Brehm ◽  
...  

Heart failure is a dangerous disease with an increasing frequency. Although conventional drug therapy may delay remodeling, there is no basic therapeutic regime available for preventing or even reversing this process. Several preclinical as well as clinical trials have shown that transplantation of autologous bone marrow cells improved cardiac function after myocardial infarction and chronic heart disease (CAD). We investigated the effects of intracoronary (ic) autologous stem cell transplantation (STX) at patients with non-ischemic dilated cardiomyopathy (DCM). Methods: A total of 10 patients with DCM were included in this study (group I). The control group also consists of 10 age and sex-matched patients with comparable ejection fraction (group II). CAD and myocarditis were excluded. All patients of group I received an ic autologous STX with mononuclear cells. Cell transplantation was performed via the ic administration route. All cells were infused directly into the dominant coronary vessel. To achieve a maximal ischemic stimulus all patients received Dobutamine intravenously and Dipipyridamol by ic application. All 20 patients were re-investigated after 3 months. Results: Three months after ic STX, the global left ventricular ejection fraction increased in patients from 18 ± 1 up to 26 ± 3% (p < 0.01). In parallel the physical ability (functional capacity) rose from 25 to 75 watt (p < 0.01). In addition, we found an improvement of maximum oxygen uptake under stress from 1236 ± 217 up to 1473 ± 198 ml/min (p < 0.01). Furthermore we documented a reduction of arrythmia. An unchanged or even impaired left ventricular function was not observed in any patient of group I. In the control group (group II) no significant changes were documented. No side effects of ic autologous STX were found, particularly no arrythmias, no heart insufficiency, no dyspnoea and no palpitations. Conclusion: These results show that transplantation of autologous bone marrow cells, as well as the ic approach, represents a novel and effective therapeutic procedure for the therapy of DCM. For this method of therapy, no ethical problems exist, and no side effects were observed. However, further experimental studies and controlled prospective clinical trials have to follow.


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