scholarly journals Aspirin Protective Effect Against Cyclophosphamide Hematological Toxicity In Experimental Animals

2021 ◽  
Author(s):  
Imad Hashim ◽  
Zaid Al-Attar ◽  
Saba Hamdan
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Enzyme Inhibitors ◽  
Alkylating Agents ◽  
Inhibitory Effect ◽  
Cytotoxic Agents ◽  
Hematological Toxicity ◽  
Bone Marrow Toxicity ◽  
Weight Changes ◽  
Dose Dependent

Bone marrow toxicity is the most important factor limiting the use of cytotoxic drugs like alkylating agents in cancer treatment. Recently PG synthase enzyme inhibitors have been reported to potentiate the cytotoxic effects of these agents on cancer cells but little is known if they can affect the toxicity of these agents on bone marrow or other tissues. Cyclophosphamide is one of the most commonly used alkylating agent. In the present work, the effect of these PG synthase enzyme inhibitors, aspirin on cyclophosphamide myelotoxicity was determined employing the peripheral blood count to reflect bone marrow injury. The effect on body weight changes caused by cyclophosphamide was also determined. 1. Cyclophosphamide in doses of 25, 50 and 75 mg/kg i. v. produced as a dose dependent reduction in total WBC count, granulocyte, non granulocyte, and Hb% which was maximum on second day after injection and still present on 5th day post injection. It also produced a dose dependent reduction in body weight on day 5 after injection. 2. Aspirin in doges of 75, 150 and 300 mg/kg i. m. protected against the reduction in WBC counts 'measured for 5 days after injection of cyclophosphamide (50 mg/kg). This protection was not dose dependent, though it was more optimum with 300 mg/kg and disappeared largely when a dose of 450 mg/kg was used. Aspirin did not prevent the changes in Hb% but retard the reduction in body weight caused by cyclophosphamide. 3. It is concluded that aspirin can help to reduce injury and enhance recovery from bone marrow toxicity caused by cytotoxic agents such as the alkylating drugs cyclophosphamide for which no specific antidote is available. Aspirin produces this effect possibly by eliminating the harmful inhibitory effect of excess PGs or leukotrienes, released by bone marrow injury on growth factors of haemopoietic progenitor cells. The magnitude of this protection on WBC counts does not seem to differ between either PG synthase enzyme inhibitors or steroids when used alone or in combination although a synergistic effect in protecting erythropoiesis is observed.

scholarly journals Flow cytometric detection of erythropoietic cytotoxicity in mouse bone marrow.

1991 ◽  
Vol 39 (1) ◽  
pp. 15-21 ◽  
Author(s):  
V M Benning ◽  
M B Maratrat ◽  
E C Fournier ◽  
C P Melcion ◽  
A C Cordier
Keyword(s):  
Bone Marrow ◽  
Alkylating Agents ◽  
Flow Cytometric Analysis ◽  
Cytotoxic Agents ◽  
Mouse Bone Marrow ◽  
Dna And Rna ◽  
Flow Cytometric ◽  
Polychromatic Erythrocytes ◽  
Kinetics Of ◽  
Dose Dependent

Erythroblast proliferation and maturation in bone marrow are the processes leading to the formation of polychromatic erythrocytes (PE) and normochromatic erythrocytes (NE), respectively. PE contain RNA but no DNA, and can therefore be distinguished both from NE (which lack both RNA and DNA) and from nucleated cells (which contain both DNA and RNA). Cytotoxic agents that induce impairment of the maturation process change the PE:NE ratio. We have developed a simple and rapid method of determining the PE:NE ratio, based on flow cytometric analysis of formaldehyde-fixed, acridine orange (AO)-stained cells. The effects of cyclophosphamide (CP), mitomycin C (MMC), and vincristine (VC) were tested and the PE:NE ratio was evaluated over 7 days of treatment. In this study we monitored the kinetics of these compounds and were able to demonstrate both a time- and a dose-dependent effect. We detected a difference between the effects of the alkylating agents tested and those induced by the spindle inhibitor tested. Flow cytometry of fixed bone marrow samples stained with AO provides more information, better and more rapid statistical analysis, than conventional microscopic methods for counting the PE:NE ratio.

Phytochemical Screening and Anti-Diabetic Efficacy of O. Sanctum Seed Extract on Streptozotocin Induced Diabetic Rats

2017 ◽  
Vol 54 (3) ◽  
pp. 336
Author(s):  
Kavitha K. ◽  
Ponne S.
Keyword(s):  
Body Weight ◽  
Digestive Enzymes ◽  
Fasting Blood Glucose ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Seed Extract ◽  
Phytochemical Screening ◽  
Weight Changes

The present study was designed to assess the in vitro and in vivo anti-diabetic efficacy of <em>O. sanctum</em> seed and its phytochemical screening. In vitro inhibitory effect on carbohydrate digestive enzymes like α-amylase and α-glucosidase and in vivo parameters such as fasting blood glucose and body weight changes were studied, a potent inhibitory effect was observed on activities of digestive enzymes and a marked decrease in the glucose level in the <em>O. sanctum</em> seed extract treated streptozotocin induced diabetic rats was noted. Further a marked reduction in body weight was also observed.

scholarly journals O 6-Benzylguanine Potentiates the In Vivo Toxicity and Clastogenicity of Temozolomide and BCNU in Mouse Bone Marrow

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1566-1573 ◽  
Author(s):  
Nachimuthu Chinnasamy ◽  
Joseph A. Rafferty ◽  
Ian Hickson ◽  
John Ashby ◽  
Helen Tinwell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antitumor Agents ◽  
Alkylating Agents ◽  
Micronucleus Assay ◽  
Hematological Toxicity ◽  
Mouse Bone Marrow ◽  
Macrophage Colony ◽  
Lower Magnitude ◽  
Marrow Cellularity

Abstract The effects of treatment of mice with O6-benzylguanine (O6-BeG) on the levels of O6-alkylguanine-DNA alkyltransferase (ATase) in the hematopoietic compartment and on the in vivo sensitivity of hematopoietic progenitor cells to the toxic and clastogenic effects of the antitumor agents 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) and temozolomide were studied. When the overall effects of BCNU alone or with O6-BeG pretreatment were compared, dose potentiating factors of 4.17 for marrow cellularity, 4.57 for granulocyte macrophage-colony forming cells (GM-CFC) and 8.25 for colony forming unit-spleen (CFU-S) in O6-BeG pretreated versus nonpretreated animals were observed. A similar trend of dose potentiation was observed for temozolomide, although it was of lower magnitude: 1.20 for marrow cellularity, 1.63 for GM-CFC, and 1.68 for CFU-S. When the clastogenic effects of BCNU and temozolomide were examined in the mouse bone marrow micronucleus assay, a significantly (P < .05 to .001) higher frequency of micronuclei formation was observed in mice that received O6-BeG pretreatment compared with mice that received no pretreatment. These data suggest that the use of O6-BeG as a tumor-sensitizing agent before treatment of patients with O6-alkylating agents may lead to more severe hematological toxicity and possibly to an increased incidence of secondary leukemias as a result of elevated mutation frequencies in these patients.

Effect of protoporphyrin IX on ursodeoxycholate-induced hypercholeresis in the rat

1988 ◽  
Vol 75 (6) ◽  
pp. 593-599
Author(s):  
J. J. Garcia-Marin ◽  
J. G. Redondo-Torres ◽  
F. Perez-Barriocanal ◽  
M. M. Berenson
Keyword(s):  
Body Weight ◽  
Bile Acid ◽  
Bile Flow ◽  
Sodium Taurocholate ◽  
Protoporphyrin Ix ◽  
Inhibitory Effect ◽  
Bicarbonate Secretion ◽  
Bile Formation ◽  
Dose Dependent ◽  
Bile Acid Secretion

1. It is known that the perfusion of rat livers with solutions containing protoporphyrin IX induces a decrease in bile flow which is not due to inhibition of bile acid secretion but rather to decreased electrolyte transport into bile. By contrast, ursodeoxycholate induces hypercholeresis, partly due to a marked stimulation of biliary bicarbonate secretion. The aim of the present work was to investigate the effect of protoporphyrin IX on ursodeoxycholate-induced choleresis in anaesthetized male Wistar rats. 2. Protoporphyrin IX infusion at rates of 10, 20 and 40 μg min−1 100 g−1 body weight into the jugular vein induced a dose-dependent inhibitory effect on bile flow as well as on bile acid and electrolyte secretion. The lowest infused rate only induced slight and non-significant changes in spontaneous bile formation and functional variables such as glycaemia, packed cell volume, blood pH, Pco2, Po2 and bicarbonate concentration, and in hepatic carbonic anhydrase activity. It was thus considered as a subtoxic dose. 3. Sodium taurocholate was infused (0.5 μmol min−1 100 g−1 body weight) over the second hour of the lowest dose of protoporphyrin IX infusion. In these rats, no significant changes in bile flow or bile acid and electrolyte secretion were observed as compared with animals receiving sodium taurocholate plus saline solution. 4. Bile acid secretion induced by ursodeoxycholate infusion (1 μmol min−1 100 g−1 body weight) was similar both in rats receiving ursodeoxycholate plus saline solution and in animals infused with this bile acid over the second hour of the lowest dose of protoporphyrin IX infusion. However, bile flow and biliary bicarbonate secretion induced by ursodeoxycholate were markedly impaired (− 43% and − 56%, respectively) by protoporphyrin IX. 5. These results indicate that in the rat, in vivo, protoporphyrin IX impairs bile formation in a dose-dependent manner. They suggest that the mechanism(s) involved in ursodeoxycholate-induced bicarbonate secretion, and hence hypercholeresis, are particularly sensitive to the inhibitory effect of protoporphyrin IX.

Current Management of the Myeloproliferative Disorders: A Case-Based Review

2006 ◽  
Vol 130 (8) ◽  
pp. 1151-1156
Author(s):  
Lawrence Rice ◽  
Kelty R. Baker
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Polycythemia Vera ◽  
Marrow Transplantation ◽  
Alkylating Agents ◽  
Treatment Strategies ◽  
Antiplatelet Agents ◽  
Myeloproliferative Disorders ◽  
Cytotoxic Agents ◽  
Actual Case

Abstract Context.—Properly managed, the myeloproliferative disorders are generally compatible with prolonged survival. Challenges to the hematologist include knowing when and how best to intervene to prevent and manage complications. The cytoreductive agent of choice for these disorders is currently hydroxyurea, emerging from randomized trials beginning with those of the Polycythemia Vera Study Group. Objective.—To examine the roles and shortcomings of interventions (including hydroxyurea, antiplatelet agents, anagrelide, interferon, thalidomide, alkylating agents, cell cytopheresis, erythropoietins, splenectomy, bone marrow transplantation, and imatinib) for myeloproliferative disorders. Data Sources.—This report uses actual case histories to illustrate the roles and shortcomings of these interventions. Conclusions.—Beyond phlebotomy for polycythemia vera, patients with polycythemia vera and essential thrombocythemia can be stratified by their risk for thrombosis, which guides the institution of cytoreductive therapies. High-risk patients generally benefit from cytoreductive therapy, and hydroxyurea has emerged as the agent of choice, because alkylating agents (and P32) have high leukemogenic potentials. Anagrelide and interferon are second-line agents. The addition of low-dose aspirin is beneficial for most, helping to prevent arterial thrombotic complications. Therapy in any of these disorders should be tailored to the unique characteristics of the individual patient. With myelofibrosis, therapeutic options run the gamut from observation, erythropoietic stimulators, cytotoxic agents, splenectomy, and bone marrow transplantation. Thalidomide and imatinib have shown some utility. Future challenges are the refinement of individualized treatment strategies and the development of targeted therapies based on rapidly expanding understanding of the molecular perturbations in these disorders.

Donor Bone Marrow Derived IL-17 Expressing Cells Exacerbate Chronic Graft-Versus-Host Disease in a Murine Bone Marrow Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2345-2345
Author(s):  
Rie Kuroda ◽  
Ryosei Nishimura ◽  
Katsuaki Sato ◽  
Hideaki Maeba ◽  
Kazuhito Naka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Graft Versus Host Disease ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Clinical Symptoms ◽  
Chronic Gvhd ◽  
Weight Changes ◽  
Host Disease ◽  
Graft Versus Host

Abstract Th17 is a newly identified T cell lineage that secretes the proinflamatory cytokine IL-17. Th17 cells have been shown to play a crucial role in mediating autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), arthritis, and colitis. However, recent study showed that donor Th17 cell ameliorated acute graft-versus-host disease (GVHD) due to the downregulation of Th1 differentiation in a murine BMT model. The role of IL-17 on developing chronic GVHD, which is pathologically similar to autoimmue diseases, remains unanswered. To this end, we compared the development of chronic GVHD between the lethally irradiated mice (Balb/c, H-2d) given IL-17 knockout(IL- 17KO, C57BL/6 background, H-2b) bone marrow (BM) cells and wild type BM cells with low dose WT splenocytes to induce sublethal acute GVHD and chronic GVHD subsequently. Up to day 60 after BMT no significant differences in clinical symptoms of GVHD including body weight changes were observed between the mice co-injected with IL-17 KO BM cells plus WT splenocytes and WT BM cells plus WT splenocytes. After day 60 the mice receiving WT BM cells plus WT splenocytes experienced weight loss accompanied by skin inflammatory changes, while mice receiving IL-17KO BM plus WT splenocytes showed minimal signs of GVHD as well as mice receiving IL-17 KO BM or WT BM alone. Recovery of body weight on day 160 after BMT was statistically different between two groups (p=0.035). Taken together, IL-17 was exacerbation factor of chronic GVHD, but not acute GVHD. Next we further evaluated the percentage of Th17 cells derived from BM cells (not from infused splenocytes) in the spleen on day 160 after BMT. Percentages of IL-17 expressing cells in the mice receiving WT BM plus WT splenocytes in spleen were significantly higher than those of WT BM alone receiving mice in CD4 (p=0.03) subpopulations. In conclusion, Th17 cells critically involved in the pathogenesis of chronic GVHD. Neutralizing IL-17 would be potent strategy for preventing chronic GVHD. Figure Figure

Inhibitory Effect of Tetrandrine on Pulmonary Metastases in CT26 Colorectal Adenocarcinoma–Bearing BALB/c Mice

2004 ◽  
Vol 32 (06) ◽  
pp. 863-872 ◽  
Author(s):  
Kou-Hwa Chang ◽  
Hui-Fen Liao ◽  
Hen-Hong Chang ◽  
Yu-Yawn Chen ◽  
Ming-Chien Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Body Weight ◽  
Tumor Metastasis ◽  
Colorectal Adenocarcinoma ◽  
Pulmonary Metastases ◽  
Inhibitory Effect ◽  
Control Group ◽  
Dependent Manner ◽  
Untreated Control Group ◽  
Dose Dependent

Tumor metastasis is a major cause of mortality in cancer patients. The anti-metastatic effect of tetrandrine, an alkaloid isolated from Stephania tetrandrae S. Moore, was investigated in a pulmonary metastatic model of colorectal cancer-bearing mice. Tetrandrine decreased the viability of murine colorectal adenocarcinoma CT26 cells in a time- and dose-dependent manner. CT26 cells were injected into BALB/c mice via a tail vein to establish pulmonary metastases. After this, the mice were given intraperitoneal injections of tetrandrine (10 mg/kg/day), 5-fluorouracil (5-FU) at the same dose, or vehicle for 5 consecutive days. Mice treated with tetrandrine had 40.3% fewer metastases than vehicle-treated mice, and those treated with 5-FU had 36.9% fewer metastases than controls. Both tetrandrine- and 5-FU-treated mice survived longer than mice in the untreated control group. There was no acute toxicity or obvious changes in body weight in any of the mice. These results suggest that tetrandrine may be a useful anti-metastatic agent.

Effects of the antiprogestin RU486 on progesterone-dependent uterine development and bioassay of progestational activity in estrogen-primed immature female dogs

1988 ◽  
Vol 118 (3) ◽  
pp. 389-398 ◽  
Author(s):  
P. W. Concannon ◽  
L. Dillingham ◽  
I. M. Spitz
Keyword(s):  
Body Weight ◽  
Serum Cortisol ◽  
Uterine Weight ◽  
Weight Changes ◽  
Immature Female ◽  
Cortisol Levels ◽  
Oral Doses ◽  
Dose Dependent ◽  
Antagonist Ru486 ◽  
Uterine Development

Abstract. A bioassay for progesterone activity in dogs was established based on uterine weight (mg/kg body weight) in immature beagles administered progesterone for 10 days starting 9 days after priming with estradiol cypionate (50 μg/kg, im). Progesterone doses of 0, 0.17, 0.5, 1.5, 13.5 and 40.5 mg/kg per day, im, produced dose-dependent increases in the weights of uterine horns obtained after 5 or 10 days of treatment. The total uterine responses (horn removed at 5 days plus horn and fundus removed at 10 days) to those were (mean ± sem) 374 ± 33, 465 ± 97, 684 ± 68, 795 ± 96, 1005 ± 38, 1232 ± 15 mg/kg, respectively. Responses to the 13.5 mg/kg per day dose of progesterone in dogs given the steroid antagonist RU486 at daily oral doses of 5, 20 and 50 mg/kg were reduced to values of 634 ± 24, 464 ± 74 and 468 ± 18 mg/kg, respectively, vs 1005 ± 38 mg/kg in controls. Mean progesterone levels were 27 ± 1 μg/l. The RU486 did not produce any consistent alterations in serum cortisol levels. The results suggest that, in immature bitches, uterine weight changes can be used to bioassay progestin activity following estrogen priming, RU486 is more potent as an antiprogestin than as an antiglucocorticoid, and RU486 at oral doses of 5 and 20 mg/kg exerts submaximal and maximal antiprogestin activity, respectively, in the presence of physiological levels of progesterone.

scholarly journals O 6-Benzylguanine Potentiates the In Vivo Toxicity and Clastogenicity of Temozolomide and BCNU in Mouse Bone Marrow

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1566-1573
Author(s):  
Nachimuthu Chinnasamy ◽  
Joseph A. Rafferty ◽  
Ian Hickson ◽  
John Ashby ◽  
Helen Tinwell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antitumor Agents ◽  
Alkylating Agents ◽  
Micronucleus Assay ◽  
Hematological Toxicity ◽  
Mouse Bone Marrow ◽  
Macrophage Colony ◽  
Lower Magnitude ◽  
Marrow Cellularity

The effects of treatment of mice with O6-benzylguanine (O6-BeG) on the levels of O6-alkylguanine-DNA alkyltransferase (ATase) in the hematopoietic compartment and on the in vivo sensitivity of hematopoietic progenitor cells to the toxic and clastogenic effects of the antitumor agents 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) and temozolomide were studied. When the overall effects of BCNU alone or with O6-BeG pretreatment were compared, dose potentiating factors of 4.17 for marrow cellularity, 4.57 for granulocyte macrophage-colony forming cells (GM-CFC) and 8.25 for colony forming unit-spleen (CFU-S) in O6-BeG pretreated versus nonpretreated animals were observed. A similar trend of dose potentiation was observed for temozolomide, although it was of lower magnitude: 1.20 for marrow cellularity, 1.63 for GM-CFC, and 1.68 for CFU-S. When the clastogenic effects of BCNU and temozolomide were examined in the mouse bone marrow micronucleus assay, a significantly (P < .05 to .001) higher frequency of micronuclei formation was observed in mice that received O6-BeG pretreatment compared with mice that received no pretreatment. These data suggest that the use of O6-BeG as a tumor-sensitizing agent before treatment of patients with O6-alkylating agents may lead to more severe hematological toxicity and possibly to an increased incidence of secondary leukemias as a result of elevated mutation frequencies in these patients.

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