Toxic Effects Of Cyclophosphamide Research Articles

The antiapoptotic effects of conditioned medium from bone marrow-derived mesenchymal stromal stem cells on cyclophosphamide-induced testicular damage in rat: An experimental study.

Cyclophosphamide (CP) has some negative effects on the reproductive system. Stem cells and their metabolites are being utilized to enhance fertility after chemotherapy. This study aimed to investigate the impact of conditioned medium (CM) derived from bone marrow mesenchymal stromal stem cells (BM-MSCs) on the toxic effects of CP on testicles. BM-MSCs were isolated, a CM was collected and 25-fold concentrated. 24 male Wistar rats (8 wk, 200-250 gr) were randomly divided into following groups: control, CP, CP+ Dulbecco's Modified Eagle Medium (DMEM), CP+CM. CP was given at a single dose of 100 mg/kg. 2 wk after the CP administration, CM was injected into the testicular efferent duct. Sperm parameters, testicular histopathology, and the level of testosterone were analyzed 2 months after treatment. The expression of B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) genes were evaluated by real-time polymerase chain reaction. CP had a negative effect on testis histology (p 0.001) and sperm quality (p 0.001). It changed the expression of genes associated with apoptosis (p 0.001). Treatment with CM reduced the expression of Bax (p 0.001), while significantly increasing the expression of Bcl2 (p = 0.01). It improved sperm count (p = 0.03), viability (p 0.001), motility (p 0.001), spermatogonial count (p 0.001), and epithelial thickness of testicular tubules (p = 0.02). These findings suggest that CM produced from BM-MSCs may be valuable for therapeutic approaches in reproductive medicine and may lessen the side effects of CP.

Post-Transplant Cyclophosphamide for the Prevention of Graft-vs.-Host Disease in Allogeneic Hematopoietic Cell Transplantation: A Guide to Management for the Advanced Practitioner.

Cyclophosphamide remains a critical component to haploidentical transplant conditioning regimens. Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical bone marrow transplant setting. The relative ease of administration compared with ex vivo manipulations and efficacy in reducing GVHD has led to increasing PTCy use in transplant centers around the world. The role of PTCy has expanded to haploidentical transplantation with myeloablative conditioning regimens and peripheral blood progenitor cells as the donor source. Moreover, encouraging results in GVHD management have been shown with the use of PTCy alone or in combination with other immunosuppressives in the human leukocyte antigen-matched donor setting. The toxicity profile of cyclophosphamide varies extensively depending on dose, duration, overall drug exposure, and, potentially, pharmacogenetics. This review highlights the pharmacology, pharmacokinetics, and toxic effects of cyclophosphamide and offers practical guidance for clinical application in the post-transplant setting. We summarize data on the management of high-dose cyclophosphamide toxicities and provide insights into the pharmacogenetic implications on drug efficacy and safety data.

Toxic effects of Cyclophosphamide on Hepatic and Kidney tissues in Albino Mice Model

cyclophosphamide (CPA) is anti-tumor drug and is used for chemotherapy. CPA is a poisonous medication that hits both tumor and healthy cells in the body. The active ingredient is inactive in vitro and is replaced by metabolites, the most important of which is phosphoramide mustard. The goal of this study was to see how cyclophosphamide affects the histology of the liver and kidney tissues in mice animal model, as well as how it affects their biochemical functions. Twenty adult male Albino mice were randomly assigned to control and CPA treated group. CPA was given to the mice at dose of 200mg per kg body weight. After (25) days of treatment, mice were sacrificed. Hematoxylin and Eosin stains (H and E) were used to test the toxic effects of CPA on the liver and kidney histology. Our data showed the harmful effects of CPA drugs in the liver and kidney tissues, pathological changes were ranging from slight infiltration to sever necrosis and finally cytolysis also was observed. CPA-treated mice showed a significant (P<0.01) increased in serum creatinine, urea, and urea nitrogen levels. CPA-treated mice showed a tubular necrosis and inflammatory cell infiltration, as well as nephrotic changes when compared to control. CPA treatment demonstrated a significant (P<0.01) increased in Alanine Amino-Transferase (ALT), Aspartate Amino-Transferase (AST), Albumin and Bilirubin levels. Furthermore, livers of CPA-treated mice exhibited hepatocyte necrosis around central veins. Our data revealed the damaging and toxic effects of CPA against liver, kidney tissues and their biochemical functions.

Development and biological evaluation of protective effect of kidney targeted N-acetylated chitosan nanoparticles containing thymoquinone for the treatment of DNA damage in cyclophosphamide-induced haemorrhagic cystitis

Thymoquinone (TQ), the most prominent constituent of Nigella sativa seeds, essential oil, is reported to possess an organ protective effect via Nrf2 expression and activation of Phase-II antioxidant enzymes. Haemorrhagic cystitis is the sudden onset of haematuria combined with bladder pain and irritable bladder symptoms are the known toxic effects of cyclophosphamide (CYP) chemotherapy. The objective of the present study was to investigate and compare the protective effect of thymoquinone (TQ) and thymoquinone nanoparticles (TQ-NP) in the kidney against CYP-induced haemorrhagic cystitis. Primarily, TQ-NP was fabricated by synthesis of N-acetylated chitosan and nanoparticle preparation by the ionic gelation technique. They were characterized by particle size, polydispersive index (PDI), zeta potential, entrapment efficiency (EE), SEM, and dynamic scattering calorimetry (DSC). Moreover, fluorescein isothiocyanate (FITC) labeled NPs were prepared for biodistribution studies. The protective mechanisms of TQ-NP included its anti-inflammatory activity, inhibitory effects on cytokine levels, and protection against the DNA damage in the bladder epithelium. The cystitis was induced in rats by orally administering 200 mg/kg of CYP. The dose-dependent protective effect of the TQ-NP was determined by intravenously administering 1, 2, and 5 mg/kg of the TQ-NP to CYP-treated rats. The present study revealed that the TQ-NP prepared by ionic gelation method provides kidney targeted delivery of TQ as compared to TQ solution. The mean particle size, PDI, and %EE of TQ-NP were 272.6 nm, 0.216, 70.81 ± 0.12% respectively. The zeta potential of thymoquinone-loaded nanoparticles was found to be −20.7 mV and − 22.6 mV respectively before and after lyophilization. SEM study also confirmed the small size and spherical shape. Pharmacokinetic studies revealed the improvement in half-life and prolonged action of the TQ-NP as compared to the TQ solution. Also, TQ-NP administration showed more protection against the characteristic histological alterations in the bladder in comparison to TQ solution. The present study indicates that TQ-NP exerts potent anti-oxidant, DNA protective and cytokine inhibitory activity at considerably lower concentrations as compared to plain TQ solution. The nano formulation of TQ using N-acetylated chitosan provides effective kidney targeted delivery of TQ, which in turn improves its retention and protective efficacy against CYP-induced haemorrhagic cystitis.

Cyclophosphamide induced physiological and biochemical changes in mice with an emphasis on sensitivity analysis

The widespread use of cyclophosphamide (CP) in medical treatment had caused ubiquitous contamination in the environment. To data, many studies have been carried out on the toxic effect of CP. However, among these toxic effects of CP, which are the most sensitive remains unclear. Present study aimed to investigate the toxicity of CP on mice and evaluate the sensitivity of physiological-biochemical parameters upon exposure of mice to CP. Results showed that as compared with the control group, CP caused significant reduction in body weight (p < 0.01), spleen coefficient (p < 0.01), leukocyte density (p < 0.01) and alanine transaminase (ALT) in kidney (p < 0.01); However superoxide dismutase (SOD), malondialdehyde (MDA), ALT in liver and creatinine (Cr) in kidney significantly (p < 0.05) increased. Among the suppressed physiological and biochemical parameters, the sensitivity to CP toxicity was generally ranked as body weight > leukocyte density > ALT in kidney > spleen coefficient; while among the stimulated parameters, the sensitivity was ranked as MDA (liver) > Cr (kidney) > ALT (liver). Overall, the most sensitive parameters to CP toxicity may be associated with growth, immune system and the normal function of liver and kidney.

Evaluation of nephroprotective effect of rutin against toxic effect of cyclophosphamide

Cyclophosphamide (CYP) is an alkylating anti-tumor drug. CYP has many adverse effects, partly due to oxidative stress induction in various tissues. Rutin is one of the natural flavonoids with strong antioxidant properties. The aim of this study was to determine the nephrprotective effect of rutin against toxic effect of cyclophosphamide. The study was performed on swiss albino mice. Thirty male mice were divided into six group. The first group received normal saline for 14 days. The second group received only cyclophosphamide drug 25 mg/kg., i.p. on 0 to 14 days. The third group received amifostine drug prior 1hour before the administration along with cyclophosphamide (25mg/kg) respevtively for 14 days. The group fourth and five received 40mg/kg and 80mg/kg of rutin after the administration of cyclophosphamide (25mg/kg) respectively for 14 days. Cyclophosphamide administration significantly (P

Protective Effects of Evening Primrose Oil against Cyclophosphamide-Induced Biochemical, Histopathological, and Genotoxic Alterations in Mice.

Cyclophosphamide (CP) is a well-known antineoplastic agent; however, its clinical use can be associated with various organ toxicities. Evening primrose oil (EPO) contains several phytoconstituents with potent anti-oxidant and anti-inflammatory activities. This experimental study was performed to investigate the chemoprotective effects of EPO in the liver and pancreas of CP-intoxicated mice. Thirty-two albino mice were randomly divided into 4 equal groups: group I received saline (control mice), group II were treated with CP at 100 mg/kg/day for two subsequent days, and groups III and VI were treated with 5 and 10 mg/kg/day bw EPO, respectively for 14 days, followed by two doses of CP at the 15th and 16th days of the experiment. Then, mice were sacrificed and histopathological examinations, biochemical studies, and DNA laddering tests were conducted for hepatic and pancreatic tissues. Cyclophosphamide-intoxicated mice showed significant increases (p < 0.05) in the serum levels of liver enzymes, pancreatic amylase and tissue levels of malondialdehyde, and TNF-α, as well as a significant decrease (p < 0.05) in the serum insulin level. In addition, both hepatic and pancreatic tissues showed disturbed tissue architecture, hydropic degeneration, congested vessels, and inflammatory infiltrates, as well as increased DNA fragmentation. In a dose-dependent manner, pretreatment with EPO was associated with significant improvements (p < 0.05) in all biochemical parameters and significant amelioration of histopathological alterations and DNA fragmentation in CP-intoxicated mice. Pretreatment with EPO showed significant antioxidant, anti-inflammatory, and genoprotective effects against the toxic effects of CP in mice hepatic and pancreatic tissues.

Effect of Capparis spinosa L. Leaf bud Extract on The Hematological and Histological Changes Induced by Cyclophosphamide in Mice

Medicinal plants have been suggested to be chemoprotective on account of antioxidants and antitoxic properties. Capparis spinosa L. one of the medicinal plants is widely used in folk medicine. Therefore, the present study aimed to find a protective efficacy of ethanolic and aqueous extract leaf bud of C. spinosa against toxic effects of cyclophosphamide (CP) in mice. Results showed significant decreasing (p=0.05) in red blood cells (RBCs) hemoglobin (HB), packed cell volume (PCV%) and platelets count (PLT) reach to 7.36×1012/L, 96.83g/L, 31.6% and 925.0×1012/L respectively, in blood of mice treated with CP compared with control group which was 8.58×1012/L, 122.33g/L, .44.41% and 2194.16×1012/L, respectively. Significant decreasing in the values of white blood cells number (WBCs), and percentage of lymphocyte and monocyte, reach to 3.36×109/L,26.61% and 4.86% in blood of mice treated with CP compared with control. Significant increasing were showed in some liver enzymes (AST, and ALT) when exposed to CP which reach to 166.0U/L and 63.16U/L respectively, compared with control group. While groups treated with extract showed non significant differences compared with control group in the values of blood parameters and enzymes. Histopathological changes in liver when mice treated with CP represent by dilated of central vein, swelling of hepatocyte, focal accumulation of inflammatory cells, excessive vacuolated of hepatocyte, glycogenic degeneration, congested of central vein with sinusoid, and vacuolated of cytoplasm of hepatocytes with irregular nucleolus. While kidney showed degeneration of epithelial cells as foaming lumen, Clear hemorrhagic interstitial some of renal tubules are closure with degeneration of epithelial cells, Congestion of blood vessels. The tissues of kidney showed cloudy swelling of epithelial cells and hemorrhages, some of cells were elongated towered lumen, and there were inflammatory cells in interstitial tissue. Results showed the important role of leaf bud extract of C. spinosa in keeping the normal values of blood parameters and prevent histological changes as control.

ПРОТЕКТОРНЫЕ СВОЙСТВА ДИАРИЛГЕПТАНОИДА ОРЕГОНИНА ПРИ ВВЕДЕНИИ ЖИВОТНЫМ ЦИКЛОФОСФАМИДА

Background. Diarylheptanoids administration increases the efficacy of cyclophosphamide and reduces the activity of lipid peroxidation processes, allowing to decrease the dose of a cytostatic agent and reduce its side effects. The purpose of the study was to determine the protective properties of diarylheptanoid oregonin against the toxic effects of cyclophosphamide on the leukocyte count and the concentration of free amino acids in the blood plasma and spleen tissue. Material and methods. Male rats treated with cyclophosphamide (160 mg/kg body weight) and oregonin (5 mg/kg body weight) were used in the study. The determination of free amino acids was performed by the reversed-phase HPLC. Results. It has been established that the administration of a course of oregonin together with cyclophosphamide increases the content of amino acids and their derivatives in blood plasma as well as the availability of proteinogenic amino acids in spleen cells. Conclusion. Administration of a course of oregonin together with cyclophosphamide has a protective effect against the amino acid imbalance in the blood plasma and spleen tissue.

Effect of Tangeritin Against Cyclophosphamide-Induced Toxicity in the Larvae of Transgenic Drosophila melanogaster (hsp70-lac Z) Bg9

ABSTRACTTangeritin is a pentamethoxy flavone found in tangerine and other citrus peels. The present study was conducted to study the effect of various doses of tangeritin on the toxic effects induced by cyclophosphamide (CP) in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9. Commercially available tangeritin and CP were used. CP was used alone at 20 µM of food concentration and with 20, 40, and 80 µM of tangeritin. The exposure of the third instar larvae to 20µM of cyclophosphamide alone results in significant hsp 70 expression along with tissue, DNA, and oxidative damage. The exposure of the third instar larvae to 20 µM of CP along with 20, 40, and 80 µM of tangeritin results in a dose-dependent decrease not only in hsp 70 expression but also in tissue, DNA, and oxidative damage. The results of the present study suggest that tangeritin has a protective role against the toxic effects of cyclophosphamide in the third instar larvae of transgenic Drosophila melanogaster (hsp 70-lac Z)Bg9.

Correction of the toxic effect of cyclophosphamide on hemopoiesis in animals with lewis lung carcinoma using low-molecular-weight sodium alginate

The influence of low-molecular-weight sodium alginate, which is administered as an isolated agent and in combination with cyclophosphamide, on the parameters of peripheral blood and bone marrow was studied in mice with Lewis lung carcinoma. It was shown that administration of sodium alginate with a molecular weight of 1–10 and 20–30 kDa to tumor-bearing animals prevents bone marrow failure by activating the process of regeneration of granulocytic hemopoietic stem cells that are damaged by a single injection or repetitive injections of a cytostatic agent, due to stimulation of the clonal activity of granulocytopoiesis precursors. As a result, this treatment prevents the progression of leukopenia.

Examination of the cyclophosphamide-induced polyneuropathy on guinea pig sciatic nerve and gastrocnemius muscle with differential scanning calorimetry

Polyneuropathy is defined as a simultaneous malfunction of several peripheral nerves, which could be a side effect of cancer therapy; however, this is reported to occur rarely and difficult to prove. The purpose of the study was to introduce for the first time the calorimetry in the diagnosis of neuropathy in an experimental animal model. The study was inspired by the forensic investigation of a 53-year-old cancer survival female patient, in whose case the development of polyneuropathy could have been caused by cyclophosphamide therapy. Adult guinea pigs were injected intraperitoneally with the dose of cyclophosphamide that comparable to the human dosage. Animals were euthanized; nerve and muscle samples were analyzed by a SETARAM Micro calorimeter. The denaturation temperatures were measured and the calorimetric enthalpies were calculated based on the areas under thermal absorption curves. The thermal denaturation of the samples decreased and the calorimetric enthalpy increased, depending on the therapeutic cyclophosphamide doses. The nerves were more sensitive to chemotherapy, compared to the muscles. The toxic effects of cyclophosphamide on peripheral nerves and muscles can be measured and analyzed by calorimetry, which effects were found dose dependent.

Abstract 5111: Protective effect of Traditional Chinese Medicine formula LQ against cyclophosphamide-induced renal damage in nude mice.

Abstract TCM formula LQ is an herbal cocktail. Cyclophosphamide (CYC) is widely used in cancer chemotherapy. However renal damage is a dose-limiting side effects of CYC. In the current study, we determined if LQ can protect against damage. The heart, liver, spleen, lung, kidney, and intestine of a mouse from control, LQ pretreatment, CYC pretreatment, and CYC+LQ treatment were stained with HE. The histology of each organ was observed under microscopy. The histology of the heart, liver, spleen, lung and intestine showed normal histopathological structure in all groups. The kidneys in the control mice, LQ pretreated mice, and CYC+LQ pretreated mice showed normal architecture of kidney cortex and medulla. The cortex showed normal renal corpuscle, proximal convoluted tubules, and distal convoluted tubules. The inner medulla and outer medulla all contained a thick ascending limb of the loop of Henle, and interstitial connective tissue. However, kidney of the CYC pretreatment mice showed damage in structures compare with other groups. The toxic effect of CYC on the kidney involved the glomeruli, the tubules, and the interstitium. The structures of the cortex in CYC pretreated group showed disconnection between glomeruli and tubules. The ducts in the medulla were destroyed. LQ also protected against weight loss and cachexia induced by CYC. LQ may be a promising drug for combination with CYC to improve its therapeutic index. Citation Format: Lei Zhang, Chengyu Wu, Robert M. Hoffman. Protective effect of Traditional Chinese Medicine formula LQ against cyclophosphamide-induced renal damage in nude mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5111. doi:10.1158/1538-7445.AM2013-5111

The tumor cured, but what about the patient?

Polyneuropathy is defined as a simultaneous malfunction of several peripheral nerves, which could be a toxic side effect of cancer therapy; however, this is reported to occur rarely and difficult to confirm. The purpose of the study was to introduce, at the first time, the calorimetry in the diagnosis of neuropathy in an experimental animal model. The study was inspired by the forensic investigation of a 53-year-old cancer survivor female patient, in whom the development of polyneuropathy could be caused by cyclophosphamide therapy. Adult guinea pigs were injected intraperitoneally with the dose of cyclophosphamide, comparable to the human dosage. Animals were euthanized, then nerve and muscle samples were analyzed using a SETARAM Micro calorimeter. Denaturation temperatures were measured and the calorimetric enthalpies were calculated based on the areas under thermal absorption curves. Thermal denaturations of the samples were decreased and the calorimetric enthalpies were increased depending on the doses of cyclophosphamide. The nerves were more sensitive to chemotherapy as compared to the muscles. It is concluded that toxic effects of cyclophosphamide on peripheral nerves and muscles can be measured and analysed by calorimetry, and that the effect was dose dependent.

Chemoprotective effect of ascorbic acid, α-tocopherol, and selenium on cyclophosphamide-induced toxicity in the rat ovarium

ObjectiveThe aim of the study was to evaluate the protective efficacy of ascorbic acid, α-tocopherol, and selenium by measuring the glutathione (GSH) levels and proliferating cell nuclear antigen (PCNA) and growth differentiation factor-9 (GDF-9) expression in the ovarian tissues of rats treated with cyclophosphamide (CP) therapy. MethodsFemale Wistar rats were divided into 5 groups of 6 rats each: (I) control, (II) only CP, (III) CP + ascorbic acid, (IV) CP + α-tocopherol, and (V) CP + selenium. Immunohistochemical stainings and GSH protocol were then applied. ResultsFollowing CP administration, the rats exhibited significantly lower GDF-9 expression in oocytes and PCNA expression in granulosa cells of follicles in all stages of development (P < 0.05). In CP + antioxidant groups (Groups III, IV, V), GDF-9 immunoreaction in oocytes and PCNA immunoreaction in granulosa cells of the developing follicles were found to show an increase towards the levels observed in the control group (P < 0.05). ConclusionsCP was found to cause remarkable degenerative effects in normal ovarian tissue, and we believe that this damage can be reduced and ovarian tissue can be spared from the toxic effects of CP by using antioxidants such as ascorbic acid, α-tocopherol, and selenium.

Synergestic effect of lycopene and Melatonin against the genesis of oxidative stress induced by cyclophosphamide in rats

Cyclophosphamide (CP) is an alkylating agent that has been considered effective for cancer treatment. Lycopene, the pigment in tomato fruits, has beneficial effect in the treatment of some diseases. The goal of this study is to evaluate the protective effect of lycopene alone or combined with melatonin (Mel) in inhibiting the oxidative stress and toxic effect of CP in rats. Five groups of rats were included in this study; Group I served as the control. Rats in groups II-V were administrated with single dose of CP (150 mg/kg B.W) interperitoneally for 3 days. On the same day of CP administration, the rats in group III were fed a diet supplemented with lycopene (50 mg/kg of diet), rats in group IV were administered with a dose of 2.5 mg Mel/kg body weight (bw) injected subcutaneously and rats in group V were supplemented with lycopene and a dose of 2.5 mg Mel/kg bw injected subcutaneously. After 15 days the blood samples were collected. Results obtained showed that CP exerted its toxic effect by increasing the free radicals and reactive oxygen species that causes lipid peroxidation and cell damage, and this in turn is detected by elevation in nitric oxide (NO) and malondialdehyde (MDA), while the activities of antioxidants enzymes including (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) were significantly decreased as compared with the control rats. The combined treatment (Lyco + Mel) group showed potential reduction in these parameters more than those treated with lyco alone. The activities of SOD, CAT and GPx were found significantly high than lyco alone treated rats. A positive significant correlation between NO and MDA (r = .81). In conclusion, these results suggested that supplementation of diet with lycopene and Mel provided antioxidant defense with strong chemopreventive activity against Cp-induced cytotoxicity.

Modulatory Effect of a Unani Formulation (Jawarish amla sada) on Cyclophosphamideinduced Toxicity in Tumour Bearing Mice

Aims: Our aim was to study the modulatory effect of a Unani herbal formulation Jawarish amla sada against cyclophosphamide-induced toxicity in tumour bearing mice. Study Design: Non randomized control study. Place and Duration of Study: The study was conducted at the Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi during 2008-10. Methodology: Study was conducted in Swiss albino mice divided in five groups (n=6). Animals were challenged with Ehrlich’s ascites tumour cells (1x10 cells). Cyclophosphamide (50 mg/kg body weight), an alkylating anticancer drug that especially affects humoral immune functions, was injected intraperitoneally in a single dose. The protective effect of Unani drug Jawarish amla sada (250 mg/kg body weight) was studied in tumour bearing animals treated with cyclophosphamide. Immune function assessment Research Article British Journal of Medicine & Medical Research, 2(3): 454-468, 2012 455 test such as plaque forming cell assay (PFC) and biochemical parameters such as activities of antioxidant enzymes and reduced glutathione were measured in mice. Results: Jawarish amla sada significantly modulated the immunosuppressive effect of cyclophosphamide as compared to the group treated with cyclophosphamide. Jawarish amla sada also protected activities of antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase and significantly restored level of reduced glutathione in liver and kidney of tumour bearing mice exposed to cyclophosphamide. Similar protective effect of Jawarish amla sada was observed against elevated lipid peroxidation in these tissues. Conclusion: Jawarish amla sada showed potential to provide protection against toxic effects of cyclophosphamide in tumour bearing mice. The mechanism of action of the drug may be attributed to various antioxidants fortified in this herbal Unani formulation, which is used in the traditional system of medicine in Indian subcontinent against several liver ailments.

Modulatory Effect of a Unani Formulation (Jawarish amla sada) on Cyclophosphamide-induced Toxicity in Tumour Bearing Mice

Aims: Our aim was to study the modulatory effect of a Unani herbal formulation Jawarish amla sada against cyclophosphamide-induced toxicity in tumour bearing mice. Study Design: Non randomized control study. Place and Duration of Study: The study was conducted at the Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi during 2008-10. Methodology: Study was conducted in Swiss albino mice divided in five groups (n=6). Animals were challenged with Ehrlich’s ascites tumour cells (1x10 cells). Cyclophosphamide (50 mg/kg body weight), an alkylating anticancer drug that especially affects humoral immune functions, was injected intraperitoneally in a single dose. The protective effect of Unani drug Jawarish amla sada (250 mg/kg body weight) was studied in tumour bearing animals treated with cyclophosphamide. Immune function assessment Research Article British Journal of Medicine & Medical Research, 2(3): 454-468, 2012 455 test such as plaque forming cell assay (PFC) and biochemical parameters such as activities of antioxidant enzymes and reduced glutathione were measured in mice. Results: Jawarish amla sada significantly modulated the immunosuppressive effect of cyclophosphamide as compared to the group treated with cyclophosphamide. Jawarish amla sada also protected activities of antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase and significantly restored level of reduced glutathione in liver and kidney of tumour bearing mice exposed to cyclophosphamide. Similar protective effect of Jawarish amla sada was observed against elevated lipid peroxidation in these tissues. Conclusion: Jawarish amla sada showed potential to provide protection against toxic effects of cyclophosphamide in tumour bearing mice. The mechanism of action of the drug may be attributed to various antioxidants fortified in this herbal Unani formulation, which is used in the traditional system of medicine in Indian subcontinent against several liver ailments.

Protective role of curcumin against the toxic effects of cyclophosphamide in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9

In the present study the effects of curcumin was studied against the toxic effects induced by 0.025 and 0.050 ml/ml of cyclophosphamide (CP) in the third instar larvae of transgenic &lt;em&gt;Drosophila melanogaster (hsp70-lacZ)Bg9&lt;/em&gt; using hsp70 expression and dye exclusion test as a parameter. The exposure of the third instar larvae to 0.025ml/ml of CP along with 1, 5 and 10 mg/ml of curcumin results in the dose dependent significant decrease in the &lt;em&gt;hsp70&lt;/em&gt; expression and tissue damage for 12, 24 and 48hr of duration. Similar results were obtained with the exposure of third instar larvae to 0.050 ml/ml of CP along with 1, 5 and 10 mg/ml of curcumin. The selected doses of curcumin i.e. 1, 5 and 10 mg/ml were not toxic but reduced significantly the expression of &lt;em&gt;hsp70&lt;/em&gt; and tissue damage induced by CP. The results of the present study suggest that the curcumin has a protective role against the toxic effects of CP in the third instar larvae of transgenic &lt;em&gt;Drosophila melanogaster (hsp70-lacZ)Bg9&lt;/em&gt;.

Therapeutic Effects of Aloe Vera Plant Extract Against Cyclophosphamide and Buthionine Sulfoximine Induced Toxicities in the Bladder

Bladder toxicity is one of the most troublesome side effects associated with chemotherapeutic treatments of cancer involving the use of cyclophosphamide (CP) and buthionine-SR-sulfoximine (BSO). The present study was undertaken to investigate the effects of pre-treatment with an Aloe vera plant extract (AVE) on the urotoxicity induced by acute doses of CP and BSO using a Swiss albino mice model. The modulation of toxicity was evaluated by measuring lipid peroxidation (LPO), peroxide hydrogen production (H2O2) and antioxidants in the urinary bladder of the animals. The findings revealed that Aloe vera induced remarkable protective effects in terms of both LPO and enzymatic antioxidant activities. The CP-treated mice were noted to undergo significant decreases in the activities of glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GP), and catalase (CAT) when compared to the controls. The levels of reduced glutathione (GSH) also decreased with an increase in LPO in the CP-treated animals and BSO treatment exerted an additive toxic effect in the CP-treated animals. Pre-treatment with the Aloe vera herbal extract restored all enzymatic activities back to normal, thus confirming its overall protective effect against the toxic effects of CP and BSO. The potential effect of AVE to prevent CP and BSO induced urotoxicity was also reflected by the histological analysis, indicative of its uroprotective effects. The restoration of GSH through treatment with Aloe vera may play an important role in the reversal of CP-induced apoptosis and free radical mediated LPO in urinary bladder. Due to its widespread availability in nature and relative lack of toxicity, the Aloe vera plant extract presented in the current study could be considered a potential strong candidate for future applications as an adjutant to cancer chemotherapies.