Cyclophosphamide-induced Toxicity Research Articles

Quercetin, chrysin, caffeic acid and ferulic acid ameliorate cyclophosphamide-induced toxicities in SH-SY5Y cells

Clinical use of cyclophosphamide (CP) causes apoptosis-induced cell death in the immune system, liver, heart and kidneys. To prevent the cells against side effects of CP and its metabolites, increasing antioxidant defence mechanism of the body with supplemental antioxidants is important. Therefore, there is a requirement for effective agents which could prevent the healthy cells from the harmful effects of drug-induced toxicities. Several antioxidants have been used in protecting or alleviating CP-induced cell death. However, no such study is reported in CP-induced SH-SY5Y cell toxicity. The aim of this study was to evaluate likelihood ameliorative effects of caffeic acid, chrysin, quercetin and ferulic acid against CP-induced toxicity in SH-SY5Y neuron cells.In this study protective effects of quercetin, chrysin, caffeic acid and ferulic acid against CP-induced cell toxicity in SH-SY5Y cells was evaluated by cell proliferation assay, lipid peroxidation (LPO) analysis to decipher antioxidant capacity, tunel assay and qRT-PCR experiments to examine anti-apoptotic activities of the antioxidants. The results showed that CP-induced cell toxicity in SH-SY5Y cells and treatments with the antioxidants suppressed the cell death. Our results suggests that these anti-oxidants protected SH-SY5Y cells via a decrease in LPO levels, downregulating the expression of Cas-3, Cyt c and Bax and upregulating expression of anti-apoptotic gene Bcl-2.The use of antioxidant as nutritional supplements, and in particular of caffeic acid, chrysin, quercetin and ferulic acid, reduce apoptotic effects of CP in SH-SY5Y cells that could add insight into therapeutic approaches to CP-induced cell injuries.

Effect of hydroalcoholic Allium atroviolaceum L. on the pathology of testicular tissue in cyclophosphamide-treated mice.

BackgroundThe most important side effects of Cyclophosphamide, as an anticancer broad-spectrum drug, are the negative effects on the reproduction and fertility because of oxidative stress. Considering the antioxidant properties of medicinal plants, especially those of the Allium genus, this paper studied the effect of hydroalcoholic extract of Allium atroviolaceum L. on the pathology of testicular tissue in CP-treated mice.MethodsGroups of this experimental study consisted of normal saline recipients; three groups receiving A. atroviolaceum extract at 50, 100, 200 mg/kg; three groups receiving A. atroviolaceum extract at 50, 100, and 200 mg/g and 6.6 mg/kg of Cyclophosphamide; and a group given Cyclophosphamide at 1.6 mg/kg. All injections were performed intra-peritoneally. After 30 days, the testicular histological profile as well as the number of spermatozoa, the number of primary and round spermatocytes, and the number of spermatogonia were investigated.ResultsCyclophosphamide treatment significantly reduced the lumen diameter, the seminiferous tubule diameter, the epithelial thickness, as well as decreased the quantity of spermatozoa and round and primary spermatocytes compared to the control group. Cyclophosphamide groups treated with A. atroviolaceum extract at 50, 100 and 200 mg/kg in a significant manner improved these variables (P < 0.001).ConclusionA. atroviolaceum extract can significantly improve Cyclophosphamide-induced toxicity and pathological process on testicular tissue. It seems that this plant, with high antioxidant capacity, can be considered a complementary therapy for Cyclophosphamide to prevent undesirable effects on the reproductive system.

Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1

Purpose: Cancer rates have been increased among women of reproductive age nowadays. Hence, many young female will be exposed to chemotherapeutic agents as cyclophosphamide (CP), carrying the hazards on female fertility. Cilostazol is a selective phosphodiesterase-3 inhibitor drug which exhibits antioxidant, anti-inflammatory, and anti-apoptotic activities. We aimed in this study to explore the possible protective effects of cilostazol against CP-induced ovarian damage in female rats.Methods: Cilostazol (10 mg/kg/day) was administered orally for 10 days in presence and absence of CP (150 mg/kg IP single dose) treatment. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and anti-Müllerian hormone (AMH) levels were determined. Ovarian oxidative stress parameters along with inflammatory biomarkers were measured. 3,5-Cyclic adenosine monophosphate (cAMP) ovarian level was detected. Ovarian histopathological examination and caspase-3 immunohistochemical study were evaluated.Results: CP-treated rats showed a significant increase in serum levels of FSH and LH with decreased serum E2 and AMH levels with an increase in the ovarian inflammatory and oxidative stress biomarkers besides a significant decrease in cAMP ovarian level with an evident histopathological picture of ovarian damage and a high caspase-3 immunoexpression. Cilostazol pretreatment significantly restored the distributed hormonal levels, the oxidative stress and inflammatory biomarkers to their normal levels with marked improvement in histopathological picture of ovarian damage with a significant decrease in caspase-3 immunoexpression.Conclusions: These data suggest that cilostazol protects against CP- induced ovarian damage, which may be related to an increase in cAMP with subsequent anti-inflammatory, antioxidant, and anti-apoptotic properties.

Protective Effect of Vitamin C and Zinc as an Antioxidant Against Chemotherapy-Induced Male Reproductive Toxicity.

Treatment with anticancer drugs such as cyclophosphamide can harm the male reproductive system. Vitamin C and zinc are micronutrients with antioxidant activity and are the essential components of semen. Therefore, this study aimed to evaluate whether cyclophosphamide-exposed mice can recover from fertility with vitamin C and zinc therapy.In this experimental study, fifty male mice were divided into five groups. Groups 1-4 received cyclophosphamide (100 mg/kg, once a week for eight weeks). Also, group 2 received zinc (200 mg/kg), group 3 received vitamin C (300 mg/kg), group 4 received zinc and vitamin C (200 mg/kg and 300 mg/kg, respectively), five times per week for eight weeks, and group 5 received normal saline once a week and water five days a week for eight weeks. The data collected were statistically analyzed using SPSS 22.Results showed a significant increase in mount latency and a significant decrease in the number of sperms in the cyclophosphamide group compared to the control group. However, mount latency has been significantly decreased in mice treated with cyclophosphamide plus zinc compared to the cyclophosphamide group. The study also showed that the sperm count in the group that received cyclophosphamide and zinc had been increased compared to the cyclophosphamide group; the other treatments have decreased mount latency and increased the sperm count compared to the group treated with cyclophosphamide but not significantly. The Tubule Differentiation Index showed an increase in the cyclophosphamide-Zinc-Vitamin C group in comparison with the cyclophosphamide group.The current study showed that zinc could improve cyclophosphamide-induced toxicity of the reproductive system in male mice.

Inhibition of NF-kB Pathway by Gggulsterone in the Protective Effects of Cyclophosphamide-Induced Renal Toxicity

Cyclophosphamide which acts as cytotoxic alkylating agent can induce a renal damage through the toxic metabolites which result from metabolic activation of Cyclophosphamide by cytochrome P-450 inside hepatocyte and develop renal toxicity by direct binding with cellular organelles in the urinary tract cells. Guggulsterone is a sterol derived from plant has ability to bind to farsenoid X receptor, mineral corticosteroid receptor, androgen receptor, glucocorticoid receptor and estrogen receptor.

Protective Effects of Boron on Cyclophosphamide-Induced Bladder Damage and Oxidative Stress in Rats.

This study aims to investigate protective effects of boron against cyclophosphamide-induced bladder toxicity that produces oxidative stress and leads to apoptosis of the cells. In total, 24 rats were divided into 4 equal groups. The control group received saline. The 2nd experimental group received 200mgkg of cyclophosphamide i.p. on the 4th day while the 3rd group was given only boron (200mgkg, i.p.) for 6days. In the 4th group, boron was given for 6days and cyclophosphamide (200mgkg, i.p.) was administrated on the 4th day. Twenty-four hours after the last boron or cyclophosphamide administration, rats were sacrificed under anesthesia. Bladder tissues of rats were taken for histological and immunohistochemical (apoptotic markers such as caspase-3, bcl-2, and bax) and blood was taken for the biochemical (serum total thiol, serum natural thiol, serum thiol-disulfide) analysis. Transient epithelial thinning, edema, marked inflammatory reaction, and bleeding were observed in bladders of the group that received cyclophosphamide. Also, the activity of bax and caspase-3-positive cells increased while the number of bcl-2-positive cells decreased. In the same group, serum natural thiol and total thiol levels decreased while serum disulfide levels increased, which indicates oxidative stress. On the other hand, in the boron+cyclophosphamide group pretreatment with boron protected, the bladder tissue and the number of bcl-2-positive cells increased, and bax and caspase-3-positive cells decreased, showing antiapoptotic effects of boron against cyclophosphamide-induced toxicity. In parallel with the findings of this group, native thiol and total thiol levels increased and serum disulfide levels decreased pointing out to a decreased oxidative stress. Our results indicate that boron pretreatment significantly protects rat bladder against cyclophosphamide-induced bladder damage due to its antiapoptotic and antioxidant properties.

Chemoprotective activity of aqueous leaf extract of Acalypha wilkesiana against cyclophosphamide-induced toxicity in rats

Objective: To investigate the protective effect of aqueous leaf extract of Acalypha (A.) wilkesiana Muell. Arg (Euphorbiaceae) against cyclophosphamide-induced toxicity in albino rats. Methods: Twenty male albino rats were randomly divided into five groups of four animals each. The control group (I) was fed with pellets and distilled water, while group II was orally administered with only 20 mg/kg cyclophosphamide. Groups III, IV and V were co- administered with 20 mg/kg body weight cyclophosphamide and 110, 220 and 440 mg/kg body weight A. wilkesiana leaf extract, respectively, for 7 d. After treatment, liver and kidney function biomarkers, haematological parameters, liver antioxidants, and mitochondrial membrane permeability transition pore opening were investigated. Results: A. wilkesiana leaf extract significantly reduced (P Conclusions: This study demonstrates that aqueous extract of A. wilkesiana leaf protected tissues against cyclophosphamide-induced oxidative damage.

The potential protective role of coenzyme q10 on the cyclophosphamide-induced lung toxicity in adult male albino rats: a histological and ultrastructural study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Cyclophosphamide is anticancer and immunosuppressant agent used to treat malignant and autoimmune diseases. Its long-term use causes side effects, as infertility and pulmonary toxicity. Coenzyme Q10; the only synthesized antioxidant in human body, acts as powerful antioxidant, scavenging free radicals, and inhibiting lipid peroxidation. Aim of present study was to examine effect of coenzyme Q10 on blood biochemical profiles, histopathological changes in lungs of adult rats exposed to cyclophosphamide-induced toxicity.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; 36 adult male albino rats divided into four groups; control and three experimental each having 9 rats. First experimental group received coenzyme Q10, second received cyclophosphamide while third group received coenzyme Q10 along with cyclophosphamide. Experiment lasted for 7 days. On 8th day, animals were sacrificed by decapitation. Lung tissue samples were collected for histopathological examination. SOD (superoxide dismutase) and MDA (malondialdehyde) levels were determined and used for statistical analysis. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; In coenzyme Q10 treated group, H&amp;amp;E stained sections revealed normal respiratory alveoli. Ultrathin sections revealed normal alveolar septa, pneumocyte and blood capillaries contain erythrocytes. In cyclophosphamide treated group, H&amp;amp;E stained sections revealed peribronchial and interstitial fibrosis. Ultrathin sections revealed alveoli having apparent free lumen with extravasated erythrocytes. Alveolar septa revealed collagen fibrils deposits, and proliferated fibroblasts. In combined coenzyme Q10 and cyclophosphamide treated group, H&amp;amp;E stained sections revealed marked decrease of inter-alveolar tissue thickening. Ultrathin sections revealed destructed alveolar septa with dissociated remnants of collagen fibrils. Blood capillaries appeared wide, containing monocytes and erythrocytes.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Administration of coenzyme Q10 with cyclophosphamide is advised to alleviate cyclophosphamide-induced lung toxicity.&lt;/p&gt;

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.

Fullerene C60 nanoparticles ameliorated cyclophosphamide-induced acute hepatotoxicity in rats

Cyclophosphamide (CP), a chemotherapeutic agent, induces hepatotoxicity as one of its side effects. Therefore, the aim of the present study is to investigate the potential hepatoprotective effects of fullerene C60 nanoparticles (C60) against the high toxic dose of CP. Twenty five albino rats were randomly assigned to 5 groups (n=5 per group). Group 1 served as a control. Group 2 received 200mg/kg of CP once intraperitoneally, while group 3 treated with the same CP dose plus C60 (4mgkg, orally) daily for 10days. Group 4 exposed CP and ZnCl2 (4mgkg, orally) daily for 10days. Group 5 exposed to CP and co-treated with C60 and ZnCl2. One day after last treatment, blood and livers were collected for hematological, biochemical and histopathological investigations. C60 normalized significantly RBCs, HB, PCV, WBCs and platelets numbers compared to CP-exposed rats. Moreover, liver enzymes namely ALT, AST and ALP revealed that CP elevated their levels and C60 significantly (p<0.05) reduced them to basal levels. The level of oxidative stress marker namely, MDA was elevated upon CP exposure and normalized by C60 treatment. In addition, antioxidant systems e.g. GSH, CAT and SOD were depleted from liver tissue due to CP toxicity these were recovered by C60 administration. The hepatoprotective effects of C60 on tested parameters were comparable with ZnCl2 and neither additive nor synergistic effect was observed. Histopathogically, severe liver degeneration was recorded after CP treatment, however, only mild changes were observed after C60 administration. Our data suggest that C60 improves both blood and hepatic parameters altered by cyclophosphamide-induced toxicities. The current study is of clinical relevance particularly, application of C60 as a monotherapy or in combination to ameliorate the CP side effects in cancer-treated patients.

Aggravation of cyclophosphamide-induced reproductive toxicity in mice by aqueous extract of Aegle marmelos (L.)

Aegle marmelos (L.) (Rutaceae) commonly known as bael is an important medicinal fruit tree. The present study focused on the effects of aqueous extract of Aegle marmelos (AEAM) on the testis and sperm characteristics induced by cyclophosphamide (CPA) in mice. Thirty six adult Parke’s strain mice were divided into six groups: group I given only distilled water (control); group II administered with AEAM alone once in a week for five weeks; group III administered with CPA (200 mg/kg b.w., intraperitoneally) once in a week for five weeks and group IV-VI CPA along with AEAM (400, 500 and 600 mg/kg b.w., orally). CPA was found to reduce gonadosomatic index (GSI), sperm counts, motility, viability, antioxidant activities and induced histopathological changes of testis. In the group administered AEAM with CPA an exacerbation of sperm count, motility and viability of the cauda epididymis, GSI, antioxidant activities and architecture of testis was observed. The results suggest that the administration of AEAM may aggravate CPA-induced reproductive toxicity. It may be helpful in preparation of natural male contraceptives.

Combined protective effect of zinc oxide nanoparticles and melatonin on cyclophosphamide-induced toxicity in testicular histology and sperm parameters in adult Wistar rats

Cyclophosphamide (CP) has been known as an anticancer drug with several side effects on various organs such as a male reproductive system that can cause infertility. To evaluate the possible combined effects of zinc oxide nanoparticles (nZno) and melatonin (Mel) on sperm parameters and histopathological changes of the testis in CP-treated rats. 42 adult male Wistar rats were divided into six groups. GI: control, GII: 60 mg/kg/wk CP, GIII and GIV, 10 mg/kg/wk Mel and 5mg/kg/wk nZno and GV: 5 mg/kg/wk nZno and 10 mg/kg/wk Mel were given 2 hr prior to CP injection, respectively,GVI: 5mg/kg/wk nZno and 10 mg/kg/wk Mel simultaneously. After 8 wk of treatment, rats were sacrificed and testis and epididymis were harvested for further evaluation. The CP-treated group showed significant decreases in the body, testes and epididymis weights and sperm parameters (sperm count, viability, motility) with an increase abnormal sperms when compared with the control (p<0.001), as well as many histological alterations included decreased diameters of seminiferous tubules and Johnsen's Testicular Score (with degeneration, desquamation, multi-nucleated giant cell formation), whereas combined treatment (GV), showed more protective effects on CP-induced reproductive system damage compared with groups III or IV (p<0.001). These results suggest simultaneous administration of Mel and nZno have more effectively protections against CP-induced reproductive damage than Mel or nZno alone.

Effect of Fullerene C60 (NPs) on Cyclophosphamide-Induced Hepato and Cardiac Toxicity in Male Albino Rats.

Background: Toxicity due to drugs used for neoplastic disorders is documented in previous studies. Cyclophosphamide (CP) is a widely used as anticancer drug, which could cause toxicity of normal cells through its toxic metabolites. The fullerene family, especially Fullerene C60 nanoparticles (NPs) can be utilized in many and different biological fields. We evaluated the protective role of Fullerene C60 (NPs) in the toxicity induced by cyclophosphamide. Methods: The activities of serum Liver marker enzymes; alanin amino transferase (ALT) and aspartate amino transeferase (AST), alkaline phosphatase (ALP). T. protein, Albumin, serum heart marker enzymes; Lactate dehydrogenase (LDH) and creatinine phosphokinase (CK) were determined. Results: Toxicity of the organs like heart, and liver was proved from increases of ALT, AST, ALP, LDH and CK values and a decrease in T. protein and Albumin in cyclophosphamide (200 mg/kg a single dose) administered rats, Fullerene C60NPsdissolved in olive oil (0.8 mg/ml) oral treatment will show enhancement against toxicity induced by (CP)at a dose of 4 mg/kg body weight daily for 10 days. Conclusion: In this study, we wish to report that, the in vivo treatment of Fullerene C60 (NPs) was improved the biochemical changes caused by cyclophosphamide-induced toxicities. These results have importance in the fields of medicine. This may open the way for the biomedical applications of C60in treatment of cancer, neurodegenerative disorders, and ageing.

Phytotherapy and phytopharmacology for reduction of cyclophosphamide-induced toxicity in the male urinary system

This systematic review was conducted to evaluate the protective effects and the role of medicinal plants and their derivatives in reducing the cyclophosphamide-induced side effects in the male urinary system. For this systematic review, the search terms cyclophosphamide, urinary system, male reproductive system, toxicity, cancer, chemotherapy, and side effects in combination with the terms medicinal plants, herbal medicines, and natural compounds were used to search for the relevant publications indexed in Google Scholar, Information Sciences Institute, Scopus, and PubMed. Fifteen plant extracts, two essential oils, three plant active components, and two herbal medicines were introduced. According to the results, plants with antioxidant compounds, such as flavonoids, are able to reduce cyclophosphamide-induced testicular toxicity. It is therefore recommended that the plants with significant antioxidant effects be prescribed alongside cyclophosphamide and their effects be compared with other plants plants and their derivatives.

Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats.

The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg(-1) on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg(-1) ) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione-S-transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA-treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.

Cardiorenal protective effect of taurine against cyclophosphamide-induced toxicity in albino rats.

Cyclophosphamide (CP) is a cytotoxic alkylating agent used in the treatment of malignant diseases and autoimmune disorders. Its clinical use is limited to its marked cardiorenal toxicity. The present study aimed to investigate the possible protective role of taurine (Tau; 200 mg·kg-1 per day, i.p.) on CP-induced cardiorenal toxicity. CP (200 mg·kg-1) was administered as a single intraperitoneal injection whereas; Tau was administered for 3 weeks on a daily basis. The results showed that CP produced an elevation in serum activities of creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, creatinine as well as blood urea nitrogen. CP also induced an elevation in the oxidative stress markers viz. elevation in the serum lipid peroxides level (measured as malondialdehyde; MDA) and reduction in reduced glutathione level and superoxide dismutase activity in both heart and renal tissue. On the other hand, administration of Tau attenuated the CP-evoked disturbances in the above mentioned parameters. In addition, CP exhibited electrocardiographic (ECG) changes, which were significantly reversed by Tau treatment. Finally, the histopathological examination emphasized the obtained results. In conclusion, Tau is suggested to be a potential candidate to ameliorate CP-induced cardiorenal toxicity that may be related to its antioxidant activity.

Ameliorative effect of propolis against cyclophosphamide-induced toxicity in mice

Context: Cyclophosphamide (CTX) is a common anticancer agent used for the treatment of several malignancies. However, upon treatment, it induces severe toxicity due to its oxidative stress capability. Propolis, a natural product collected by honey bees, has shown several biological activities, such as free radical scavenging and antioxidant agent.Objective: This study elucidates the protective effects of propolis against CTX-induced changes in mice.Materials and methods: Forty-eight male Swiss albino mice were divided into four groups; group 1 was intraperitoneally (i.p.) injected with 200 µL of phosphate buffer saline (PBS), group 2 was injected with 100 mg/kg/d propolis, group 3 was injected with a single dose of CTX (200 mg/kg), and group 4 was injected with a single dose of CTX (200 mg/kg) followed by propolis (100 mg/kg) for 7 consecutive days. After 12 d, mice were bled and then sacrificed to analyze the hematological, biochemical, and histological parameters.Results: The results indicated that CTX-injected mice showed an increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine and a decrease in the total number of white blood cells (WBCs) and platelets. Moreover, dramatically changes in the histological architectures of the liver and kidney were observed. The mice that were injected with CTX/propolis showed an improvement in the levels of ALT, AST, urea, creatinine, WBCs, and platelets. Moreover, the histological picture of the liver and kidney was significantly improved.Conclusions: In conclusion, propolis might be considered an effective agent in ameliorating the toxicity resulted from CTX treatment.

Abstract 4027: Traditional Chinese Medicine herbal mixture LQ prevents cyclophosphamide-induced metastasis and toxicity

Abstract Cyclophosphamide (CTX) can enhance metastasis (Cancer Res. 66, 303-306, 2006; Cancer Res. 68, 516-520, 2008) and has toxic side effects such as immune-suppression, weight loss, and hair loss. In the present study, the traditional Chinese medicine (TCM) herbal mixture LQ (J. Cell. Biochem. 114, 2131-2137, 2013) was tested to determine if it could enhance CTX efficacy and reduce side effects. HT1080 human fibrosarcoma cells, labeled with GFP in the nucleus and RFP in the cytoplasm, were injected into the epigastric cranialis vein of nude mice that were pre-treated with CTX and LQ. Lewis lung carcinoma (LLC)-RFP cells were injected into the tail vein of mice that were pre-treated with CTX and LQ. Efficacy was monitored with dynamic subcellular imaging of trafficking of cancer cells in blood vessels (Cancer Res. 68, 516-520, 2008) and imaging metastasis to the lung. LQ significantly reduced CTX-induced lung metastasis and cancer-cell adhesion to the inner wall of blood vessels. LQ also reduced kidney toxicity induced by CTX. Treatment with LQ induced hair growth after CTX administration. This result demonstrates that LQ provides safe and effective prevention of metastasis and toxicity in combination with chemotherapeutic agents such as CTX. Citation Format: Lei Zhang, Chengyu Wu, Lingna Li, Yong Zhang, Robert M. Hoffman. Traditional Chinese Medicine herbal mixture LQ prevents cyclophosphamide-induced metastasis and toxicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4027. doi:10.1158/1538-7445.AM2014-4027

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.

Chemoprotective potential of Coccinia indica against cyclophosphamide-induced toxicity.

Objective:Although cyclophosphamide (CP), an alkylating agent, is used in the treatment of cancer owing to its broad-spectrum efficacy, its metabolites exhibit severe undesired toxicities in normal cells. The present study was aimed to investigate the chemoprotective potential of Coccinia indica against CP-induced oxidative stress, genotoxicity, and hepatotoxicity.Materials and Methods:Rodents were orally pre-treated with Coccinia indica extract (200, 400, and 600 mg/kg) for five consecutive days. On 5th day, these animals were injected with CP (50 mg/kg i.p) and sacrificed after 24 hrs. for the evaluation of oxidative stress, hepatotoxicity, micronucleus formation, and chromosomal aberrations.Results:We found that the CP significantly increased malondialdehyde (MDA) and decreased catalase and glutathione (GSH) levels in brain, and it was significantly reversed by Coccinia indica extract (400 and 600 mg/kg). Further, pre-treatment with Coccinia indica extract (200, 400, 600 mg/kg) significantly and dose-dependently reduced micronuclei formation and incidence of aberrant cells. We also found that the CP-induced increase in the serum biomarker enzymes like alkaline phosphatase (ALP), alkaline aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly reduced by Coccinia indica extract.Conclusion:Thus, the present results indicate the protective effect of Coccinia indica extract against CP-induced oxidative stress, genotoxicity, as well as hepatotoxicity.