Severe Toxicity (severe + toxicity)

Distribution by Scientific Domains

Selected Abstracts

Weekly 5-fluorouracil plus cisplatin for concurrent chemoradiotherapy in patients with locally advanced head and neck cancer

Young Joo Lee MD
Abstract Background. In locally advanced head and neck cancer, concurrent chemoradiotherapy (CRT) with combined 5-fluorouracil (5-FU) and cisplatin has increased acute toxicities as well as survival. Once-weekly chemotherapeutic administration schedule may reduce severe toxicities. Thus, we investigated CRT using weekly administration of 5-FU,cisplatin in locally advanced head and neck cancer. Methods. In a single-arm, phase II study, CRT included radiation (70.0 Gy/35 fr) and weekly 5-FU (750 mg/m2) and cisplatin (20 mg/m2). Results. Thirty-two patients completed planned radiation. Thirteen (41%) achieved complete response, and 16 (50%) partial response. Twelve patients (38%) experienced acute grade 3 toxicities. Grade 3 mucositis, which was the most common toxicity, developed in 5 (16%) patients. The survival rates at 1 and 2 years were 81% and 76%, respectively. The progression-free survival rates at 1 and 2 years were 69% and 66%, respectively. Conclusions. We demonstrated weekly 5-FU-cisplatin with conventional radiotherapy was efficacious and feasible with high compliance rate in locally advanced head and neck cancer. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source]

Randomized phase 2 study of subcutaneous amifostine versus epoetin-, given 3 times weekly during concurrent chemotherapy and hyperfractionated radiotherapy for limited-disease small cell lung cancer

CANCER, Issue 7 2008
Hye-Suk Han MD
Abstract BACKGROUND. The purpose of the current study was to investigate the role of amifostine and epoetin-, in reducing severe toxicities during concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC). METHODS. Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (Days 1-3) with concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-, at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply. RESULTS. Amifostine treatment was associated with higher febrile neutropenia (P = .003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P = .03). It also demonstrated a trend toward higher grade 4 leukopenia (P = .05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-, (P = .059). Epoetin-, treatment was associated with less grade 2 or 3 anemia (P = .031) and lower decreases in hemoglobin level during CCRT (P = .016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-, arm; P = .447). CONCLUSIONS. Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-, was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated Cancer 2008. © 2008 American Cancer Society. [source]

Bauxite manufacturing residues from Gardanne (France) and Portovesme (Italy) exert different patterns of pollution and toxicity to sea urchin embryos

Giovanni Pagano
Abstract This study was designed to investigate the composition and toxicity of solid residues from bauxite manufacturing plants. Soil and dust samples were collected in the proximity of two bauxite plants (Gardanne, France, and Portovesme, Italy). Samples were analyzed for their content of some selected inorganic contaminants by means of inductively coupled plasma optical emission spectroscopy (ICP-OES) either following acid digestion procedures or by seawater release of soluble components. Toxicity was tested by sea urchin bioassays to evaluate a set of toxicity endpoints including acute embryotoxicity, developmental defects, changes in sperm fertilization success, transmissible damage from sperm to the offspring, and cytogenetic abnormalities. Inorganic analysis showed two distinct sets of inorganic contaminants in Gardanne versus Portovesme, including Al, Cr, Cu, Fe, Mn, Pb, Ti, and Zn; sample composition (seawater-soluble cotaminants) and toxicity showed a noteworthy association. The most severe toxicity to embryogenesis and to sperm fertilization success was exerted by some Portovesme samples (0.03,0.5% w/v), with a significant association between toxicity and dose-related seawater release of Zn, Pb, and Mn. Seawater extraction of a toxic dust sample (G20) from the Gardanne factory showed increasing seawater release of Al, Fe, and Mn; the G20 sample, at the level of 0.5%, affected both developing sea urchin embryos and sperm (offspring quality). Soil samples around the Gardanne factory showed the highest frequency of toxic soil sites eastward from the factory. The present data point to solid deposition from bauxite plants as a potential subject of environmental health concern. The results suggest that extraction methods for evaluating the toxicity of complex mixtures should be based on the environmental availability of mixture components. The differences in sample toxicity among the tested sites, however, suggest possible site-to-site variability in geochemical and/or technological parameters. [source]

Long-lasting infiltration anaesthesia by lidocaine-loaded biodegradable nanoparticles in hydrogel in rats

Background: Infiltration of a long-lasting anaesthetic is helpful during the post-operative period. The recently developed local drug delivery system, biodegradable nanoparticles in a thermo-sensitive hydrogel (nanogel system), may possibly provide an extended duration of drugs. Therefore, we evaluated whether prolonged infiltration anaesthesia could be achieved by loading lidocaine into this delivery system. Methods: Thirty male rats were randomized into five groups of six rats each: saline; 2% hydrochloride lidocaine solution; lidocaine-loaded nanogel system and its compositing formulations, namely lido,nano gel; lido,nano; and lidogel. Durations of local anaesthesia with subcutaneously injected agents were measured by tail flick latency tests in a randomized, blind fashion. Results: Lido,nano gel produced effective anaesthesia for 360±113 min, compared with 150±33 min by lidogel, 180±37 min by lido,nano, and 110±45 min by lidocaine solution (P<0.001, means±SD), and elicited complete sensory blockade for 300±114 min, compared with 75±37 min by lidogel, 105±53 min by lido,nano, and 60±33 min by lidocaine solution (P<0.001, means±SD) without severe skin/systemic toxicity. Conclusion: Lidocaine-loaded biodegradable nanoparticles in hydrogel produced prolonged infiltration anaesthesia in rats without severe toxicity, indicating a possible way to develop long-lasting local anaesthetics. [source]

A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activity

J. Ciccolini PharmD PhD
Summary Background:, Dihydropyrimidine dehydrogenase (DPD) gene polymorphism may lead to severe toxicity with 5-fluorouracil (5-FU), a major anticancer drug extensively used in clinical oncology. Drug monitoring combined with early detection of patients at risk would enable timely dose adaptation so as to maintain drug concentrations within a therapeutic window. However, the best method to identify such patients remains to be determined. Objective:, The aim of this study was to develop a rapid and simple high-performance liquid chromatographic (HPLC) method for estimating uracil/dihydrouracil (U/UH2) ratio in plasma, as an index of DPD status, and for assaying 5-FU as part of drug level monitoring. Method:, Assay of 5-FU, and U/UH2 detection were performed on a HPLC system equipped with UV detector. Analytes were separated at room temperature using a 5 ,m particles, 25 cm RP-18 X-Terra column. The mobile-phase consisted of a KH2PO4 salt solution (0·05 m) + 0·1% triethylamine (TEA) pumped at 0·4 mL/min. Detection of 5-FU and 5-bromouracil were performed at 254 nm; U and UH2 elution was monitored at 210 nm. Results:, The method was sensitive and specific for assaying 5-FU within the 5,500 ng/mL concentration range, which covers exposure levels currently met in clinical practice. The method was simple, and relatively cheap, and rapid, with an analytical run time of about 30 min. Data from a patient with 5-FU toxicity suggest that the method was capable of identifying DPD metabolic phenotype in cancer patients, based on measurement of plasma U/UH2 ratio. Conclusion:, The method described should be suitable both for detecting patients at high risk of 5-FU toxicity, and for drug level monitoring during chemotherapy. [source]

All CVB serotypes and clinical isolates induce irreversible cytopathic effects in primary cardiomyocytes

Jeonghyun Ahn
Abstract Coxsackievirus B3 (CVB3) has been identified as a major causative agent of acute and chronic myocarditis, but the involvement of other CVB serotypes in myocarditis has not been investigated. To dissect the pathological properties of different CVB serotypes toward primary cardiomyocytes, we tested their effects on primary cardiomyocyte cultures from neonatal rats. Morphological abnormalities were examined by both light and fluorescence microscopy after Hoechst 33342 staining, and loss of cell viability was estimated by MTT assay. All six CVB serotypes showed a similar degree of severe toxicity toward primary cardiomyocytes. CVB clinical isolates had cytopathic effects (CPEs) similar to those of their respective CVB reference strains. Within 1,2 days of infection with multiplicities of infection MOI 50, the cells began to experience morphological changes including cell shrinkage, rounding-up, and slight nuclear condensation. The irreversible loss of cell viability was readily observed within 3,5 days following virus infection. These results suggest that all six CVB serotypes induce direct, irreversible toxicity towards cardiomyocytes, which eventually leads to the death of infected cells. These findings indicate that the variations in CVB serotype are not the limiting factor determining the susceptibility of cardiomyocytes to CVB infection. J. Med. Virol. 75:290,294, 2005. © 2004 Wiley-Liss, Inc. [source]

Intra-arterial therapy with cisplatin suspension in lipiodol and 5-fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis

H. Nagamatsu
Aliment Pharmacol Ther 2010; 32: 543,550 Summary Background, Portal vein tumour thrombosis is a negative prognostic factor for hepatocellular carcinoma (HCC). Aim, To assess the efficacy of cisplatin in lipiodol emulsion combined with 5-fluorouracil (5-FU) for patients with HCC and portal vein tumour thrombosis. Methods, The study subjects were 51 patients with the above-specified criteria who received injection of cisplatin suspension in lipiodol emulsion followed by intra-arterial infusion of 5-FU. The primary objective was to determine tumour response to the treatment, while the secondary objectives were safety and tolerability. Independent factors for survival were also assessed. Results, Ten patients had complete response and 34 patients had partial response (response rate, 86.3%). The median survival for all 51 patients was 33 months, while that for 10 complete response patients and 21 patients who showed disappearance of HCC following additional therapies was 39 months. The single factor that significantly influenced survival was therapeutic effect. Treatment was well tolerated and severe toxicity was infrequent, with only grade 3 toxicity (thrombocytopenia) in one patient. Conclusions, The present study demonstrated the efficacy of hepatic arterial infusion chemotherapy using cisplatin-lipiodol emulsion and 5-FU without serious adverse effects in patients with unresectable HCC and portal vein tumour thrombosis. [source]

Phase I Dose Escalation of Single-Agent Vinblastine in Dogs

D.B. Bailey
Background: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. Hypothesis: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. Animals: Twenty-three dogs with lymphoma or cutaneous mast cell tumors. Methods: Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2,3 weeks. Results: VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. Conclusions and Clinical Importance: In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered. [source]

Danazol therapy for aplastic anemia refractory to immunosuppressive therapy

Tatsuya Chuhjo
Although there are anecdotal reports of the efficacy of danazol in the treatment of aplastic anemia (AA), there has been no systematic study to clarify its efficacy and toxicity. Therefore, we assessed the efficacy of danazol for treatment of patients with AA refractory to immunosuppressive therapy (IST) and those who relapsed after IST, in a prospective clinical trial. Sixteen patients (12 males and four females; six severe cases and 10 moderate cases) were treated with 300 mg of danazol daily for 12 weeks. All patients completed the treatment period without occurrence of severe toxicity. Three female patients achieved partial remission, whereas only two of the 12 male patients did so. None of the responders had shown a response to previous IST or an increase in the percentage of paroxysmal nocturnal hemoglobinuria (PNH)-type cells which are known to be a marker for a good response to IST. These findings indicate that danazol is effective for a subset of AA patients, and particularly for female patients with AA refractory to IST. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc. [source]

The low frequency of defective TPMT alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia,

Tugba Boyunegmez Tumer
6-Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP. Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C, are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPMT*3A and TPMT*3C were the only deficiency alleles detected in Turkish population with an allele frequency of 0.9% for both. While *3C allele frequency in Turkish population was found to be very similar to Asian and other Caucasian populations, *3A allele frequency was significantly (P < 0.05) lower. So far, studies showed that the genetic polymorphisms of other drug metabolizing enzymes like CYP2E1, CYP1A1, GSTM1/ T1 in Turkish population were similar to Caucasian populations. However, we found that the distribution of TPMT polymorphisms in Turkish population was significantly lower than those in other Caucasians like British, French, and Italian whereas the distributions of TPMT variants were found to be very similar to Kazak population which is also Caucasian in ethnic origin. In this study, the clinical histories of the patients in the sample population were also examined, retrospectively. The patients with heterozygous or homozygous mutant genotypes had developed severe neutropenia and infection during 6MP therapy. The study provides the first data on the frequency of common TPMT variants in the Turkish population, based on analysis of pediatric patients with ALL. Am. J. Hematol. 82:906,910, 2007. © 2007 Wiley-Liss, Inc. [source]

Chlorpromazine and apigenin reduce adenovirus replication and decrease replication associated toxicity

Anna Kanerva
Abstract Background Adenoviruses can cause severe toxicity in immunocompromised individuals. Although clinical trials have confirmed the potency and safety of selectively oncolytic adenoviruses for treatment of advanced cancers, increasingly effective agents could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. Methods We analyzed the effect of chlorpromazine, an inhibitor of clathrin-dependent endocytosis and apigenin, a cell cycle regulator, on adenovirus replication and toxicity. First, we evaluated the in vitro replication of a tumor targeted Rb-p16 pathway selective oncolytic adenovirus (Ad5/3-,24) and a wild-type adenovirus in normal cells, fresh liver samples and in ovarian cancer cell lines. Further, we analyzed the in vitro cell killing efficacy of adenoviruses in the presence and absence of the substances. Moreover, the effect on in vivo efficacy, replication and liver toxicity of the adenoviruses was evaluated. Results We demonstrate in vitro and in vivo reduction of adenovirus replication and associated toxicity with chlorpromazine and apigenin. Effective doses were well within what would be predicted safe in humans. Conclusions Chlorpromazine and apigenin might reduce the replication of adenovirus, which could provide a safety switch in case replication-associated side effects are encountered in patients. In addition, these substances could be useful for the treatment of systemic adenoviral infections in immunosuppressed patients. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Utility-Based Optimization of Combination Therapy Using Ordinal Toxicity and Efficacy in Phase I/II Trials

BIOMETRICS, Issue 2 2010
Nadine Houede
Summary An outcome-adaptive Bayesian design is proposed for choosing the optimal dose pair of a chemotherapeutic agent and a biological agent used in combination in a phase I/II clinical trial. Patient outcome is characterized as a vector of two ordinal variables accounting for toxicity and treatment efficacy. A generalization of the Aranda-Ordaz model (1981,,Biometrika,68, 357,363) is used for the marginal outcome probabilities as functions of a dose pair, and a Gaussian copula is assumed to obtain joint distributions. Numerical utilities of all elementary patient outcomes, allowing the possibility that efficacy is inevaluable due to severe toxicity, are obtained using an elicitation method aimed to establish consensus among the physicians planning the trial. For each successive patient cohort, a dose pair is chosen to maximize the posterior mean utility. The method is illustrated by a trial in bladder cancer, including simulation studies of the method's sensitivity to prior parameters, the numerical utilities, correlation between the outcomes, sample size, cohort size, and starting dose pair. [source]

A randomized study of docetaxel and dexamethasone with low- or high-dose estramustine for patients with advanced hormone-refractory prostate cancer

OBJECTIVE To test the combination of docetaxel with two different doses of estramustine in patients with hormone-refractory prostate cancer (HRPC), to improve response rates and to lower side-effects, as docetaxel-based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival. PATIENTS AND METHODS In all, 72 patients with metastatic HRPC were randomly assigned to receive docetaxel (70 mg/m2 intravenously, on day 2 every 21 days) and estramustine (3 × 280 mg/day oral starting 1 day before docetaxel, for 5 consecutive days) for arm A, or estramustine (3 × 140 mg/day oral starting 1 day before docetaxel, for 3 consecutive days) for arm B. Premedication with oral dexamethasone at a total daily dose of 16 mg, in divided doses twice a day was administered in arm A on day 1,5 and in arm B on day 1,3. Initially, six cycles were administered. Chemotherapy was restarted after a significant increase in prostate-specific antigen (PSA) level. Patients were monitored for any measurable PSA response and toxicity. RESULTS Between the arms there was no statistically significant difference in time to progression and overall survival. However, treatment B had less treatment-related toxicity than A. Independent prognostic variables were baseline factors like PSA level, haemoglobin level, Eastern Cooperative Oncology Group performance status, and bone pain at presentation. CONCLUSIONS In this randomized phase II study the combination of docetaxel and estramustine had substantial activity in HRPC, with a significant incidence of severe toxicity, both haematological and not. Nevertheless, treatment-related toxicity was predictable and manageable. There was no better effect with a higher dose of estramustine with docetaxel than for a lower dose. There was a slight tendency to higher toxicity for high-dose estramustine but this was not statistically significant. The present results support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. [source]

Absence of large intragenic rearrangements in the DPYD gene in a large cohort of colorectal cancer patients treated with 5-FU-based chemotherapy

Laia Paré
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Dihydropyrimidine dehydrogenase (DPD) is the enzyme responsible for the elimination of approximately 80% of the administered dose of 5-fluorouracil (5-FU). , Mutations in the DPD-coding gene have been shown to increase the risk of severe toxicity in 5-FU treated patients. , The IVS14+1G>A is the most common DPYD mutation. WHAT THIS STUDY ADDS , The intragenic rearrangements of DPYD using multiplex ligation-dependent probe amplification (MLPA) were studied for the first time in a large series of 234 colorectal cancer patients treated with 5-FU-containing chemotherapy. , No deletions or duplications of one or more DPYD exons were detected. The presence of the IVS14+1G>A mutation was also excluded. , These data show that neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation are responsible for the serious toxicity associated with a 5-FU containing regimen in this cohort of Spanish patients. AIMS To study the relationship between the toxicity associated with a 5-FU-based therapy and the presence of (i) the large intragenic rearrangements in the DPYD gene and (ii) the IVS14+1G>A mutation. METHODS We used the multiplex ligation-dependent probe amplification technique (MLPA) to study genomic DNA from 234 colorectal cancer patients treated with 5-FU-based chemotherapy. RESULTS We did not detect any deletion/duplication in the DPYD gene. The presence of the IVS14+1G>A mutation was also excluded. CONCLUSIONS Neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation play a significant role in the development of serious toxicity associated with a 5-FU containing regimen. [source]

Toxicity of radiotherapy in patients with collagen vascular disease

CANCER, Issue 3 2008
Alexander Lin MD
Abstract BACKGROUND. A diagnosis of collagen vascular disease (CVD) may predispose to radiotherapy (RT) toxicity. The objective of the current study was to identify factors that influence RT toxicity in the setting of CVD. METHODS. A total of 86 RT courses for 73 patients with CVD were delivered between 1985 and 2005. CVD subtypes include rheumatoid arthritis (RA; 33 patients), systemic lupus erythematosus (SLE; 13 patients), scleroderma (9 patients), dermatomyositis/polymyositis (5 patients), ankylosing spondylitis (4 patients), polymyalgia rheumatica/temporal arteritis (4 patients), Wegener granulomatosis (3 patients), and mixed connective tissue disorders (MCTD)/other (2 patients). Each patient with CVD was matched to 1 to 3 controls with respect to sex, race, site irradiated, RT dose (±2 Gray), and age (±5 years). RESULTS. There was no significant difference between CVD patients (65.1%) and controls (72.5%) experiencing any acute toxicity. CVD patients had a higher incidence of any late toxicity (29.1% vs 14%; P = .001), and a trend toward an increased rate of severe late toxicity (9.3% vs 3.7%; P = .079). RT delivered to the breast had increased risk of severe acute toxicity, whereas RT to the pelvis had increased risk of severe acute and late toxicity. RT administered in the setting of scleroderma carried a higher risk of severe late toxicity, whereas RT to SLE patients carried a higher risk of severe acute and late toxicity. CONCLUSIONS. Although generally well tolerated, RT in the setting of CVD appears to carry a higher risk of late toxicity. RT to the pelvis or in the setting of SLE or scleroderma may predispose to an even greater risk of severe toxicity. These issues should be considered when deciding whether to offer RT for these patients. Cancer 2008. © 2008 American Cancer Society. [source]

Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract

F. V. Pinheiro
Abstract The methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. The present study was undertaken to determine whether Grape seed (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative injury and the effect on adenosine deaminase activity (ADA) in rats. The rats were pretreated with 50,mg/kg of GSE, i.p., prior to MTX administration (10,mg/kg, i.p.) with a second dose given 4,h and a third dose 16,h after MTX administration. Biochemical parameters were investigated 48,h after the last MTX administration. The administration of MTX increased thiobarbituric acid reactive species (TBARS) levels in hippocampus, kidney and liver, whereas induced a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. MTX administration significantly increased the activity of ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in the serum. Urinary uric acid levels decreased in the MTX group when compared to those of the control group. The GSE along with MTX-administration significantly reversed these parameters toward to near normal. These results indicated that GSE could reduce hepatic and nephritic damage induced by MTX-treatment in young rats therefore having free radical scavenging. Copyright © 2009 John Wiley & Sons, Ltd. [source]