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Single Intraperitoneal Injection (single + intraperitoneal_injection)
Selected AbstractsLead accumulation in feathers of nestling black-crowned night herons (Nycticorax nycticorax) experimentally treated in the fieldENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2003Nancy H. Golden Abstract Although lead can attain high concentrations in feathers, interpretation of the biological significance of this phenomenon is difficult. As part of an effort to develop and validate noninvasive methods to monitor contaminant exposure in free-ranging birds, lead uptake by feathers of nestling black-crowned night herons (Nycticorax nycticorax) was evaluated in a controlled exposure study. Four- to 6-d-old heron nestlings (one/nest) at Chincoteague Bay, Virginia (USA), received a single intraperitoneal injection of dosing vehicle (control, n = 7) or a dose of lead nitrate in water (0.01, 0.05, or 0.25 mg Pb/g body wt of nestling; n = 6 or 7/dose) chosen to yield feather lead concentrations found at low- to moderately polluted sites. Nestlings were euthanized at 15 d of age. Lead accumulation in feathers was associated with concentrations in bone, kidney, and liver (r = 0.32,0.74, p < 0.02) but exhibited only modest dose dependence. Blood delta-aminolevulinic acid dehydratase activity was inhibited by lead, although effects on other biochemical endpoints were marginal. Tarsus growth rate was inversely related to feather lead concentration. Culmen growth rate was depressed in nestlings treated with the highest dose of lead but not correlated with feather lead concentration. These findings provide evidence that feathers of nestling herons are a sensitive indicator of lead exposure and have potential application for the extrapolation of lead concentrations in other tissues and the estimation of environmental lead exposure in birds. [source] The ameliorative effect of cysteine prodrug l -2-oxothiazolidine-4-carboxylic acid on cisplatin-induced nephrotoxicity in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2007B.H. Ali Abstract Pathogenesis of nephrotoxicity of the synthetic anticancer drug cisplatin (CP) involves generation of reactive oxygen species and free radicals in the kidney cortex, and cysteine prodrug l -2-oxothiazolidine-4-carboxylic acid (OTC) has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of OTC on CP nephrotoxicity in rats. OTC was given at an oral dose of 150 mg/kg/day for 7 days. On day 7, some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg. Rats were killed, blood and urine samples were collected, and the kidneys were removed 6 days after CP treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex, and by urinalyses. CP significantly increased the concentrations of urea and creatinine (P < 0.05) by about 128% and 170% respectively. CP treatment reduced cortical GSH concentration by about 34% (P < 0.05), and the activity of SOD by about 28% (P < 0.05). CP treatment significantly increased urine volume and N -acetyl- , - d -glucosaminidase (NAG) activity, and significantly decreased osmolality and protein concentrations. OTC significantly mitigated all these effects. Sections from saline- and OTC-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This appeared to be lessened when CP was given simultaneously with OTC. The concentration of CP in the cortical tissues was not significantly altered by OTC treatment. The results suggested that OTC had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, OTC may potentially be useful as a nephroprotective agent. [source] Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic painFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2007Sameer Sharma Abstract Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor- , (TNF- ,) and whole brain nitric oxide (NO) release. Four weeks after a single intraperitoneal injection of streptozotocin (STZ, 200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights when compared with control mice. Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF- , levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain. [source] Detoxification and antioxidant effects of curcumin in rats experimentally exposed to mercuryJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2010Rakhi Agarwal Abstract Curcumin, a safe nutritional component and a highly promising natural antioxidant with a wide spectrum of biological functions, has been examined in several metal toxicity studies, but its role in protection against mercury toxicity has not been investigated. Therefore, the detoxification and antioxidant effects of curcumin were examined to determine its prophylactic/therapeutic role in rats experimentally exposed to mercury (in the from of mercuric chloride-HgCl2, 12,µmol,kg,1 b.w. single intraperitoneal injection). Curcumin treatment (80,mg,kg,1 b.w. daily for 3 days, orally) was found to have a protective effect on mercury-induced oxidative stress parameters, namely, lipid peroxidation and glutathione levels and superoxide dismutase, glutathione peroxidase and catalase activities in the liver, kidney and brain. Curcumin treatment was also effective for reversing mercury-induced serum biochemical changes, which are the markers of liver and kidney injury. Mercury concentration in the tissues was also decreased by the pre/post-treatment with curcumin. However, histopathological alterations in the liver and kidney were not reversed by curcumin treatment. Mercury exposure resulted in the induction of metallothionein (MT) mRNA expressions in the liver and kidney. Metallothionein mRNA expression levels were found to decrease after the pre-treatment with curcumin, whereas post-treatment with curcumin further increased MT mRNA expression levels. Our findings suggest that curcumin pretreatment has a protective effect and that curcumin can be used as a therapeutic agent in mercury intoxication. The study indicates that curcumin, an effective antioxidant, may have a protective effect through its routine dietary intake against mercury exposure. [source] In vivo pharmacology and antidiarrheal efficacy of a thiazolidinone CFTR inhibitor in rodentsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2005N.D. Sonawane Abstract A small-molecule inhibitor of the cystic fibrosis transmembrane conductance regulator (CFTR), 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh -172), reduces enterotoxin-induced intestinal fluid secretion in rodents. Here, we study CFTRinh -172 pharmacology and antidiarrheal efficacy in rodents using 14C-labeled CFTRinh -172, liquid chromatography/mass spectrometry, and a closed intestinal loop model of fluid secretion. CFTRinh -172 was cleared primarily by renal glomerular filtration without chemical modification. CFTRinh -172 accumulated in liver within 5 min after intravenous infusion in mice, and was concentrated fivefold in bile over blood. At 30,240 min, CFTRinh -172 was found mainly in liver, intestine, and kidney, with little detectable in the brain, heart, skeletal muscle, or lung. Pharmacokinetic analysis in rats following intravenous bolus infusion showed a distribution volume of 770 mL with redistribution and elimination half-times of 0.14 h and 10.3 h, respectively. CFTRinh -172 was stable in hepatic microsomes. Closed-loop studies in mice indicated that a single intraperitoneal injection of 20 ,g CFTRinh -172 inhibited fluid accumulation at 6 h after cholera toxin by >90% in duodenum and jejunum, ,60% in ileum and <10% in colon. No toxicity was seen after high-dose CFTRinh -172 administration (3 mg/kg/day in two daily doses) in mice over the first 6 weeks of life. The metabolic stability, enterohepatic recirculation, slow renal elimination, and intestinal accumulation of CFTRinh -172 account for its efficacy as an antidiarrheal. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:134,143, 2005 [source] Acute and Chronic Alcohol Exposure Impair the Phagocytosis of Apoptotic Cells and Enhance the Pulmonary Inflammatory ResponseALCOHOLISM, Issue 10 2010Darren M. Boé Background:, Alcohol abuse increases the risk for acute respiratory distress syndrome (ARDS). Efferocytosis, the clearance of apoptotic cells, is important in the resolution of inflammation and is regulated by RhoA and rho kinase (ROCK) activation. The effects of alcohol on pulmonary Rho pathway activation and efferocytosis have not been determined. We hypothesize that acute and chronic alcohol exposure impair pulmonary efferocytosis, leading to heightened inflammation during ARDS. Methods:, For in vivo experiments, C57BL/6 mice received either a single intraperitoneal injection of alcohol or chronic ethanol-in-water for 8 weeks prior to intratracheal instillation of apoptotic cells or lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) was performed for cells counts, calculation of the phagocytic index (PI), and Rho activity measurements. For in vitro studies, primary alveolar macrophages were cultured in alcohol (25,100 mM) and then co-cultured with apoptotic cells. RhoA activity was determined following alcohol exposure, and the PI was determined before and after treatment with the ROCK inhibitor, Y27632. Results:, Acute alcohol exposure was associated with impaired efferocytosis. Following LPS exposure, acute alcohol exposure was also associated with increased BAL neutrophils. Chronic alcohol exposure alone did not alter efferocytosis. However, following exposure to LPS, chronic alcohol exposure was associated with both impaired efferocytosis and increased BAL neutrophils. In vitro alcohol exposure caused a dose-dependent decrease in efferocytosis. Despite the fact that RhoA activity was decreased by alcohol exposure and RhoA inhibition did not alter the effects of alcohol on efferocytosis, treatment with the Rho kinase inhibitor, Y27632, reversed the effects of alcohol on efferocytosis. Conclusions:, Acute alcohol exposure impairs pulmonary efferocytosis, whereas exposure to chronic alcohol is only associated with impaired efferocytosis following LPS-induced lung injury. Both forms of alcohol exposure are associated with increased alveolar neutrophil numbers in response to LPS. The acute effects of alcohol on efferocytosis appear to be mediated, at least in part, by RhoA-independent activation of ROCK. Further studies are needed to dissect the differences between the effects of acute and chronic alcohol exposure on efferocytosis and to determine the effects of alcohol on alternative activators of ROCK. [source] Erythropoietin attenuates white matter damage, proinflammatory cytokine and chemokine induction in developing rat brain after intra-uterine infectionNEUROPATHOLOGY, Issue 5 2009Ying Shen To investigate the possible ameliorating effect of recombinant human erythropoietin (rhEPO) on white matter damage, pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine Escherichia coli infection. E. coli was inoculated into uterine cervix of the time-pregnant rats and the control was injected with normal saline. Following maternal E. coli inoculation, the pups received a single intraperitoneal injection of rhEPO at a dose of 5000 IU/kg body weight immediately after birth. Immunohistochemical staining and Western blot analysis for 2,, 3,-cyclic nucleotide 3,-phosphodiesterase (CNPase), neurofilament (NF) and glial fibrillary acidic protein (GFAP) were performed to assess white matter damage in pup brains at post-natal day 1 (P1), P3 and P7. Pro-inflammatory cytokines and chemokines were detected by real-time quantitative RT-PCR at the mRNA levels to evaluate the inflammatory response in pup brains at P1, P3 and P7. A single dose of rhEPO treatment (5000 IU/kg body weight) attenuated white matter damage in developing rat brain after intra-uterine E. coli infection. The protein levels of CNPase and NF in pup brains at P7 significantly increased after post-natal rhEPO treatment as compared with the intra-uterine E. coli -treated group. Also, post-natal rhEPO injection markedly attenuated the intra-uterine E. coli infection-induced increases in GFAP protein expression and the mRNA levels of pro-inflammatory cytokines and chemokines. Post-natal EPO administration as a single dose may exert a neuroprotective effect on white matter damage by reducing pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine E. coli infection. [source] Time-specific occurrence of alopecia in neonatal C57BL mice treated with N -methyl- N -nitrosourea and the therapeutic efficacy of tacrolimus hydratePATHOLOGY INTERNATIONAL, Issue 3 2000Katsuhiko Yoshizawa Abstract Alopecia was induced in male and female neonatal C57BL mice by a single intraperitoneal injection of 60 mg/kg N -methyl- N -nitrosourea (MNU). MNU administration was most effective in the 8-day-old mice and less effective in the 5-day-old mice (at active and early anagen stages of the first hair cycle, respectively). No alopecia was seen in the day 14 MNU-treated animals (at telogen stage of the first hair cycle). MNU effectively induced hair follicular cell apoptosis at the anagen stage by up-regulation of Bax protein without down-modulation of Bcl-2 protein. In day 8 MNU-treated mice, the immunosuppressive agent 0.01% tacrolimus hydrate (FK506), when topically applied for 5 days from 1 day after MNU treatment (before the occurrence of alopecia), decreased the severity of alopecia. However, it did not stimulate hair growth when applied for 5 days from 20 days of age (after occurrence of alopecia). [source] Inhibitory effect of magnolol on Trp-P-2-induced DNA damage in various organs in micePHYTOTHERAPY RESEARCH, Issue 7 2009Junichiro Saito Abstract Magnolol has been reported to strongly inhibit the mutagenicity induced by indirect mutagens in the Ames test as well as the clastogenicity induced by benzo(a)pyrene (B(a)P) in the mice micronucleus test. Here, we evaluated the inhibitory effect of magnolol on the DNA damage induced by 3-amino-1-methyl-5H -pyrido[4,3-b]indole (Trp-P-2) in various organs using the mice alkaline single cell gel electrophoresis (SCG) assay. Animals were treated with a single oral administration of magnolol (0.01, 0.1, 1, 10, and 100 mg/kg), followed by a single intraperitoneal injection of Trp-P-2 (10 mg/kg). The liver, lung, and kidney were removed at 3 h after treatment and used in SCG assay. The results indicated that magnolol inhibited Trp-P-2-induced DNA damage in various organs. To elucidate the mechanism of this inhibitory effect against Trp-P-2, we investigated the inhibitory effect of magnolol on in vivo CYP1A2 activity using the zoxazolamine paralysis test. Magnolol significantly prolonged zoxazolamine paralysis time and showed an inhibitory effect on in vivo CYP1A2 activity. These results indicate that magnolol has an inhibitory effect on the DNA damage induced by Trp-P-2 in various organs in vivo. This inhibitory mechanism is considered due to in vivo CYP1A2 inhibition. Copyright © 2009 John Wiley & Sons, Ltd. [source] Insulin-Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating DiabetesTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2009Yu-Hua Zhang Abstract Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728,735, 2009. © 2009 Wiley-Liss, Inc. [source] Effect of Withania somnifera on Insulin Sensitivity in Non-Insulin-Dependent Diabetes Mellitus RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Tarique Anwer NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA1c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA1c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index (KITT) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity. [source] A medium-term rat liver bioassay for rapid in vivo detection of carcinogenic potential of chemicalsCANCER SCIENCE, Issue 1 2003Nobuyuki Lto A reliable medium-term bioassay system for rapid detection of carcinogenic potential of chemicals in the human environment has been developed. The 8-week-protocol consists of 2 stages; male F344 rats are given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg) for initiation of liver carcinogenesis, followed by a 6-week test chemical treatment starting 2 weeks thereafter. Test chemicals are usually given in the diet or the drinking water and in the 2nd week of test chemical treatment, all rats are subjected to two-thirds partial hepatectomy in order to induce regenerative cell replication. The end-point marker is the glutathione S-transferase placental form (GST-P)-positive hepatic focus, the numbers and sizes of which are analyzed using an image-analyzer and expressed as values per unit liver section (1 cm2). When the yield of GST-P-positive foci is significantly enhanced (P<0.05) over the control value, a chemical is judged to possess carcinogenic or promotion potential for the liver. Among 313 chemicals already tested in this system in our laboratory, 30/31 (97%) mutagenic hepatocarcinogens and 29/33 (88%) non-mutagenic hepatocarcinogens gave positive results. Ten out of 43 (23%) agents known to be carcinogenic in organs other than the liver were also positive. It is particularly important that only one of 48 non-carcinogens gave a very weak positive result, so that the system has a very low false-positivity rate. It is now well documented that the assay system is highly effective for detecting hepatocarcinogens, bridging the gap between traditional long-term carcinogenicity tests and short-term screening assays. At the Fourth International Conference on Harmonization, our medium-term liver bioassay based on an initiation and promotion protocol was recommended in the guidelines as an acceptable alternative to the long-term rodent carcinogenicity test. (Cancer Sci 2003; 94: 3,8) [source] Decreased Expression of Bcl-x Protein during Hepatocarcinogenesis Induced Exogenously and Endogenously in RatsCANCER SCIENCE, Issue 12 2001Yutaka Hatanaka Dysregulations of apoptosis have been widely recognized as important events in multi-stage carcinogenesis. Bcl-x, a member of the Bcl-2 family, is known to act as a regulator of apoptosis. The present study was conducted to assess the role of altered Bcl-x protein expression in exogenous and endogenous hepatocarcinogenesis in rats. In the short-term exogenous models, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 200 mg/kg body weight, partially hepatectomized at the end of week 3, administered phenobarbital at a concentration of 0.05% from the end of week 2 for 6 weeks, and sacrificed. In the livers, glutathione S-transferase (GST-P)-positive, putative preneoplastic lesions were induced, and Bcl-x protein expression was decreased in 24.7% of such lesions. The incidence of GST-P-positive lesions with decreased Bcl-x increased depending on the size of the lesions; 18.9%, 32.4% and 86.5% in the lesions smaller than 0.03, between 0.03 and 0.3, and larger than 0.3 mm2, respectively. In GST-P-positive lesions larger than 0.3 mm2, both apoptosis induction and cell proliferation activity were enhanced when Bcl-x protein expression was decreased. In the long-term exogenous models, rats were given 10 mg/kg of DEN, partially hepatectomized 4 h after treatment, administered 0.5 mg/kg of colchicine at the end of days 1 and 3, subjected to a selection procedure, and sacrificed at the end of week 45. Hepatocellular carcinomas were induced with the decreased Bcl-x protein expression. In the endogenous model, rats were fed a choline-deficient, l -amino acid-defined diet for 16 or 80 weeks and sacrificed. Bcl-x protein expression was decreased both in GST-P-positive lesions and hepatocellular carcinoma. These results suggest that this decrease of Bcl-x protein might serve as an indicator of the advanced form of preneoplastic lesions, and that this decrease could also be associated with a potential to progress into carcinoma in both exogenous and endogenous hepatocarcinogenesis of rats. [source] Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibodyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2004Y. TAKEDA SUMMARY There is accumulating evidence that haem oxygenase (HO)-1 plays a protective role in various disorders. The beneficial efficacy of HO-1 induction therapy has been shown in renal diseases such as glomerulonephritis, interstitial nephritis and drug induced nephrotoxicity. However, involvement of HO-1 in the development of autoimmune renal diseases remains uncertain. To assess the clinical efficacy of HO-1 induction therapy for lupus glomerulonephritis, MRL/lpr mice were intraperitoneally injected with 100 µmol/kg hemin, a potent HO-1 inducer, or PBS as controls, once a week from 6 weeks of age to 21,24 weeks-old. We found that treatment with hemin led to a significant reduction of proteinuria and remarkable amelioration of glomerular lesions accompanied by decreased immune depositions. In addition, the circulating IgG anti-double-stranded DNA antibody level was significantly decreased in hemin treated mice when compared with controls. A single intraperitoneal injection with hemin resulted in reduction of inducible nitric oxide synthase expression in the kidney and spleen, and serum interferon- , level. Our results suggest that HO-1 induction therapy ameliorates lupus nephritis by suppressing nitric oxide (NO) dependent inflammatory responses and attenuating production of pathogenic autoantibodies. [source] GREEN TEA EXTRACT IMPEDES DYSLIPIDAEMIA AND DEVELOPMENT OF CARDIAC DYSFUNCTION IN STREPTOZOTOCIN-DIABETIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2006PV Anandh Babu SUMMARY 1The efficacy of green tea extract (GTE) on serum and cardiac lipids was investigated in streptozotocin (STZ)-diabetic rats. 2Diabetes was induced in rats by a single intraperitoneal injection of STZ (60 mg/kg bodyweight). Six weeks after the induction of diabetes, GTE was administered orally for 4 weeks (300 mg/kg bodyweight daily). Bodyweight, heart weight, heart weight : bodyweight ratio, blood glucose, serum and cardiac lipids were determined in experimental rats. 3In diabetic rats, there was a significant decrease in bodyweight with an increase in heart weight : bodyweight ratio and blood glucose. Diabetic rats had significantly increased serum levels of cholesterol, triglycerides, free fatty acids and low-density lipoprotein,cholesterol (LDL-C) and decreased levels of high-density lipoprotein,cholesterol (HDL-C). In the hearts of diabetic rats, there was a significant increase in cholesterol, triglycerides and free fatty acids levels, with an increase in lipoprotein lipase activity. 4The administration of GTE to diabetic rats resulted in significant recovery in bodyweight, heart weight : bodyweight ratio and blood glucose levels. The administration of GTE reduced cholesterol, triglyceride, free fatty acid and LDL-C levels, and increased HDL-C levels, in the serum of diabetic rats. In addition, GTE decreased cholesterol, triglyceride, free fatty acids levels and lipoprotein lipase activity in the myocardium of diabetic rats. These beneficial effects of GTE are ascribed to its antihyperglycaemic and hypolipidaemic activity. In conclusion, green tea can reduce the risk of cardiovascular disease in diabetes with a significant improvement in lipid metabolism. [source] Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probeENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2003S.M. Attia Abstract The topoisomerase II (topo II) inhibitors etoposide (VP-16) and merbarone (MER) were investigated with the in vivo micronucleus test (MN test) combined with fluorescence in situ hybridization (FISH) using the mouse minor satellite DNA probe to discriminate MN of clastogenic and aneugenic origin. All experiments were performed with male (102/ElxC3H/El) F1 mice bred in the mouse colony of the GSF Research Center. The sample size per experimental group was five animals and 2,000 polychromatic erythrocytes (PCE) were scored per animal from coded slides in the conventional MN test. A separate set of coded slides was used for the FISH analysis. All treatments consisted of single intraperitoneal injections. Colchicine (COL, 3 mg/kg) and mitomycin (MMC, 1 mg/kg) were used as a positive control aneugen and clastogen, respectively, and these compounds produced the expected responses. A dose of 1 mg/kg VP-16 induced 3.44% MNPCE (compared to the concurrent solvent control of 0.37%, P < 0.001) and of these 39.9% (1.4% MNPCE) showed one or more fluorescent signals. MER (7.5,60 mg/kg) increased the MNPCE frequencies in a dose-dependent manner, with 15 mg/kg being the lowest positive dose. At the highest dose of 60 mg/kg of MER, a total of 4.26% MNPCE were found (compared to 0.31% in the concurrent solvent control, P < 0.001) and of these 46.2% (2.0% MNPCE) contained one or more fluorescent signals. The data demonstrate that VP-16 and MER induced both clastogenic and aneugenic events despite their different modes of topo II inhibition. Environ. Mol. Mutagen. 41:99,103, 2003. © 2003 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||