Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium

Cadmium (Cd) is a potential pollutant of the environment. It manifests cyto-toxic effects in different organs in animals. In the present study, intraperitoneal injection of CdCl(2) (1mg/kg body weight) increased lipid peroxidation in Swiss mice testes indicating oxidative stress during 5th to 8th week of post-treatment .The enzymatic activity of superoxide dismutase (SOD), catalase (CT) and peroxidase (PD) were significantly decreased over the post-treatment phase in Cd-treated mice testes compared to vehicle controls. Further, ascorbic acid content also declined significantly in Cd-exposed mice testes. Following Cd treatment, a marked increase in sperm abnormality percentage and significant decrease in sperm count was observed. The purpose of the present study was to evaluate the effect of vitamins C and E supplementation on Cd-treated mice testes. Therefore, Cd-treated mice groups were injected with vitamins C and E, separately, to assess the effect of the vitamins in combating Cd-induced cytotoxicity and other manifestations. Supplementation of vitamin C (10mg/kg body weight) and vitamin E (100mg/kg body weight) to Cd-induced mice groups declined lipid peroxidation, increased sperm count profile, depressed the percentage of sperm abnormality, increased the activity of antioxidant enzymes mentioned above and also increased the concentration of ascorbic acid to a measurable extent. The role of vitamins in reducing oxidative stress-related effects on spermatogenesis in Cd-treated Swiss mice testes have been reported.     

NTP toxicology and carcinogensis Studies of 2,4-hexadienal (89% trans,trans isomer, CAS No. 142-83-6; 11% cis,trans isomer) (Gavage Studies)

2,4-Hexadienal, a colorless to yellow liquid with a pungent "green" or citrus odor, is used as a food additive for flavor enhancement, as a fragrance agent, as a starting material or intermediate in synthetic reactions in the chemical and pharmaceutical industries, as a fumigant, and as a corrosion inhibitor for steel. 2,4-Hexadienal was nominated for study by the National Cancer Institute because of the potential for carcinogenicity based on its alpha,beta-unsaturated aldehyde structure and the potential link between exposure to lipid peroxidation products in the diet and human malignancies. The commercial product is a mixture containing chiefly trans,trans-2,4-hexadienal in equilibrium with cis,trans-2,4-hexadienal. Male and female F344/N rats and B6C3F1 mice received 2,4-hexadienal (89% trans,trans; 11% cis,trans) in corn oil by gavage for 16 days, 14 weeks, or 2 years. Tissues and plasma from dosed rats were examined for malondialdehyde and glutathione concentrations, and DNA adducts were characterized in liver and forestomach samples from dosed rats and mice. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 3, 9, 27, 80, or 240 mg 2,4-hexadienal/kg body weight in corn oil by gavage, 5 days per week, for 16 days. Three male and three female 240 mg/kg rats died before the end of the study. Mean body weight gains of 240 mg/kg rats were significantly less than those of the vehicle controls. Clinical findings included diarrhea, ataxia, lethargy, and nasal/eye discharge in males, and lethargy, paleness, and abnormal breathing in females in the 240 mg/kg groups. Liver weights of 240 mg/kg females were significantly greater than those of the vehicle controls. Gross and microscopic lesions indicative of forestomach necrosis and ulceration were present in most 240 mg/kg rats, and forestomach epithelial hyperplasia was microscopically evident in most 80 mg/kg rats. 16-DAY STUDY IN MICE: Groups of five male and five female mice were administered 2,4-hexadienal in corn oil by gavage at doses of 0, 3, 9, 27, 80, or 240 mg/kg, 5 days per week, for 16 days. Chemical-related deaths occurred in one male and one female in the 240 mg/kg groups. Female mice in the 240 mg/kg group lost weight during the study. Gross and microscopic lesions indicative of forestomach necrosis and ulceration were present in all 240 mg/kg mice, and forestomach epithelial hyperplasia and hyperkeratosis were microscopically evident in 80 mg/kg mice. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were administered 2,4-hexadienal in corn oil by gavage at doses of 0, 7.5, 15, 30, 60, or 120 mg/kg, 5 days per week, for 14 weeks. All rats survived to the end of the study. Mean body weights of 30, 60, and 120 mg/kg males were significantly less than those of the vehicle controls. The only clinical finding attributed to 2,4-hexadienal administration was hypersalivation in 30 and 120 mg/kg males and females. The incidences of forestomach hyperplasia and nasal olfactory atrophy or necrosis were significantly increased in 120 mg/kg rats. Nasal lesions occurred in most 120 mg/kg male rats. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were administered 2,4-hexadienal in corn oil by gavage at doses of 0, 7.5, 15, 30, 60, or 120 mg/kg, 5 days per week, for 14 weeks. No deaths were attributed to administration of 2,4-hexadienal. Mean body weights of males and females were similar to those of the vehicle controls throughout the study. Clinical findings included salivation and anal wetness in males and females. Kidney weights of 60 and 120 mg/kg males and liver weights of 60 mg/kg males and females were significantly greater than those of the vehicle controls. The incidences of forestomach hyperplasia and/or nasal olfactory atrophy or necrosis were significantly increased in 120 mg/kg mice. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered 2,4-hexministered 2,4-hexadienal in corn oil by gavage at doses of 0, 22.5, 45, or 90 mg/kg, 5 days per week, for up to 105 weeks. Survival of all dosed groups of rats was similar to that of the vehicle control groups. The mean body weights of 90 mg/kg males were generally less than those of the vehicle controls throughout the study. The incidences of squamous cell papilloma of the forestomach occurred with positive trends in male and female rats. This neoplasm was found in 58% of males and 34% of females in the 90 mg/kg groups. In the forestomach of male rats, papilloma multiplicity was increased in the 90 mg/kg group, and squamous cell carcinomas were found in one 45 mg/kg male and two 90 mg/kg males. Epithelial hyperplasia of the forestomach occurred in most 45 and 90 mg/kg rats. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered 2,4-hexadienal in corn oil by gavage at doses of 0, 30, 60, or 120 mg/kg, 5 days per week, for up to 105 weeks. Survival of dosed mice was similar to that of the vehicle controls. The mean body weights of all dosed groups were generally similar to those of the vehicle controls throughout the study. The incidences of squamous cell papilloma of the forestomach occurred with positive trends in male and female mice; squamous cell carcinomas were present in 120 mg/kg males and females. Epithelial hyperplasia of the forestomach occurred in many 120 mg/kg mice. Two 120 mg/kg males had uncommon squamous cell carcinoma of the oral cavity (tongue). GENETIC TOXICOLOGY: 2,4-Hexadienal was mutagenic in S. typhimurium strain TA100 with and without induced hamster or rat liver enzymes; no mutagenic activity was detected with strains TA1535 or TA98, with or without S9. Results of bone marrow tests in male rats and male mice given intraperitoneal injections of 2,4-hexadienal showed a small increase in the induction of micronucleated erythrocytes. However, neither test was repeated, and the test results were judged to be inconclusive. Results of peripheral blood micronucleus tests in male and female mice treated with 2,4-hexadienal by gavage for 14 weeks were negative. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity* of 2,4-hexadienal in male and female F344/N rats and male and female B6C3F1 mice based on increased incidences of squamous cell neoplasms of the forestomach. The occurrence of squamous cell carcinoma of the oral cavity (tongue) in male B6C3F1 mice may have been related to the administration of 2,4-hexadienal. Hyperplasia of the forestomach in male and female rats and mice was associated with administration of 2,4-hexadienal. Synonyms: Hexa-2,4-dienal; 2,4-hexadienal; 2,4-hexadien-1-al; 2,4-Hx; 1,3-pentadiene-1-carboxaldehyde; 2-propylene acrolein; sorbaldehyde; sorbic aldehyde     

The parenteral toxicity of clindamycin 2-phosphate in laboratory animals

The ip and iv LD50 values of 1145 and 855 mg/kg of clindamycin 2-phosphate in the Swiss white mouse were approximately 3 times higher than those of clindamycin hydrochloride. The lesion produced by single injection of 50 or 100 mg/ml of clindamycin 2-phosphate in the loin muscles of the New Zealand White rabbit was graded as slight. The 24-hr serum creatine phosphokinase value was 1500 IU/liter which was less than one-half that of the parent antibiotic.Body weight gains and food conversion ratios in groups of 10 Sprague-Dawley rats injected sc with 120 mg/kg for 6 days were comparable to those of the control group; 90 mg/kg was tolerated in these terms nearly as well for 30 days as no treatment or doses of 30 and 60 mg/kg. From 22 to 33 injections (each equivalent to 30, 60 or 90 mg/kg) were made bilaterally in the posterior thigh muscles of groups of 3 beagle dogs. The terminal elevations of serum glutamic-oxaloacetic transaminase varied from 54 to 400 Reitman-Frankel units. The characteristic pathologic change resulting from the superimposed injections was dose-related progressive scarring of the muscle bundles.Intravenous administration of 60 and 120 mg/kg daily in divided doses in 2 groups of 4 dogs each for 30 days produced no detectable irritation in the peripheral veins or drug-related hemolysis. Tests for drug-induced hemolysis and changes in erythrocyte fragility by in vitro methods were negative. In dogs treated iv with 120 mg/kg for 1 week, as light increase in neutral lipid droplets was present in hepatocytes from 3 hr to 3 days when examined by electron microscopy. This transient change was not observed in dogs injected im with 90 mg/kg for the same period.     

Effects of subchronic ifosfamide-mesna treatment on testes and semen characteristics in the rabbit

Ifosfamide, a chemotherapeutic agent with a broad spectrum of antineoplastic activity, is concurrently administered with the uroprotectant mesna to avoid the urotoxic effect. This study was undertaken to investigate possible effects of ifosfamide-mesna treatment on the testes and semen characteristics in rabbits. Sexually mature New Zealand White male rabbits received intravenously 10 weekly treatments of ifosfamide+mesna (groups A, B and C received 30, 45 or 60 mg/kg of body weight ifosfamide+6, 9 or 12 mg/kg of body weight mesna, respectively, followed by a second equal dose of mesna 4 h later); groups MA, MB and MC received mesna alone at corresponding doses; and group S received normal saline. Reproductive organ weight as well as various qualitative and quantitative parameters of testis histology (minor diameter of seminiferous tubules, the most advanced germ cell type in seminiferous tubule identified in cross sections, and the number of germ cells per stage 1 seminiferous tubule cross section) were determined 1 day and 20 weeks after the treatment period, while semen quality (sperm count, sperm morphology and sperm progressive motility) and libido were evaluated on a weekly basis. Changes were noted only in the ifosfamide+mesna treated animals. One day after treatment, reproductive organ weights were decreased in groups A–C. Major histopathological lesions were not found; however, quantitative histological endpoints were altered in groups A–C. Transient oligospermia and teratozoospermia were noted in groups B and C, while asthenozoospermia was observed in group C only. The time course of these sperm alterations suggested possible bioaccumulation and residual activity of ifosfamide. Libido remained normal. The decrease in reproductive organ weights persisted in groups B and C to 20 weeks after treatment but only one quantitative histological endpoint, the number of the round spermatids per stage 1 seminiferous tubule cross section, remained decreased in group C. These results suggest that subchronic treatment with ifosfamide-mesna suppressed spermatogenesis and epididymal sperm maturation in the rabbit. Germinal epithelium recovery was not complete because although sperm characteristics returned to pretreatment values, not all histological alterations were ameliorated.     

内分泌型隐睾动物模型的建立和比较

目的 通过建立内分泌型隐睾动物模型,改进传统隐睾动物模型的不足,创建一种与临床表现相近可以研究隐睾与不育的关系的动物模型.方法 本实验中使用Sprague-Dawky大鼠,大鼠分为4组:A组(n=28只)内分泌型隐睾组:孕大鼠于孕龄15～17 d注射氟他胺(剂量100 mg/kg)产下的隐睾仔鼠,未出现隐睾的做为药物对照组B组(n=30只)机械法隐睾组:新生期仔鼠切断睾丸引带,将睾丸放入腹腔内结扎鞘膜腔,使睾丸保留在腹腔内.C组(n=15只)药物对照组:经氟他胺处理未出现隐睾的雄鼠.D组(n=30只)正常对照组.上述各组又随机分为3组,分别于30 d、60 d和90 d处死,检查外生殖器和睾丸、附睾的发育情况,称睾丸重量.组织学检查曲细精管直径、Johnson评分和生精上皮计数(CMSE).结果 内分泌型隐睾组32只,其中双侧隐睾4只,单侧隐睾28只.交配实验结果显示:A组受孕实验为阴性,受孕率为60%.B组和D组均为阳性,受孕率为100%.C组有9只受孕实验为阳性,受孕率为90%(P＜0.05).组织学上,隐睾侧睾丸在性成熟后表现为曲细精管直径减小、Johnsen评分下降和生精上皮细胞计数减少、缺少精子.结论 通过对氟他胺诱导的(内分泌型)和传统的手术导致(机械法)2种隐睾动物模型的比较,可以看出内分泌型隐睾动物模型比机械法隐睾动物模型更接近于临床上所出现的隐睾,该模型是一种与临床表现相近可以研究隐睾与不育的关系的动物模型.     

萘普替尼对雄性大鼠睾丸形态结构和附睾精子质量的影响

目的 探究萘普替尼对雄性大鼠睾丸形态结构及附睾精子质量的影响。方法 将30只雄性SD大鼠随机分为30和70 d两组,每组又分为对照组和萘普替尼低、高剂量组（0.75、3.00 mg/kg）,ig给药,每天给药1次,给药体积10 mL/kg。每天进行1次症状观察,每周称量一次体质量,大鼠分别于给药35和70 d后次日处死,肉眼检查各脏器有无异常,检测双侧睾丸质量和横径、附睾尾精子数量和活力,睾丸固定进行组织病理学检查。结果 萘普替尼高剂量组动物均从给药第14天开始,出现腹泻、脱毛、口鼻眼处有红色分泌物,随着给药天数的增加,症状加重;给药70 d组其中1只动物于给药60 d开始出现血尿症状。给药35 d组大鼠从给药21 d开始,给药70 d组从14 d开始,高剂量大鼠体质量明显低于同期对照组（P<0.01）。与对照组比较,给药组雄鼠的双侧睾丸绝对质量和脏器指数、睾丸横径、附睾尾精子数量和活力及睾丸组织病理学检查并未随给药剂量的增加和给药时间的延长而出现明显变化。结论 萘普替尼对雄性大鼠的睾丸组织及精子质量无明显影响。     

The effect of probenecid on acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in the Fischer 344 rat

N-(3,5-Dichlorophenyl)succinimide (NDPS), an experimental agricultural fungicide, has been shown to produce selective nephrotoxicity in rats. Previous studies have shown that a metabolite(s) of extrarenal origin contributes to acute NDPS-induced nephrotoxicity. The purpose of this study was to determine if the organic acid transport inhibitor probenecid could modify the renal toxicity produced by NDPS administration. Male Fischer 344 rats were administered a single intraperitoneal (i.p.) injection of probenecid (60, 90 and 120 mg/kg) or 0.9% saline (1.0 ml/kg) followed 30 min later by NDPS (0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.) Renal function was monitored at 24 h and 48 h. Probenecid (60 mg/kg) did not markedly alter NDPS-induced renal effects on either post-treatment day. However, pretreatment with probenecid (90 or 120 mg/kg) blocked or attenuated the diuresis, increased proteinuria, decreased tetraethylammonium (TEA), uptake, elevation in blood urea nitrogen (BUN) concentration and increased kidney weight produced by NDPS (0.4 mmol/kg) administration. Only increased kidney weight and BUN concentration, and decreased lactate-stimulated p-aminohippurate (PAH) uptake were altered by probenecid (120 mg/kg) pretreatment when NDPS (1.0 mmol/kg) was given. NDPS-induced changes in renal morphology were not prevented by pretreatment with any probenecid dose. These results suggest that at least one nephrotoxic metabolite of NDPS is an organic acid. However, this acidic metabolite might not be the major nephrotoxic metabolite or a precursor to the major nephrotoxic metabolite(s). The identity of these metabolites remains to be determined.     

Evaluation of short-term and subchronic toxicity of magnolia bark extract in rats

Magnolia bark has been traditionally used in Chinese and Japanese medicines, and its extract is a constituent of currently marketed dietary supplements and cosmetic products. The safety of magnolia bark extract (MBE) was assessed in short-term and subchronic studies. In a 21-day pilot study, rats were administered MBE at levels of 0, 60, 120, 240 or 480 mg/kg body weight (bw)/day in the diet. There were no treatment-related effects in clinical observations, macroscopic or microscopic findings, hematological, clinical chemistry, urinalysis, or organ weight measurements, and there were no deaths or significant differences in body weight and weight gain. In the 90-day study, rats were administered 0, 60, 120 or 240 mg MBE/kg bw/day in the diet. No mortality, ophthalmic abnormalities or treatment-related findings in clinical observations, hematology, coagulation or organ weight measurements were observed. There were no treatment-related macroscopic or microscopic findings. Differences between treated and control groups in body weight, weight gain, food consumption and utilization, clinical chemistry and urinalysis parameters were not considered toxicologically significant as they were not dose-related and/or because values remained within historical control ranges. These results support the safety of MBE for oral consumption.     

Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene administered by oral gavage to Sprague-Dawley rats

Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene (DCB) were conducted in male and female Sprague-Dawley rats to meet the needs of the U.S. Environmental Protection Agency for toxicity data on this chemical for use in their determination of possible health risks related to human exposure. 1,2-Dichlorobenzene was administered at doses of 37.5, 75, 150, and 300 mg/kg/day (10-day), and 25, 100, and 400 mg/kg/day (90-day) in corn oil by oral gavage; control animals received corn oil. At time of sacrifice, gross necropsies were performed and selected tissues were weighed and prepared for histological evaluation. Blood was taken for hematology and clinical chemistries. In the 10-day study, exposure of 300 mg DCB/kg body weight to male rats resulted in a statistically significant decrease in final body weight, organ weights (heart, kidneys, spleen, testes, and thymus), and relative organ weights (spleen and thymus). A significant increase in absolute and relative liver weights was also noted in this dose group. Males also displayed significant increases in water consumption (300 mg/kg group), ALT (300 mg/kg) and leukocyte count (150 and 300 mg/kg). A significant increase in the incidence of hepatocellular necrosis was seen in the 300 mg/kg group of males compared to controls. In the 90-day study, male rats exposed to 400 mg DCB/kg displayed a statistically significant decrease in body weight, organ weight (spleen), and relative organ weight (spleen). The absolute weights of kidney and liver and the relative weights for heart, kidney, liver, lung, brain, and testes were increased significantly for this dose group. The absolute and relative weights of both the kidney and liver were significantly increased in the female 400 mg/kg dose group. The only clinical chemistry parameters statistically different than control were increased ALT (100 and 400 mg/kg groups), BUN and total bilirubin in the male 400 mg/kg group and total bilirubin in the 400 mg/kg female group. Histopathological evaluation showed hepatocellular lesions associated with DCB treatment which included centrolobular degeneration and hypertrophy, and single cell necrosis in male and females receiving 400 mg DCB/kg. The NOAEL observed in this study is 25 mg/kg/day.     

Induction of supernumerary ribs with sodium salicylate

Although many chemical agents induce supernumerary ribs (SNR), few efforts have been published examining the induction of SNR in the presence or absence of maternal toxicity and the effect of dose on SNR length. A single administration of sodium salicylate on Day 9 of pregnancy at different dose levels (120, 180, 240, and 300 mg/kg) was used to induce SNR in the thoracolumbar region. At 180, 240, and 300 mg/kg, body weight loss was observed for dams following the administration, associated with reduced food consumption. The mean litter incidence of SNR in the control groups ranged between 0 and 17.1% and in the treated groups (from 180 to 300 mg/kg) between 50.5 and 88.6%. At 120 mg/kg, no adverse effects were noted in dams and the incidence of SNR was in the range of the control groups. Furthermore, in the three highest dose groups, increased incidences of 27 presacral vertebrae (PSV) were noted. In most instances, fetuses with 27 PSV had extra ribs whereas fetuses with 26 PSV tended to have rudimentary ribs. The distinction of SNR between rudimentary and extra ribs is usually based on a ratio of the length of 14th to 13th rib of 0.50. However, this value does not reflect the separation of the apparent bimodal distribution of SNR induced by sodium salicylate. A ratio of 0.35, which corresponds to the superior limit of the SNR of control fetuses, seemed to better define the two populations of SNR.     

Ethylene glycol monomethyl ether effects on health and reproduction in male rabbits

Male Dutch rabbits were weighed and randomly assigned within each weight group to five groups of six animals each (plus one more in the highest dose group). They received 0, 12.5, 25.0, 37.5, or 50.0 mg of ethylene glycol monomethyl ether (EGME) per kg of body weight in the drinking water 5 d/week for 12 weeks. Feed and water consumption were monitored daily and body weight weekly. All animals consumed the water and feed, maintained body weight, and were in good health throughout the experiment. Semen was collected twice weekly for 12 weeks, and 96% of the ejaculates were obtained. By weeks 6 and 9, most males in groups receiving 50.0 or 37.5 mg of EGME per kg were oligospermic. Only minor changes in other characteristics of sperm obtained from treated animals were found, as measured by computer-assisted sperm analysis. Fertility of the males still producing sufficient sperm during week 12 to use for insemination was tested with 96 does producing 2839 oocytes, and fertility of treated males (41%) was not lower (P > 0.05) than 47% in controls. At necropsy, all vital organs were grossly normal, with no notable histopathology. However, the groups of animals receiving 37.5 and 50 mg of EGME per kg of body weight produced fewer sperm and had smaller testes than controls (P < 0.05). Although all rabbits appeared grossly normal, there was a marked disruption of spermatogenesis as ingestion of EGME increased above 25 mg/kg of body weight. Rabbit testes appear to be more sensitive to EGME than testes of rats or mice.     

Evaluation of a testicular sperm head counting technique using rats exposed to dimethoxyethyl phthalate (DMEP), glycerolα-monochlorohydrin (GMCH), epichlorohydrin (ECH), formaldehyde (FA), or methyl methanesulphonate (MMS)

Single dosages of DMEP (1,000–2,000 mg/kg), GMCH (50 mg/kg), ECH (25 and 50 mg/kg), FA (100 and 200 mg/kg), and MMS (100–400 mg/kg) were administered orally to 10 week old male Wistar rats. The rats were necropsied on the 11th day following dosing. The testes were weighed, homogenised and sonicated; numbers of sperm heads (total and abnormal) were counted and percentage sperm head abnormalities were calculated. Testes weights were significantly reduced only in rats exposed to 1,500 and 2,000 mg DMEP/kg. Compared with controls, there were significant increases in the incidence of abnormal sperm at all dose levels of MMS and the higher dose levels of DMEP (1,500 and 2,000 mg/kg), ECH and FA. No texicologically significant effects upon total sperm counts were seen following the oral administration of any of the five chemicals tested. However, an additional group of rats given 100 mg MMS/kg intraperitoneally (i.p.) showed significant reductions in testes weight and total sperm head counts compared with control animals. It is concluded that this testicular sperm head counting technique is a useful tool in the detection of selective adverse effects of chemicals upon testicular sperm but requires further evaluation.     

Short term toxicity study in rats dosed with isoeugenol benzyl ether

Isoeugenol benzyl ether was given to rats by gavage for 28 days at 0, 60, 120, and 240 mg/kg body weight/day. For both sexes at the highest dose and females at the intermediate dose statistically significantly decreased values were found for body weight, blood glucose (also for males at intermediate dose), blood urea and relative liver weights. No dose-related histopathological changes were seen in any organs. The no effect level was 60 mg/kg body weight/day.     

Adipsic,but not anorectic,effect of fluprazine hydrochloride in rats

The present experiment explored the anorectic and adipsic effects of fluprazine hydrochloride, a phenylpiperazine compound. Thirty-eight albino rats were randomly assigned either to a control saline group (six rats) or to groups (eight subjects each) receiving an IP dose of fluprazine in saline (1.25, 2.5, 5 or 10 mg/kg). No anorectic effect of the drug doses was observed 30, 60, 90, 120, 180 and 240 min, and 24 h after drug injection. However, water drinking was significantly decreased 30 min after drug administration, with 5 and 10 mg/kg, compared to saline.     

五步蛇毒抗肿瘤组分X对小鼠生殖毒性及F1子代的影响

目的研究蛇毒的抗肿瘤组分X(FX)对小鼠的生殖毒性及F1子代的影响。方法选状态良好、发育正常的雄性小鼠120只,雌性120只,分别将雌雄小鼠进行随机分组,雄性4组,每组30只,雌性4组,每组30只。给药按照低剂量组为2.5mg/kg;中剂量组为5mg/kg;高剂量组为10mg/kg;第4组为生理盐水阴性对照组(CK),观察对雄鼠、孕鼠一般生殖毒性、围产期生殖毒性的影响。结果低剂量FX对小鼠的一般生殖毒性和围产期生殖毒性影响与对照组比较无显著性差异,高剂量FX对小鼠的一般生殖毒性和围产期生殖毒性影响与对照组比较有显著性差异。结论结果提示5mg/kg剂量用于临床可能是安全的。     

Aluminum-induced suppression of testosterone through nitric oxide production in male mice

Excessive nitric oxide (NO) production in mice serum and testis due to aluminum (Al) exposure has been shown in previous studies. The aim of this study was to further investigate the role of NO on aluminum-suppressed testosterone level in male CD-1 mice. Each animal in six groups, was given intraperitoneal injections of either saline, aluminum chloride (AlCl(3)), l-N(6)-(1-iminoethyl) lysine (NO synthase inhibitor, l-NIL), or Al chloride along with l-NIL for a period of 12 days. These groups were denoted as C (control, saline), AL (35mg Al/kg/day, saline), NIL240 (total 240mg l-NIL/kg, saline), ALNIL240 (35mg Al/kg/day, total 240mg l-NIL/kg), ALNIL60 (35mg Al/kg/day, total 60mg l-NIL/kg), and NIL60 (total 60mg l-NIL/kg, saline). Results indicated that serum/testicular aluminum levels increased significantly in aluminum-treated animals compared to the controls, whereas the values observed from groups ALNIL240 than AL/ALNIL60 were markedly lower. Aluminum administration significantly increased NO production and decreased both testicular adenosine 3',5'-cyclic monophosphate (cAMP) and testosterone levels. A lower level of NO and higher concentrations of cAMP and testosterone observed in the ALNIL240 group indicated that the protective effect of NO synthase blockage was significant, although incomplete. In addition, aluminum induction significantly elevated the testicular cholesterol, but the values were lower in the ALNIL240 group than the AL or the ALNIL60 group. Finally, it was suggested that aluminum compounds exerted a significant adverse effects on the steroidogenesis and cAMP, which aided in the transport of cholesterol to the inner mitochondrial membrane. Furthermore, nitric oxide synthase blockage prevented aluminum-induced reproductive toxicity.     

氟伐他汀对野百合碱所致的大鼠肺血管重塑和右心室肥厚的影响

目的观察氟伐他汀对野百合碱(MCT)所致的大鼠肺血管重塑和右心室肥厚的影响。方法66只大鼠被随机分为3组:(1)M+F组(n=24):本组大鼠首先给予每日1次MCT(60mg/kg)皮下注射,连续2周,第3周至第6周末给予氟伐他汀(1mg/kg)灌胃,每日1次。(2)MCT组(n=24):实验前2周给予每日1次MCT(60mg/kg)皮下注射,第3周至第6周末给予与氟伐他汀等体积的0.9盐水灌胃;(3)Saline组(n=18):分别于实验前2周及第2周末至第6周末给予等体积的0.9盐水皮下注射和灌胃。MCT注射前记为第0周,实验共观察6周。分别于不同时间点观察大鼠肺组织形态学变化,并对平均肺动脉压(mPAP)、管壁厚度百分比(PWT)、右心室肥厚指数(RVHI)进行测定。结果MCT注射2周后,大鼠出现显著的肺血管重塑和右心室肥厚,MCT组大鼠在MCT停止注射后mPAP、PWT及RVHI进一步增高。而M+F组大鼠在给予连续4周氟伐他汀1mg/(kg.d)灌胃处理后,mPAP(23.3±3.2)mmHg及PWT(42.3±2.7)均较MCT组减轻。RVHI(0.32±0.02)亦较MCT组(0.54±0.03)显著降低,且与正常对照组(Saline组)比较无显著差异。结论氟伐他汀能有效减轻MCT诱导的大鼠肺血管重塑和右心室肥厚。     

Subacute toxicity and toxicokinetics of a new antibiotic,DW-224a,after single and 4-week repeated oral administration in dogs

The subacute toxicity and toxicokinetics of a new fluoroquinolone antibiotic, DW-224a, were evaluated after single (on the 1st day) and 4-week (on the 28th day) oral administration of the drug at doses of 0 (to serve as a control), 10, 30, and 90 mg/kg/d, to male and female dogs (n=3 for male and female dogs for each dose). During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathology were examined. The 4-week repeated oral dose of DW-224a resulted in vomiting, salivation, increased serum cholesterol level, and atrophy of thymus and testes. The target organ was determined to be the thymus and testes. The absolute toxic dose of DW-224a was 30 mg/kg and the level at which no adverse effects were observed was 10 mg/kg for both sexes. There were no significant gender differences in the pharmacokinetic parameters of DW-224a for each dose after both single and 4-week oral administration. The pharmacokinetic parameters of DW-224a were dose independent after a single oral administration; the time to reach the peak plasma concentration (T(max)) and the dose-normalized area under the plasma concentration-time curve from time zero to 24 h in plasma (AUC(0-24 h)) were not significantly different among the three doses. The accumulation of DW-224a after 4-week oral administration was not notable at the toxic dose of 90 mg/kg/d. For example, after 4-week administration, the dose-normalized AUC(0-24 h) value at 90 mg/kg/d (7.69, 7.05 microg h/ml) was not significantly greater than that at 10 mg/kg/d. After 4-week oral administration, the dose-normalized C(max) and AUC(0-24 h) at 90 mg/kg/d were not significantly higher and greater, respectively, than those after a single oral administration.     

Effects of diazinon on pseudocholinesterase activity and haematological indices in rats: The protective role of Vitamin E

Diazinon (DZN) is an organophosphate insecticide has been used in agriculture and domestic for several years. Vitamin E (200mg/kg, twice a week), diazinon (10mg/kg, per day) and Vitamin E (200mg/kg, twice a week)+diazinon (10mg/kg, per day) combination were given to rats orally via gavage for 7 weeks. Pseudocholinesterase in serum and haematological indices were investigated at the end of the 1st, 4th and 7th weeks comparatively with control group. At the end of 1st, 4th and 7th weeks, statistically significant decrease of pseudocholinesterase activity in serum were detected when diazinon- and Vitamin E+diazinon-treated groups compared to control group. When diazinon- and Vitamin E+diazinon-treated groups were compared to each other there were no significant changes. When diazinon-treated group was compared to control group, body weight decreased significantly at the end of the 4th and 7th weeks. It was observed that at the end of 1st, 4th and 7th weeks, there was a statistically significance in haematological indices except mean corpuscular hemoglobin (MCH) when diazinon-treated group was compared to control group. At the end of 1st week increase of thrombocyte, at the end of the 4th week increase of hemoglobin and thrombocyte and at the end of the 7th week increase of red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (MCHC) and thrombocyte were observed statistically significant when Vitamin E+diazinon treated group was compared with diazinon treated group. According to the present study, we conclude that Vitamin E reduces diazinon toxicity, but it does not protect completely.     

阿奇霉素对小鼠消化道功能影响的初步研究

目的:研究阿奇霉素对小鼠消化道功能的影响。方法:取小鼠随机分为高、中、低剂量(阿奇霉素240、120、60 mg/kg)实验组和混合组(阿奇霉素240 mg/kg+阿托品1.8 mg/kg)、阴性对照组(0.9%氯化钠注射液),每组20只。除混合组外其余各组小鼠灌胃相应药物,每日1次,连续3 d;混合组小鼠灌胃阿奇霉素第3天时提前30 min灌胃阿托品。末次给药当日测定各组小鼠的体质量、胃排空率和肠推动率,病理学检查胃、肠组织变化。结果:与阴性对照组比较,高剂量实验组小鼠体质量增加减慢、胃排空率和肠推动率均增加,中剂量实验组小鼠肠推动率增加,混合组小鼠体质量增加减慢,差异均具有统计学意义(P<0.05);与混合组比较,中、高剂量实验组小鼠胃排空率和肠推动率均增加,低剂量实验组小鼠肠推动率增加,差异均具有统计学意义(P<0.05),其余各组小鼠指标差异无统计学意义。镜下观察各组小鼠胃、肠组织病理学变化均无明显差异。结论:高剂量阿奇霉素可使小鼠体质量增加减慢,但对胃肠黏膜并无明显刺激,推测其临床引起的消化道反应可能与消化道平滑肌的胆碱受体激活有关。