Protective effects of antioxidants on bitterweed (Hymenoxys odorata DC) toxicity in sheep

Antidotal effects of the 2 antioxidants butylated hydroxyanisole (BHA) and ethoxyquin (EQ) were evaluated in bitterweed (Hymenoxys odorata DC) toxicosis in sheep. Bitteerweed contains a toxic sesquiterpene lactone, hymenoxon, the toxicity of which is reduced by cysteine. Both BHA and EQ are known to induce hepatic glutathione production in rodents. Treatment of sheep with EQ (2.5 g/sheep/day for 9 days before poisoning) gave significant protection from toxic doses of bitterweed, but the protective effect of BHA was insignificant. Of 6 sheep given EQ in the feed, 5 survived 7 doses of bitterweed (4 g/kg/day or higher for 7 days), whereas 5 of 7 controls and 4 of 7 sheep given feed with added BHA died. The added EQ in the feed decreased the serum alkaline phosphatase activity and total protein, albumin, and calcium concentrations. Seemingly, EQ is the first protective agent with field application potential for bitterweed toxicity.     

Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats

Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl-N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22. Necropsy of all rats was performed at week 23, and livers and kidneys were examined histopathologically. Incidences of hepatocellular adenomas, and those of combined hepatocellular adenomas and carcinomas were significantly elevated in rats given 1,000 mg/kg/day ETBE, but not 100‒500 mg/kg/day ETBE, and there was a significant increase in the average numbers of lesions. No significant differences in incidences and average numbers of renal tubule neoplasms were found in rats administered 100‒1,000 mg/kg/day ETBE. However, the average numbers of atypical tubule hyperplasias, considered to be preneoplastic lesions, were significantly increased in rats given ETBE at 1,000 mg/kg/day, but not in rats given 500 mg/kg/day or lower doses. Thus, these results imply that ETBE has hepatic and renal tumor-promoting activities that affect EHEN-induced carcinogenesis in male rats, and the no-observed-effect level is 500 mg/kg/day under the present experimental conditions.     

Neosporosis in cats

Six cats (Nos. 1-6) were inoculated intramuscularly with (1 x 10(6)) and orally (5 x 10(5)) tachyzoites of Neospora caninum. Three (Nos. 1-3) of the six cats were given 40 mg/kg methylprednisolone acetate 7 days before and on the day of inoculation with N. caninum tachyzoites, and three cats (Nos. 4-6) were not given methylprednisolone acetate. Two of the cats (cat Nos. 1 and 2) given methylprednisolone acetate died suddenly. Cat No. 1 died 8 days post-inoculation, and cat No. 2 died 16 days post-inoculation. Cat No. 3 was euthanatized 21 days post-inoculation. Cat No. 1 had lesions of gram-positive bacterial septicemia. Necrotizing encephalitis, myelitis, disseminated skeletal muscle necrosis, hepatic necrosis, interstitial pneumonia, and renal tubular necrosis were the main lesions in cat Nos. 2 and 3. The cats that were not given methylprednisolone acetate remained clinically normal except for slight weight loss in cat No. 6. All three of these cats were euthanatized 55 days post-inoculation. Mild myositis and encephalitis were noted on microscopic examination of tissues from these three cats. Neuromuscular lesions were not seen in six control cats (Nos. 7-12) not inoculated with N. caninum and euthanatized 21 or 22 days after administration of the first two doses of methylprednisolone acetate (40 mg/kg), given at a weekly interval.     

Effects of short courses of different doses of prednisone and dexamethasone on serum third component of complement (C3) levels in dogs.

The effect of different doses of prednisone and dexamethasone on serum C3 levels was determined in 35 dogs. Dogs in Group A (n = 15) were administered prednisone (1.1 mg/kg/day) for 14 days; dogs in Group B (n = 10) were given prednisone at 2.2 mg/kg/day for 7 days; dogs in group C (n = 10) were administered dexamethasone (0.25 g/kg/day) for 7 days. Serum C3 concentrations were determined using a sandwich ELISA in samples obtained before and after glucocorticoid administration. Concentrations were expressed as a percentage of a reference standard. No statistically significant differences were found after glucocorticoid administration in all groups. Thus, short-term administration of prednisone and dexamethasone at commonly used doses did not result in significantly lower serum C3 levels.     

The pathology of experimental Lasiospermum bipinnatum (Thunb.) Druce (Asteraceae) poisoning in sheep. I. Hepatic lesions

Poisoning with the plant Lasiospermum bipinnatum was studied in 9 lambs. Intraruminal doses, varying from 1-12 g/kg/day of dried plant, were administered to 8 animals and 1 was fed 2.5 g/kg/day of the material mixed with maize meal for 13 days. Periodic serum analyses were done to monitor liver function. Lambs given 6-12 g/kg/day died or were killed in extremis. Clinical signs included progressive anorexia and depression in all these lambs and icterus in 2 animals. Lambs given 1-4 g/kg/day were sacrificed after about 2 weeks. Clinical signs in these animals were minimal or absent. Hepatosis was found in all the lambs, the severity of which correlated with levels of plant administered. Centrilobular necrosis and haemorrhage occurred in 2 of the 4 lambs given high doses; single cell necrosis of hepatocytes was observed with intermediate doses, and diffuse degeneration, which was more severe peripherally, was seen at various doses. In 1 lamb, degeneration was most severe midzonally. Bile ductule epithelial proliferation was observed in 7 of the 9 poisoned animals. Marked hypertrophy of hepatocellular smooth endoplasmic reticulum was seen in 3 lambs given low doses. The hepatic lesions were compared with those reported for poisoning by other hepatotoxic plants belonging to the family Asteraceae and found to be indistinguishable.     

Effects of aflatoxins in young ponies

Sixteen clinically normal, healthy ponies were randomly assigned to 4 groups and given aflatoxin B1 in doses of 0.045, 0.030, 0.015, and 0 (control) mg/kg of body weight per day for 21 days (or total doses of 0.945, 0.630, 0.315, and 0 mg/kg). The animals were allowed to recover for 3 months and then were reassigned to 4 treatment groups such that each group during the 2nd trial included a pony from each of the groups of the 1st trial. The animals in the new groups were intubated and were given aflatoxin in doses of 0.4, 0.2, 0.1, and 0 (control) mg/kg/day for 5 days ( or total doses of 2.0, 1.0, 0.5, and 0 mg/kg). Venous blood samples were drawn every other day to monitor for toxicosis; examinations were made for RBC and WBC counts, hemoglobin concentration, PCV, serum urea nitrogen, prothrombin time, and serum concentrations of aspartate aminotransferase, iditol dehydrogenase, alkaline phosphatase, albumin, gamma-glutamyl transferase, and arginase. There were no significant differences between treatment groups and controls (given no aflatoxin) in the toxicologic values examined for during the 1st trial. During the 2nd experiment, 2 of the ponies in the large-dose treatment gorup (2.0 mg/kg) demonstrated increased serum enzyme activities. These animals had been in the large-dose (0.945 mg/kg) and median-dose (0.63 mg/kg) groups during the 1st trial. Arginase, iditol dehydrogenase, and gamma-glutamyl transpeptidase activities became increased on the 4th day of treatment and continued to increase until the 6th day of the experiment (1 day after treatment was terminated). These enzymes approached control group values at 10 days after cessation of treatment. These increases were indicative of hepatocellular toxicity. It was concluded that the possibility of equine aflatoxicosis exists although ponies given high quality rations appear to be less susceptible than some other species. Prior exposure to aflatoxins may predispose to clinical toxicity on subsequent exposure, despite lack of expression of clinical signs.     

Acute experimentally induced aflatoxicosis in the weanling pony

Nineteen weanling ponies and 1 adult pony were given a single oral dose of aflatoxin B1 (AFB1). Dosages were: 0, 0.5, 1, 2, 4, 5, 6, and 7.4 mg of AFB1/kg of body weight. Vital signs were monitored, and whole blood and serum collected for analysis of serum enzymes, prothrombin time, blood cell counts, and serum urea nitrogen. Ponies that died were examined for gross lesions, and tissues were collected for histopathologic examination and analysis of AFB1 and AFM1 residues. Two of the 4 ponies given the 2 mg/kg dose and all ponies given the larger dosages died within 76 hours. Clinical signs included increased rectal temperature, faster heart and respiratory rates, abdominal straining, bloody feces, and tetanic convulsions. At necropsy, ponies that died of acute aflatoxicosis showed visceral petechiae and hepatic focal lesions. Histopathologic changes included severe hepatic necrosis, vacuolation, and bile duct hyperplasia. Aflatoxins B1 and M1 were recovered from liver, kidney, skeletal muscle, and gastrointestinal contents. One other pony given the 2 mg/kg dose died 32 days after dosing, and 1 control pony died after 70 days. Continuous elevations in prothrombin time and serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase levels were observed in ponies dosed at 4 mg/kg or more. Significant (P less than 0.05) elevations in these values, which peaked 2 to 3 days after dosing, were seen in ponies given the 2 mg/kg dose. This group also had significant increases over controls in PCV and hemoglobin concentration 5 days after dosing.     

芩术安胎散的毒性和临床安全性试验研究

试验通过对芩术安胎散的急性毒性、亚慢性毒性和临床安全性进行研究,为芩术安胎散对家猫先兆性流产的预防与治疗提供参考。急性毒性试验：制备芩术安胎散药液,取6周龄健康昆明小白鼠60只,随机分为5组,每组12只,第1~4组的给药剂量分别为6 000、4 800、3 840和3 072 mg/kg,对照组给予等量纯净水,10 d内观察有无中毒和死亡,计算半数致死量（LD₅₀）;另取6周龄健康昆明小白鼠20只,随机分为2组：试验组给予2.0 g/mL芩术安胎散药液,18 h内灌服3次,每次0.8 mL,对照组给予等量纯净水,给药后饲养7 d,计算最大耐受量（MTD）。亚慢性毒性试验：24只7周龄SD雌性大鼠随机均分为高、中、低剂量组和对照组,在30 d内,每日分别给予4 800、2 400和1 200 mg/kg芩术安胎散,对照组以等量纯净水进行灌胃,每日观察和记录各组大鼠的精神状态、有无中毒症状和死亡;第31天对各组大鼠称重、采血,进行血液学检测,剖检各组大鼠,观察主要脏器有无病变并制作病理切片。临床安全性试验：选取2~5岁健康雌性家猫20只,适应性饲养10 d,随机分组,每组5只,分别为低剂量组（1倍临床推荐剂量：1.15 g/kg）、中剂量组（3倍临床推荐剂量：3.45 g/kg）、高剂量组（5倍临床推荐剂量：5.75 g/kg）及空白对照组,将药物置于胶囊内,口服给药,空白对照组给予空胶囊,每日1次,连续给药7 d,每日观察各组家猫食欲、精神状态及排便情况,于第8天对各组家猫进行静脉采血,检测血常规和血液生化指标。结果显示,急性毒性试验无小鼠死亡,LD₅₀>6 000 mg/kg;小鼠对芩术安胎散的最大耐受量为240 g/kg,表明该受试药物无明显毒性。在亚慢性毒性试验中,各组大鼠的生长发育情况、血常规指标、脏器系数与对照组相比均无显著差异（P>0.05）;高、中剂量组与低剂量组、对照组相比血清总胆固醇含量显著下调（P<0.05）,除此之外的生化指标均无显著差异（P>0.05）。病理剖检和组织切片观察结果显示,高剂量组大鼠主要组织器官与对照组相比无明显异常。在临床安全性试验中,不同剂量组家猫精神状态、被毛光泽度、粪便情况均正常,血液学指标与对照组相比差异均不显著（P>0.05）。本试验结果表明,中药芩术安胎散无明显毒性,家猫按临床推荐剂量使用是安全的。     

Adrenocortical suppression in dogs on daily and alternate-day prednisone administration

Three groups of eight normal dogs each were orally given prednisone at doses of 0.22 mg/kg of body weight/day, 0.55 mg/kg/day, or 1.1 mg/kg on alternate mornings. Four dogs served as nontreated controls. Samples were obtained from members of each group to determine baseline serum cortisol and ACTH-stimulated cortisol values and histologic features in the lateral thoracic skin before prednisone administration, and after 1, 2, 3, and 4 weeks of administration. Some animals from each group were necropsied after 1, 2, 3, and 4 weeks of prednisone administration. Each course of prednisone administration resulted in adrenocortical atrophy and hypofunction, but adrenocortical suppression was less severe and slower in onset in the group given prednisone on alternate days. Extra-adrenal effects observed were atrophy of the skin and focal, fatty change of the liver. These changes were most evident in dogs given daily pharmacologic doses of prednisone (0.55 mg/kg/day). Fewer extra-adrenal effects were observed in dogs given alternate-day therapy. There were no extra-adrenal lesions in the dogs given equivalent glucocorticoid replacement doses (0.22 mg/kg/day).     

阿司匹林丁香酚酯对大鼠的急性毒性研究

试验旨在评价阿司匹林丁香酚酯（aspirin eugenol ester,AEE）对大鼠的急性毒性,了解AEE毒性特点及可能的毒性靶器官,并全面地分析大鼠的致死原因。试验按照改良寇氏法进行,预试验选取50只大鼠,雌雄各半,分为5组,测定绝对致死量（LD₁₀₀）和最大非致死量（LD₀）。根据预试验结果,将80只健康大鼠,雌雄各半,随机平均分为7个药物组（剂量分别为2.62、3.25、4.03、5.00、6.20、7.69和9.53 g/kg）和1个对照组（给予0.5%的羧甲基纤维素钠（CMC-Na）进行正式试验。灌胃给药,观察并记录大鼠给药后的临床症状及体重变化。给药14 d后,统计各剂量组大鼠的死亡时间及总死亡数,并计算AEE的半数致死量（LD₅₀）及其95%可信限。同时对死亡大鼠及时进行剖检,将具有病变的组织用10%的甲醛溶液固定,以进行病理学分析。结果显示,AEE对大鼠口服的LD₅₀是5.95 g/kg,且LD₅₀的95%可信限为5.30~6.68 g/kg。对大鼠的死亡时间进行分析可得出,当口服AEE的剂量大于4.03 g/kg时,其死亡时间主要集中在染毒后的48~96 h内。大鼠染毒后3 d内,体重呈下降趋势,常规饲养第5天开始,大鼠体重可逐渐恢复。病理学检查分析发现,AEE的剂量在5.00 g/kg以上时,对大鼠的肝脏、肾脏和胃肠道有明显损伤。根据外源化学物急性毒性分级（WHO）可知,AEE为实际无毒化合物,AEE对大鼠毒性靶器官主要是肝脏、肾脏和胃肠道。     

Acute Toxicity of Aspirin Eugenol Ester on Rats

The acute toxicity study was carried out by intragastric administration in rats to evaluate the toxic characteristics of aspirin eugenol ester (AEE) and target organs and fully analyze the reason of death rats. The experiment was designed in accordance with the method provided by the Kärber arithmetic method. At first, 50 rats (half male and half female)were divided into 5 groups to calculate LD₁₀₀ and LD₀. According to the pre-test results, different doses of AEE (2.62,3.25,4.03,5.00,6.20,7.69 and 9.53 g/kg) and control group of 0.5% CMC-Na were orally administered to 80 rats, half male and half female, divided into 8 groups. After treatment, clinical signs of rats and the change of body weights were observed and recorded. The microscopic pathology of mild damages on organs was conducted. 14 days after adminstration, the death time and total deaths of rats were recorded, and the LD₅₀ and 95% confidence interual of AEE were calculated according to Kärber. Organs were fixed with 10% formaldehyde solution at the end of the experiment. The LD₅₀ of AEE in rats was 5.95 g/kg upon oral administration and its 95% confidence interval calculation was 5.30 to 6.68 g/kg. The death time of rats were centralized at 48 to 96 h after exposing to AEE more than 4.03 g/kg by the analysis of the cumulative mortality-time of AEE in each group. Significant decreases in body weights were noted after treatment of AEE for 3 days, after that body weights gradually grew and recovered at the 5th day. Remarkable damages on livers, kidney and gastrointestinal tract were found at AEE dosage of more than 5.00 g/kg. From the obtained value of LD₅₀>5.00 g/kg, AEE was classified as practically non-toxic compound according to WHO. The target organs of AEE were liver, kidney and gastrointestinal tract.     

Effects of perinatal high dose dexamethasone on skeletal muscle development in rats.

Five litters of suckling rats were given either dexamethasone (DEX), 1 mg/kg, subcutaneously, three times daily (n = 4/litter) or vehicle control (n = 4/litter) from day 3 through day 7 after birth. Rats were weighed weekly and were weaned on day 30. On day 60, rats were killed and the soleus (SOL) and extensor digitorum longus (EDL) were removed for the following analyses: 1) wet weight, 2) light microscopic examination of hematoxylin and eosin stained transverse sections, 3) quantitative morphometric analysis of myosin ATPase stained transverse sections (fiber numbers, fiber type percentages and mean fiber diameters), and 4) DNA (total and mg/g wet weight). The following parameters were significantly reduced in treated rats: 1) body weight, 2) wet weight of SOL and EDL, and 3) mean diameter of SOL type I fibers. There was a trend for total DNA of SOL and EDL to be decreased in treated rats but this was not statistically significant. In a second experiment, pregnant rats (n = 4) were given DEX, 1 mg/kg, subcutaneously, twice daily, on days 17 and 18 of gestation. Two rats served as vehicle controls. The prenatally DEX-exposed rats weighed significantly less on weeks 3, 4, 6, 7 and 8. There were significant reductions in the following parameters for treated rats: 1) SOL wet weight, and 2) total number of SOL type I fibers. There was a trend for SOL DNA to be reduced but this was not statistically significant.     

Spleen-Specific Development of Germinal Centers in Rats Treated with Antithyroid Drugs

The antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) have been used for treatment of hyperthyroidism for more than several decades, despite the fact that they are associated with adverse drug reactions that are thought to be autoimmune mediated. We therefore examined histopathologic responses in the immune system in male and female rats given MMI (2, 20 and 200 mg/kg/day, p.o., in experiment 1; 200 mg/kg/day, p.o., in experiment 3) or PTU (25 and 250 mg/kg/day, p.o., in experiment 2; 200 mg/kg/day, p.o., in experiment 3) for two weeks. In experiments 1 and 2, highest doses of MMI and PTU induced histopathologic changes in the spleen consistent with those in experiment 3 without any changes in the other peripheral lymphoid organs and tissues. In experiment 3, histopathological evaluation of the spleen along with hematological and bone marrow examinations were performed. In both male and female rats, MMI or PTU induced histopathological changes in the spleen characterized by development of germinal centers and an increase in the number of IgG-positive plasma cells in the red pulp; these changes were most prevalent in the MMI-treated female rats. Total red and white blood cell counts were decreased in the MMI-treated male and female rats; lymphocytes and monocytes were lower in male and female rats, respectively. Bone marrow nucleated cells were significantly lower in the MMI-treated males. This is the first study to demonstrate that ATDs induce spleen specific B-cell reactions in rats     

不同剂量链脲佐菌素及不同性别大鼠糖性白内障模型的比较研究

本试验旨在研究不同剂量链脲佐菌素(streptozocin,STZ)及不同性别在建立大鼠糖性白内障模型方面的差异。将65、70和75 mg/kg 3个浓度STZ通过一次性腹腔注射建立雌、雄性大鼠糖性白内障模型,36 h后尾静脉采血测血糖,3周后进行裂隙灯检查,每天测量动物饮食量及排粪尿量变化,每周测定体重。试验结果显示,70 mg/kg STZ比65 mg/kg STZ糖性白内障发生时间缩短约1周,且比75 mg/kg STZ死亡率低。同浓度STZ腹腔注射后雌性大鼠糖尿病发生时间为72 h,雄性大鼠为36 h,白内障发生时间雌性比雄性大鼠慢约1周。试验结果表明,腹腔注射70 mg/kg STZ在糖性白内障模型建立所需时间及模型稳定性等方面具有优势,雄性大鼠较雌性更易于建立糖性白内障模型。     

No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100–1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100–1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses.     

Efficacy of albendazole for prevention of fascioliasis in sheep

Daily doses of albendazole administered as a premix in the feed for 35 days were effective in preventing Fasciola hepatica infections in 17 sheep in three groups: 5 mg/kg/day (6 sheep) was 100% effective; 3 mg/kg/day (5 sheep) was 98% effective; and 1 mg/kg/day (6 sheep) was 42% effective. Infective cysts were given daily for 5 days during the first week of treatment, treatment was continued an additional 28 days, and sheep were necropsied 14 weeks after final cyst inoculation. There were no visible lesions in any livers of sheep given albendazole at the rate of 5 mg/kg/day or in three of five livers of sheep dosed at the rate of 3 mg/kg/day. Sheep treated with albendazole had a mean weight gain of 2.7 kg, 4.0 kg, and 4.0 kg greater than the controls for the dosages of 1, 3, and 5 mg/kg/day, respectively. Determination of bile duct damage by measurement of serum gamma-glutamyl transpeptidase activity at 9 weeks after final cyst inoculation revealed increases of 3.0X, 1.0X, and 1.1X for the dosages of 1, 3, and 5 mg/kg/day, respectively, and 2.3X for the control, as compared with 7 weeks after final cyst inoculation.     

Reduction of carbon tetrachloride-induced hepatotoxic effects by oral administration of betaine in male Han-Wistar rats: a morphometric histological study

Eighty-five male Han-Wistar rats were arranged into three groups: CCl4-exposed rats, CCl4 + betaine-exposed rats, and control rats. To see the effect of betaine alone, five rats of the control and of the CCl4 + betaine groups were sacrificed after 7 days, before exposure to CCl4. After that, two of the groups (the CCl4 and CCl4 + betaine groups) were exposed to CCl4 (1 ml/kg per day subcutaneously [SC] for 4 consecutive days), and one of the groups (control group) was given olive oil (1 ml/kg per day SC for 4 consecutive days). At the start of the study (day 0), day 1, day 2, day 3, day 4, and 3 days after the last CCl4 and olive oil injections (day 7), samples of five rats per group were sacrificed, and the livers were taken for chemical analyses and histological examination. Oral betaine, after the acclimation period of a week, increased the number of mitochondria but not mitochondria size (day 0), compared with the case in control rats. Exposure to CCl4 resulted in centrilobular hepatic steatosis, and the administration of betaine significantly reduced this. Morphometric analyses also revealed that the addition of betaine increased the volume density of rough endoplasmic reticulum (RER) in the perinuclear areas of liver cell cytoplasm (day 7). Additionally, the administration of betaine prevented the reduction of Golgi complexes and mitochondrial figures in the cytoplasm observed after the exposures to CCl4. Also, the volume density of mitochondria was smallest in the CCl4-group, but the difference was not statistically significant. The results indicate that oral betaine either improves recovery or reduces the toxic effects of CCl4 on cell organelles in liver cells of male Han-Wistar rats.     

2-Bromopropane induced germ cell apoptosis during spermatogenesis in male rat

2-Bromopropane (2-BP) causes testicular toxicity in humans and rats. However, the germ cell degeneration of testicular toxicity by 2-BP has not been understood. 2-BP at doses of 135, 405, and 1,355 mg/kg/day was daily injected subcutaneously into Sprague-Dawley rats for 28 days. At the dose of 1,355 mg/kg/day, 2-BP significantly decreased the weights of body and testes, eipididymis, seminal vesicle, and prostate, as well as daily sperm production. Atrophy of seminiferous tubules accompanied with degeneration of germ cells such as spermatogonia, spermatocytes, and elongated spermatids was observed in the testes of rats exposed to the 405 mg/kg/day and 1,355 mg/kg/day of 2-BP. TUNEL-positive germ cells were appeared in the 405 and 1,355 mg/kg/day of 2-BP-treated groups. In addition, ultrastructure alterations of apoptotic germ cells were observed by the electron microscopy study. Dead elongated spermatids were observed at 1,355 mg/kg/day after 28 days exposure. These results suggest that 2-BP impair spermatogenesis may result from apoptotic germ cell death.     

Chronic lead poisoning in horses

Lead acetate was fed to 4 groups of 2 horses each to study chronic lead intoxication. A 5th group of 3 horses was maintained as controls. The leas was fed in capsules, with the minimum dosage of 6.25 mg/kg/day of lead as lead acetate (group I). The dose was increased from group I through group IV in an approximate geometric series, with each group being given about 125% of the dose given the previous group. These doses were given for 105 days, a period designated as phase 1. Since clinical signs were not observed after 105 days, the doses were increased and fed for an additional 190 days (days 106 to 295). This period was designated phase 2. The smallest daily dose in phase 2 was set at about 125% of the largest daily dose in phase 1. The doses in each group was increased by about 125% of that of the previous group, as was done in phase 1. Seven horses died or were euthanatized after 18 to 190 days of phase 2 (123 to 295 days after the 1st dose). One horse in group I did not develop any clinical signs of intoxication. Dose-related responses were unnoticed with doses larger than 15.3 mg/kg/day. All horses given lead had increased blood lead and serum iron concentrations. During phase 2, the hematocrit (erythrocyte volume) and hemoglobin contents were depressed. The lead concentration in kidney, liver, spleen, pancreas, brain, bone, and heart was increased in the treated horses. The dose level required to produce lead intoxication was greater than that reported for cattle and that estimated in epizootiologic studies of horses.     

Effect of zearalenone on early pregnancy in guinea pigs

Female guinea pigs were tested to determine whether they could serve as a model of zearalenone (ZEN) toxicosis during early pregnancy, as observed in domestic swine. Only 1 of 4 female guinea pigs that were given 21 mg of ZEN/kg of body weight orally during the first 8 days after mating was pregnant when examined 22 days after mating. Guinea pigs that were given 7 or 14 mg of ZEN/kg had normal fetal development. Serum concentrations of progesterone were less than 12 ng/ml in all guinea pigs 8 and 15 days after mating. Serum concentrations of progesterone were greater than 100 ng/ml in pregnant guinea pigs on day 22, but remained less than 12 ng/ml in nonpregnant guinea pigs. Three of 5 guinea pigs treated with 20 mg of ZEN/kg and only 1 of 4 guinea pigs given 30 mg of ZEN/kg on days 1 to 3 after mating were pregnant 22 days after mating. Female guinea pigs treated with 20 or 30 mg of ZEN/kg on days 4 to 5 or 6 to 8 after mating and female guinea pigs treated with 60 or 90 mg of ZEN/kg on days 4 and 5 after mating had normal pregnancies. Serum concentrations of progesterone were less than 10 ng/ml in all guinea pigs on day 15 and remained low on day 22 only in nonpregnant guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)