Pathology of 2-alkyl and 2-hydroxy naphthoquinone toxicity in rats

Abstract Extract The oral administration of 2-methyl-1, 4-naphthoquinone (menadione) to rats caused oxidative destruction of the erythrocyte. Heinz body formation occurred in erythrocytes, lowered PCVs and haemoglobin Occurred in blood, with splenic and hepatic erythroclasis, and iron conservation in the spleen, liver and kidney. These effects diminished when increasingly large alkyl substitutions of the methyl group of thi naphthoquinone were made. No effect was caused by the 2-decyl derivative.     

Pathology and histopathology of gossypol toxicity in broiler chicks

Two experiments were conducted to determine the toxicity, pathology, and histopathology of purified gossypol in broiler chicks. Gossypol was added to broiler feed at 0, 100, 200, and 400 mg/kg of feed in Experiment 1 and at 0, 800, and 1600 mg/kg of feed in Experiment 2. Day-old broiler chicks were fed these diets from 1 to 21 days in Experiment 1 and from 1 to 23 days in Experiment 2. In Experiment 1, body weight and feed intake at 21 days were not significantly affected by dietary gossypol. However, chicks fed gossypol at 400 mg/kg of feed had poor feed conversion ratio compared with the other treatment. Feed conversion ratios were 1.493, 1.564, 1.471, and 1.60 for chicks fed gossypol at 0, 100, 200, and 400 mg/kg of feed, respectively (Experiment 1). Chicks fed 400 mg/kg gossypol also had mild perivascular lymphoid aggregate formations and bilary hyperplasia in the liver. In Experiment 2, gossypol at 1600 mg/kg resulted in 28.1% mortality. Gossypol at 800 and 1600 mg/kg feed resulted in significant decreases in body weight and feed intake of chicks. The average body weights of 23-day-old chicks in Experiment 2 were 676, 224, and 111 g for 0, 800, and 1600 mg/kg gossypol, respectively. Feed conversion ratios of chicks fed 800 and 1600 mg/kg gossypol were significantly higher than those of chicks fed control diets (1.383 vs. 1.564 vs. 1.745 for 0, 800, and 1600 mg/kg gossypol, respectively). Plasma iron and hematocrit values were significantly reduced by gossypol at 800 and 1600 mg/kg of feed. Enlarged gallbladder was the only gross pathology symptom associated with gossypol levels. Severe cases of perivascular lymphoid aggregate formation, biliary hyperplasia, and hepatic cholestasis were observed in chicks fed 800 and 1600 mg/kg of gossypol in feed. No gossypol-related changes were observed in kidney tissues of chicks. These results show that gossypol is toxic to broiler chicks at high levels. This study also shows that histopathologic changes in liver due to gossypol also occur at levels lower than the levels that affect body weight.     

实验性雏鸭锌中毒症的病理学研究

1日龄天府肉鸭健雏100只随机分为2组，分别喂以止常对照(Zn100mg／kg日粮)和锌中毒(Zn1300mg／kg日粮)日粮4周，进行系统的病理学研究。中毒鸭13d出现症状，18只死亡。尸检主要见腿部肌肉色白或灰白色，外观似蜡样；肌胃平滑肌色淡灰白；消化道充满黑褐色煤焦油样内容物。光镜下，骨骼肌纤维肿胀变性坏死；心肌和肌胃平滑肌局灶性坏死；胸腺、腔上囊、脾脏淋巴细胞减少。电镜观察，免疫器官淋巴细胞线粒体肿胀、嵴断裂。血液病理学变化主要是碱性磷酸酶活性、血清总蛋白与球蛋白含量以及红细胞总数和血红蛋白含量降低，血清谷丙转氨酶活性和锌含量升高。结果表明，高锌对鸭可产生明显的毒害作用。文中还对发病机理进行了探讨。     

Pathology of acute 3-acetyldeoxynivalenol toxicity in mice.

Mice were killed 2, 4, 6, 12, 24, 48 and 96 hours after intragastrical administration of 0, 5, 10, 20, or 40 mg/kg body weight of 3-acetyldeoxynivalenol. The animals became clinically ill after 12 hours and some animals in the highest dose group died. Histological examination of duodenal crypts, thymus and spleen revealed, in all dose groups, presence of the characteristic lesions that are known to be produced by trichothecenes, but the intensity of lesions in the 40 mg group corresponded to lesions known to be caused by 4 mg/kg of T-2 toxin. A rabbit skin bioassay with 3-acetyldeoxynivalenol gave negative results on one occasion and a mild reaction to 100 to 500 micrograms/mL on another. It is concluded that 3-acetyldeoxynivalenol is considerably less toxic than T-2 toxin, but causes acute effects in the dividing cells of the body in a manner characteristic of trichothecenes.     

Luteal toxicity evaluation in rats

The corpora lutea (CL) are endocrine glands that form in the ovary after ovulation and secrete the steroid hormone, progesterone (P4). P4 plays a critical role in estrous and menstrual cycles, implantation, and pregnancy. The incomplete rodent estrous cycle stably lasts 4–5 days and its morphological features can be distinguished during each estrous cycle stage. In rat ovaries, there are two main types of CL: newly formed ones due to the current ovulation (new CL), and CL remaining from prior estrous cycles (old CL). In the luteal regression process, CL were almost fully regressed after four estrous cycles in Sprague-Dawley rats. P4 secretion from CL in rodents is regulated by the balance between synthesis and catabolism. In general, luteal toxicity should be evaluated by considering antemortem and postmortem data. Daily vaginal smear observations provided useful information on luteal toxicity. In histopathological examinations, not only the ovaries and CL but also other related tissues and organs including the uterus, vagina, mammary gland, and adrenal glands, must be carefully examined for exploring luteal changes. In this review, histological and functional characteristics of CL in rats are summarized, and representative luteal toxicity changes are presented for improved luteal toxicity evaluation in preclinical toxicity research.     

Pathology of domoic acid toxicity in California sea lions (Zalophus californianus)

Over 100 free-ranging adult California sea lions (Zalophus californianus) and one Northern fur seal (Callorhinus ursinus), predominantly adult females, were intoxicated by domoic acid (DA) during three harmful algal blooms between 1998 and 2000 in central and northern California coastal waters. The vector prey item was Northern anchovy (Engraulis mordax) and the primary DA-producing algal diatom was Psuedonitzschia australis. Postmortem examination revealed gross and histologic findings that were distinctive and aided in diagnosis. A total of 109 sea lions were examined, dying between 1 day and 10 months after admission to a marine mammal rehabilitation center. Persistent seizures with obtundation were the main clinical findings. Frequent gross findings in animals dying acutely consisted of piriform lobe malacia, myocardial pallor, bronchopneumonia, and complications related to pregnancy. Gross findings in animals dying months after intoxication included bilateral hippocampal atrophy. Histologic observations implicated limbic system seizure injury consistent with excitotoxin exposure. Peracutely, there was microvesicular hydropic degeneration within the neuropil of the hippocampus, amygdala, pyriform lobe, and other limbic structures. Acutely, there was ischemic neuronal necrosis, particularly apparent in the granular cells of the dentate gyrus and the pyramidal cells within the hippocampus cornu ammonis (CA) sectors CA4, CA3, and CA1. Dentate granular cell necrosis has not been reported in human or experimental animal DA toxicity and may be unique to sea lions. Chronically, there was gliosis, mild nonsuppurative inflammation, and loss of laminar organization in affected areas.     

Comparison of gentamicin toxicity in normal and diabetic rats.

Gentamicin treatment caused an elevation in serum urea and creatinine concentrations and ALT activity, associated with pathological changes in the liver and kidney. The pathological and blood chemistry changes were more severe in diabetic gentamicin-treated than in non-diabetic gentamicin-treated rats. Alloxan-diabetic rats had lowered blood glutathione concentrations which may have been responsible for the enhancement of gentamicin toxicity in these rats.     

Pathology of GM2 gangliosidosis in Jacob sheep

The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model.     

微胶囊化儿茶素的慢性毒性试验研究

儿茶素是从茶叶中提取的多酚基次生代谢物,具有抗氧化、降血脂、抗动脉粥样硬化、抗衰老、抑制癌细胞等多种功能,但儿茶素在非保护状态下生物利用率不高,利用微胶囊化儿茶素可提高儿茶素的生物学效应.为了给微胶囊化儿茶素的临床安全利用提供依据,笔者等观察了微胶囊化儿茶素的慢性毒理学特性.现将结果报告如下.     

Concentration-time interactions in hydrogen sulphide toxicity in rats.

Concentration-time interactions were investigated in young male and female Sprague-Dawley, Long Evans and Fischer-344 rats exposed to hydrogen sulphide for two, four or six hours. Higher concentrations caused more deaths, with no significant difference for duration of exposure. A significant sex effect was noted with 30% mortality in males and 20% in females, with no significant difference among strains. Changes in weight were significant: increasing with concentration, higher in males than in females, different among strains (Fischer-344 less than Sprague Dawley less than Long Evans), and affected by duration of exposure. Lethal concentration values (LC50 and LC10) were estimated, for the pooled data set (n = 456); the probit equation was Y = -5.74749 + 3.8259X where X is log10 dose of hydrogen sulphide in parts per million. The LC50/LC10 values were 644/298 parts per million (902/417 mg m-3) respectively. Individual probit analyses were also performed for strain, hours of exposure and sex. The LC50 and LC10 values for male, female and strain were not different. Significant differences were observed among LC50/LC10 values for hours of exposure (2 h = 587/549 parts per million, 822/769 mg m-3; 4 h = 501/422 parts per million, 701/591 mg m-3; 6 h = 335/299 parts per million, 469/491 mg m-3). There was no effect of spatial position in the exposure chamber on the distribution of mortality. All rats of all strains dying had severe pulmonary edema.     

Evaluation of bone toxicity in various bones of aged rats

The aim of the present study was to provide a method for evaluating bone toxicity induced by drugs in various bones in aged rats. Male Crl:CD (SD) rats at 46 weeks of age were administered 15 mg/m(2) body surface area of doxorubicin, which effects the growth plate in weanling rats, weekly for 9 weeks by intravenous injection, and the femur, sternum, humerus and tibia were examined histopathologically. In the doxorubicin-treated group, thinning of the growth plate was remarkably observed in the proximal tibia and humerus; however, these changes were not observed in other regions. In addition, the osteoclast number per bone perimeter in the proximal tibia was significantly higher than others in control aged rat. Thus, recognizing the various histological reactions related to the time of epiphyseal closure is important for evaluating bone toxicity in aged rats.     

Pathological effects of Cryptostegia venusta toxicity in goats and rats

Here, we aimed to determine the toxicity of Cryptostegia venusta in goats and rats. We orally administered a single 60 g dose of shredded C. venusta leaves per kilogram of body weight to three goats. The animals were necropsied after death, and tissue sections were collected and routinely processed for histopathological analyses. Additionally, we separated 25 adult male Wistar rats (each weighing about 150 g) into five groups: an untreated control group and groups orally treated with 1, 3, 10, or 60 g/kg doses. Rats were sacrificed 72 h after administration of the C. venusta extract, and tissue sections collected for histopathological analyses. All goats presented signs of apathy, salivation, frequent urination, and eventually fatigue 4–6 h after receiving C. venusta. Two goats died 20 h after administration, and the third was sacrificed in extremis. The only histopathological finding observed in the goats was lung edema. No rats died during the experimental period or presented any clinical signs or macroscopic lesions. However, both goats and rats exhibited degeneration and multifocal necrosis of cardiac muscle fibers. From our results, we conclude that the C. venusta plant is capable of promoting cardiotoxicity.     

Effect of dietary alfalfa on zearalenone toxicity and metabolism in rats and swine

Experiments were conducted with rats and swine to determine the potential of dietary alfalfa as a treatment for zearalenone (Z) toxicosis. Ninety-six female weanling Wistar rats were fed a casein-based semipurified diet containing 0, 15 or 25% alfalfa and 0 or 250 micrograms Z/g feed. Exposure to Z for 14 d resulted in reduced growth, feed consumption and feed efficiency as well as kidney and liver enlargement and reduced activity of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD). Z had no effect on uterine weight. Including alfalfa in these diets reduced the inhibitory effects of Z on growth and feed consumption, minimized Z-induced liver enlargement and increased hepatic 3 alpha-HSD activity. Dietary alfalfa also reduced concentrations of residual Z and zearalenols (Zl) in liver. In a second experiment, 108 Yorkshire gilts weighing 8 to 11 kg were fed diets containing 0, 15 or 25% alfalfa and 0, 10, 20 or 40 micrograms Z/g feed for 4 wk. Z caused uterine enlargement when fed as low as 10 micrograms/g feed, although no effects were seen in growth rate, feed consumption or feed efficiency. Alfalfa decreased uterine enlargement (P less than .05), but caused a depression in feed efficiency (P less than .05). Hepatic 3 alpha-HSD activity was five times lower in swine than in rats, although activity still tended to decrease with Z and increase with alfalfa feeding. Residues of Z and Zl in pig liver indicated species differences in the metabolism of Z. These studies show that dietary alfalfa promotes Z metabolism in rats and that this feedstuff may also be useful for treating Z toxicosis in livestock.     

Curcumin mitigates fenthion-induced testicular toxicity in rats: histopathological and immunohistochemical study

Fenthion is a widely used organophosphorus pesticide in agriculture that induces different cytotoxic effects, including male reproductive toxicity. The present work aimed to study the ameliorative effects of curcumin, a potential therapeutic agent against several chronic diseases, on reproductive toxicity induced by the organophosphate insecticide fenthion. Forty adult male albino rats were divided into four groups. The control group received distilled water. The curcumin group was administered curcumin at a dose of 100 mg kg^?1 body weight. The fenthion group was administered fenthion at a dose of 0.001 mg kg^?1. The fenthion/curcumin group was administered fenthion and curcumin together at the same doses. After four weeks of daily oral administration, the animals were sacrificed and their testes were excised. Specimens were processed for histopatholological and immunohistochemical investigations. Light and electron microscopic analysis visualised dramatic degenerative changes in seminiferous tubules as indicated by atrophy, necrosis, vacuolation and decreased number of spermatogenic cells. Moreover, the fenthion group showed a significant reduction in the proliferating cell nuclear antigen (PCNA)-immunoreactivity. Decreased PCNA-immunoreactivity reflected the depletion in the proliferation rate of spermatogenic cells and suggesting arrested spermatogenesis. Curcumin administration to fenthion-treated rats revealed mild degenerative changes with partial improvement of active spermatogenesis. In conclusion, these data may confirm the cytoprotective potency of curcumin against fenthion-induced cyto-toxicity.     

Subchronic toxicity of gamma-Falisan-Universal dry dressing agent to rats

Doses of 50 mg/kg, 100 mg/kg, and 400 mg/kg of Gamma-Falisan-Universal dry dressing agent (active ingredients including 20 per cent of Lindan and 2.5 per cent of phenyl-mercury acetate) were administered in agar suspension by stomach intubation to rats over 13 weeks, with five applications weekly. The following changes were produced: retardation in body weight, lymphopenia and leucopenia, rise of segment-nuclear neutrophils in peripheral blood, decrease of haematocrit and haemoglobin, as well as rise in activities of leucine aminopeptidase and serum glutamate oxalo-acetate transaminase. The males proved to be more sensitive in the context of their haematological parameters, while the females displayed higher sensitivity in terms of clinico-chemical values. Absolute weight increases were recorded from kidneys and liver of both males and females and from the adrenal gland of females, while weight loss was recorded from the pituitary gland of males. Changes of the same kind were expressed even more strongly, in the context of relative weights of organs. Histopathological changes were recorded from liver, kidneys, and adrenal gland of either sex, and they were histometrically confirmed. Retardation in body weight, rise in activity of leucine aminopeptidase, and weight changes of various organs were significant up to first dosage group. Analogous findings were obtained with regard to microscopic changes in kidneys. Hence, no-effect levels did not occur at all throughout the experiment.     

A 13-week subchronic toxicity study of 2-(l-menthoxy)ethanol in F344 rats

2-(l-Menthoxy)ethanol has been frequently employed as a flavoring agent; however, data regarding 2-(l-menthoxy)ethanol toxicity remain limited. We performed a 13-week subchronic toxicity study of 2-(l-menthoxy)ethanol in male and female F344 rats, with doses of 0, 15, 60, or 250 mg/kg body weight (BW)/day orally administered by gavage using corn oil as the vehicle. No significant toxicological changes in general condition, body weight, or food intake were observed in any groups. The hematological assessment showed decreased hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin and increased platelet count in the male 250 mg/kg group. Serum biochemistry revealed elevated total cholesterol in the 250 mg/kg group of male and female rats, reduced triglyceride in the female 250 mg/kg group, and increased total protein in the male 250 mg/kg group, indicating effects on lipid metabolism and protein synthesis. For organ weights, absolute and relative weights of the liver and adrenal glands were increased in the 250 mg/kg group of both sexes and the male 250 mg/kg group, respectively. Histopathological analysis showed chronic nephropathy in the male 15 mg/kg or higher groups, with increased absolute and relative kidney weights, as well as elevated serum creatinine, in the male 60 and 250 mg/kg groups. However, eosinophilic granules containing α_2u-globulin were identified in proximal tubules, suggesting α_2u-globulin nephropathy specific to male rats and without toxicological significance. These results indicated that the no-observed-adverse-effect level of 2-(l-menthoxy)ethanol was 60 mg/kg BW/day for both sexes.     

Histopathologic and electron microscopic studies on the acute toxicity of ochratoxin A in rats

Ochratoxin A was given by gavage to male rats. Moribund and dead animals were necropsied, and the surviving rats, including the controls, were killed 48 hours after dosing. Many of the principal rats were moribund, or began dying, within 12 to 24 hours after dosing. Lesions suggestive of disseminated intravascular coagulation were seen by light microscopy as early as 12 hours after dosing; fibrin deposits were in the spleen, brain choroid plexus, glomerular capillaries, liver, and heart. Renal tubular nephrosis, hepatic and lymphoid necrosis, and necrotic enteritis with villous atrophy were also seen. Electron microscopy demonstrated fibrin strands mixed with degranulated platelets, necrotic leukocytes, and swollen endothelial cells in glomerular capillaries. Myocardial changes included focal supercontracted sarcomeres adjacent to intercalated disks. Swollen sarcolemma, lysed myofibrils and fragmented Z-bands with interstitial edema, vascular thrombosis, and endothelial damage were also seen. The acute pathologic changes induced by ochratoxin A in the intestine, liver, and lymphoid tissues were more obvious than the tubular nephrosis, and the development of a disseminated intravascular coagulation-like syndrome with myocardial changes was a complicating factor.