This study was undertaken to determine the bioavailability of isoflavones in weanling Sprague-Dawley rats by providing diets containing different levels of soy isoflavones for 6 weeks: 0.025% (low isoflavone intake; LI), 0.125% (medium isoflavone intake; MI), and 0.25% (high isoflavone intake; HI). The subsequent fecal and urinary excretion of daidzein and genistein was then measured. As the levels of dietary isoflavones increased, the amount of food intakes significantly decreased, and weight gain was slower in female rats. In male rats, there was no significant difference in weight gains related to dietary intakes. Urinary excretion of daidzein and genistein was significantly higher in the MI and HI groups in both male and female rats than the control and LI groups. The recovery % of daidzein and genistein in the urine was significantly lower in the MI and HI groups. Fecal daidzein increased as dietary isoflavone intakes increased in female rats; however, in male rats the increase was significant only in the HI group. The recovery % of daidzein and genistein in the feces of female rats was not significantly different among the four groups. When dietary isoflavones were increased from 0.025% to 0.25%, the amounts of daidzein and genistein excreted in the urine and feces increased; however, the low recovery rate of both daidzein and genistein in the urine implies an increased bioavailability of isoflavones. We also observed sex-related differences in the urinary and fecal recovery of isoflavone intakes.
The effect of KTC-1, a new semisynthetic rifamycin antituberculous drug, on general toxicity, reproductive capability and fetal development was investigated in Sprague-Dawley rats. Male rats were administered KTC-1 with mashed feed from 63 days before mating to the end of mating period, and female rats were given from 14 days before mating to day 7 of gestation at dose levels of 0, 375, 750, and 1,500 ppm. The females were sacrificed on day 21 of gestation for examination of their fetuses. At 1,500 ppm, a reduction in body weight gain and testis atrophy were observed in male rats. Histological examination revealed testicular atrophy, absence or decrease of germinal cells, and vacuolization of Sertoli cells in testis. A reduction in body weight gain, a decrease in food consumption were found in female rats. In addition, decreases in the number of corpora lutea, iraplantations, and the litter size of live fetuses were seen. Mating, fertility, and pregnancy performances were also affected. There were no external abnormalities observed by examination of fetuses. At 750 ppm, a reduction in the body weight gain of male and female rats and decreases in the number of implantations and litter size were found. At 375 ppm, no treatment-related effects were observed. The results suggest that the no-effect dose levels (NOELs) of KTC-1 are 375 ppm for males and females on general toxicity, 750 ppm for males and females on reproductive capability, and 375 ppm for fetuses on embryonic development.
The purpose of this study is to investigate the pharmacokinetics and tissue distribution of recombinant bovine somatotropin (rBST) after subcutaneous adminstration of $^{125}I-rBST$ in male and female rats. A solid state conjugation (Iodo-bead$^{(R)}$) method was confirmed useful for producing $^{125}I-rBST$ because the administration of the conjugated form enabled enough to determine time- concentration relationships of rBST in rats. Subcuatenous administrations showed sex differences that female ($t_{1/2,kc}$, 2.87 h) revealed rapid elimination as compared to male ($t_{1/2,ke}$, 4.81 h), with the absorption ($t_{1/2,ka}$ in male being 0.3 h and that in female 0.75 h) in the reverse order. For subcutaneous administration of rBST in male rats, the liver was the highest in amount, followed by kidney, testes, muscle, and stomach, at the slaughtering tame of 1, 6, 12 and 24 h. But the testes was the highest at the 48 h slaughtered animals, followed by liver, kidney, stomach, and muscle. In slaughtered females at 1, 6, and 12 h after the administration of rBST, the liver was the highest, followed by ovary, kidney, small intestine, and stomach. At 24 and 48 h slaughtered female rats, the ovary was the highest, the liver the second, and the kidney the third.
Asiabanha, Majid;Asadikaram, Gholamreza;Rahnema, Amir;Mahmoodi, Mehdi;Hasanshahi, Gholamhosein;Hashemi, Mohammad;Khaksari, Mohammad
The Korean Journal of Physiology and Pharmacology
/
v.15
no.6
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pp.327-332
/
2011
It has been shown that some opium derivatives promote cell death via apoptosis. This study was designed to examine the influence of opium addiction on brain and liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium-addicted, diabetic and diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL and DNA fragmentation assays. Results of this study showed that apoptosis in opium-addicted and diabetic opium-addicted brain and liver cells were significantly higher than the both normal and diabetic rats. In addition, we found that apoptosis in brain cells of opium-addicted and diabetic opium-addicted male rats were significantly higher than opium-addicted and diabetic opium-addicted female, whereas apoptosis in liver cells of opium-addicted and diabetic opium-addicted female rats were significantly higher than opium-addicted and diabetic opium-addicted male. Overall, these results indicate that opium probably plays an important role in brain and liver cells apoptosis, therefore, leading neurotoxicity and hepatotoxicity. These findings also in away possibly means that male brain cells are more susceptible than female and interestingly liver of females are more sensitive than males in induction of apoptosis by opium.
Sexually mature male and female rats were orally intubated with the organophosphorus insecticide, Pestban at a daily dosage of 7.45 or 3.72 mg/kg bwt, equivalent to 1/20 and 1/40 $LD_{50}$, respectively. Male rats were exposed for 70 days, while the female rats were exposed for 14 days, premating, during mating and throughout the whole length of gestation and lactation periods till weaning. The results showed depressed acetylcholinesterase(AChE) activity in the brain of parents, fetuses and their placentae in a dose-dependent manner. The fertility was significantly reduced with increasing the dose in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre-and postimplantation losses were significantly increased. The incidence of resorptions was more pronounced in treated female compared to male group and was dose dependant. The behavioral responses as well as fetal survival and viability indices were altered in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group and occurred in a dose-related manner. The recorded morphological, visceral, and skeletal anomalies were significantly increased with increasing the dose in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to Pestban would cause adverse effects on fertility and reproduction.
This study was carried out to investigate the effect of selenium on the adriamycininduced renal lesions in male Sprague Dawley rats. A total of 60 Sprague-Dawley male rats were divided into 2 control groups(C1: saline, C2: selenium) and 2 treatment groups(T1: adriamycin, T2: adriamycin+selenium). The rats of the C1 and T1 groups were given normal saline(0.15ml/rat), the rats of the C2 and T2 groups were given sodium selenite(0.5mg/kg) intraperitoneally three days a week for 4 weeks. The treatment groups were dosed intraperitoneally with adriamycin(2mg/kg/day) five days at the second week. Animals were sacrificed at the 1st week, 2nd week and 3rd week after dosing with adriamycin. The morphologic abnormalities of the glomeruli and tubules in the kidney of male rats were examined histopathologically and electron microscopically.The results obtained were as follows : The mean body weight of adriamycin dosed group was significantly decreased as compared with that of control group at 4th week(p<0.05). In adriamycin and selenium dosed group, the mean body weight was decreased until the end of 2nd week but gradually increased from 3rd to 4th week. The histopathological findings of the renal corpuscle in adriamycin dosed group were parietal epithelial cell proliferation, vacuolization of glomerulus, and thickened basement membrane of the parietal epithelium. Proximal convoluted tubules were significantly dilated and the lumens were filled with renal cast. These lesions were generally not very significant in the rats given adriamycin and selenium. The electron microscopical findings of the renal glomerulus in the adriamycin dosed group were focal loss and fusion of the pedicels of the podocyte, and some vacuoles in the cytoplasm of the podocytes. There were numerous cytoplasmic vacuoles in the proximal and distal convoluted tubular cells. However, these ultrastructural changes were not significantly observed in the renal tubules of the rats of adriamycin and selenium dosed group. These results suggest that selenium may act as an inhibitor of the renal lesions induced by adriamycin in male rats.
Ethyl formate, a volatile solvent, has insecticidal and fungicidal properties and is suggested as a potential fumigant for stored crop and fruit. Its primary contact route is through the respiratory tract; however, reliable repeated toxicological studies focusing on the inhalation route have not been published to date. Therefore, the present study was conducted to investigate the safety of a 90-day repeated inhalation exposure in rats. Forty male and 40 female rats were exposed to ethyl formate vapor via inhalation at concentrations of 0, 66, 330, and 1,320 ppm for 6 hr/day, 5 days a week for 13 weeks. Clinical signs, body weights, food consumption, urinalysis, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathological findings were compared between the control and ethyl formate-exposed groups. Locomotor activity decreased during exposure and recovered afterward in male and female rats exposed to 1,320 ppm ethyl formate. Body weight and food consumption continuously decreased in both sexes exposed to 1,320 ppm ethyl formate from week 1 or 3 compared with the control values. The increases in adrenal weight and decreases in thymus weight were noted in both sexes exposed to ethyl formate at 1,320 ppm. Degeneration, squamous metaplasia of olfactory epithelium in the nasopharyngeal tissue, or both were noted in the male and female rats at 1,320 ppm and female rats at 330 ppm ethyl formate. Taken together, our results indicate that ethyl formate-induced changes were not observed in male and female rats at 330 and 66 ppm, respectively. This indicates that exposure to ethyl formate at concentrations below 66 ppm for 90 days is relatively safe in rats. This is the first report of a full-scale repeated inhalation toxicity assessment in rats and could contribute to controlling occupational environmental hazards related to ethyl formate.
Objectives: This toxicological study was performed to assess for potential toxicity and to determine the approximate lethal dose of SU-Eohyeol pharmacopuncture (SUEP) following a single intramuscular injection of SUEP into male and female Sprague-Dawley (SD) rats. Methods: The groups in our experiment consisted of an experimental group treated with SUEP at a dose of 1.0 mL/animal and a control group injected with a normal saline solution, and five male and female rats were placed in each group. Each animal was administered a single intramuscular injection. We monitored all rats for clinical signs and body weight changes for 14 days after administration. At the end of the observation period, the rats were euthanized and autopsied, and localized tolerance examinations were conducted at the site of administration of the test substance. Results: There were no deaths in either sex in the SUEP-treated group. There was no significant difference between the SUEP-treated group and the control group in the clinical signs and weight changes among the rats. In addition, no significant SUEP-related changes were observed on autopsy findings or local tolerance examinations at the injection site by histopathological examination. Conclusion: Our results suggest that the approximate lethal dose of a single intramuscular administration of SUEP in female and male rats under the conditions of this study is greater than 1.0 mL/animal. To determine the safety of the use of SUEP in Korean medical clinical practice, additional toxicity studies will be needed.
The object of this study was to evaluate the single oral dose toxicity of Low Molecular Weight Fucoidan (LMF) in male and female rats. LMF was administered to female and male SD rats as an oral dose of 2,000, 1,000 and 500 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation organ weight and histopathology of 14 principle organs were examined upon necropsy. As the results, no LMF treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2,000 mg/kg in both female and male rats except for some sporadic findings not LMF treatment related toxicological signs. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of LMF after single oral treatment in female and male rats were considered over 2,000 mg/kg - the limited dosages recommended by KFDA Guidelines [2005-60, 2005], respectively.
Journal of the Korean Society of Food Science and Nutrition
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v.12
no.3
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pp.273-283
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1983
In order to investigate the effect of the combined dietary animal and vegetable proteins on growing female and male rats and mice. 25 female and 25 male rats of 4 weeks old weighing approximately 43-65g and 47-60g, respectively, were subjected to feeding trials for 4 weeks and then subsequently to metabolic trials for 10 days. In case of mice, 25 female and 25 male mice of 4 weeks old weighing approximately 12-17g and 12-16g, respectively, were equally treated. The dietary energy level was set as 3600 kcal ME/kg, and protein and fat provided respectively 12 and 5% of the dietary energy. The rest 83% of the energy level was supplied with appropriate amounts of starch and glucose. The following results were obtained. The body weight gain of female and male rats were increased as the combined dietary animal protein level increased. Whereas that of male mice was the highest for the diet E(Ap 10+Vp 90). Food efficiencies both of female and male rats were improved as combined dietary of animal protein increased. Male rats were superior to that of female. In the mice, the food efficiency value of male mice was superior to that of female. And the values of the male showed the same fashion as that in the growth rate, although it was not for the female. Protein efficiencies, both of female and male rats, were improved as combined dietary of animal protein level increased. That of male mice was in accord with the body weight gain and food efficiencies. But that of female mice was not accordant. Nitrogen retention of the experimental diets in the same protein level was in proportion to nitrogen intake. That of male mice was improved as animal protein level increased, but, that of female mice was not. Body protein utilizability was found to be superior in mice to rats. Blood serum protein level was not found to be affected by the experimental diets in the same protein level. The best combination ratio of animal and vegetable protein seems to be variable depending on the sex and species of animals, and the best diets for female and male rats and female and male mice were found to be experimental diet A(Ap 10+Vp 90) or diet B(Ap 75+Vp 25), diet C(Ap 50+Vp 50), and diet E(Ap 10+Vp 90), respectively. From the above-mentioned results that there was no difference in growth rate of body weight gain from the weanling period to puberty, and that the protein requirements of rats and mice were different from each other.
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