Developmental toxicity of orally administered 2',3'-dideoxycytidine in mice

2',3'-Dideoxycytidine (DDC), a potent inhibitor of human immunodeficiency virus (HIV), is presently undergoing clinical trials as a promising anti-AIDS drug. Since there are very limited published animal toxicity data available, and nucleoside analogues are being considered for treatment of HIV-infected pregnant women, a study was conducted in mice to investigate the potential adverse developmental effects of this drug. DDC, suspended in 0.5% methyl cellulose, was administered via gavage twice per day during gestation days (gd) 6 through 15 to C57Bl/6N mice in a total dose of 0, 200, 400, 1,000, or 2,000 mg/kg/day. Maternal weight gain during the gestation and treatment period, as well as gravid uterine weight, decreased significantly in the 2,000 mg group, but weight gain, corrected for gravid uterine weight, was not affected by DDC. The percent resorptions per litter increased significantly in the highest dose group, and there were fewer live litters because of complete litter resorption in six dams. Among litters with live fetuses, the mean litter size was significantly reduced in the 2,000 mg group. Average fetal body weight per litter decreased significantly in the 1,000 and 2,000 mg groups. The number of fetuses with any malformation, the number of litters with one or more malformed fetuses and the percent of malformed fetuses per litter increased significantly in the 1,000 and 2,000 mg groups. There was an increase in malformations at 400 mg/kg/day; however, it was not statistically significant. In conclusion, DDC produced developmental toxicity (malformations, reduced fetal body weight, and resorptions) in the absence of overt maternal toxicity except for body weight changes due to resorptions and reduced fetal weights.     

Licorice extract does not impair the male reproductive function of rats.

The effect of water extract of licorice (Glycyrrhiza uralensis), one of the most widely used medicinal plants in Oriental nations and in Europe, on male reproductive function was investigated in rats. Licorice extract was prepared as in Oriental clinics and orally administered at doses of 500, 1,000 or 2,000 mg/kg, the upper-limit dose (2,000 mg/kg) recommended in the Toxicity Test guideline of the Korea Food and Drug Administration, to 6-week-old male rats for 9 weeks. Licorice extract neither induced clinical signs, nor affected the daily feed consumption and body weight gain. There were no significant changes in testicular weights, gross and microscopic findings, and daily sperm production between vehicle- and licorice-treated animals, in spite of slight decreases in prostate weight and daily sperm production at the high dose (2,000 mg/kg). In addition, licorice did not affect the motility and morphology of sperm, although the serum testosterone level tended to decrease without significant difference, showing a 28.6% reduction in the high-dose (2,000 mg/kg) group. The results suggest that the no observed adverse-effect level of licorice extract is higher than 2,000 mg/kg, the upper-limit dose, and that long-term exposure to licorice might not cause profound adverse effects.     

Cytoprotective and anti-diabetic effects of Derris reticulata aqueous extract

The current study was aimed to investigate pancreatic protective and anti-diabetic activities of the aqueous extract of Derris reticulata stem. First, we evaluated a cytoprotective potential of D. reticulata extract on alloxan-induced damage in vitro. Treatment with D. reticulata extract at the doses of 250 and 500 μg/ml significantly increased cell viability of the pancreatic β-cell line RINm5F after exposure of alloxan. The anti-hyperglycemic activity of D. reticulata extract was further studied in alloxan-induced diabetic rats. A significant reduction in blood glucose level along with an increase in body weight was observed in diabetic rats treated with D. reticulata extract at 250 mg/kg body weight for 15 days. Serum aspartate transaminase and alanine transaminase levels were also significantly decreased compared to diabetic control rats. In accordance with in vitro cytoprotective effect, histopathological examination revealed that pancreatic islet cells of the extract-treated diabetic rat were less damage than those of the untreated diabetic group. In order to find another possible mechanism of action underling hypoglycemic activity, the effect on glucose absorption was examined using everted sac jejunum. The results showed that D. reticulata extract suppressed glucose absorption from small intestine. To corroborate safety use of D. reticulata extract, acute oral toxicity was also conducted in rats. Our results showed that none of the tested doses (250, 500, 1,000, and 2,000 mg/kg) induced signs of toxicity or mortality after administration of the extract. The results suggested that D. reticulata extract possess anti-diabetic activity, which resulting from its pancreatic cytoprotective effect and inhibition of intestinal glucose absorption.     

Safety and toxicological evaluation of Rhizopora mucronata (a mangrove from Vellar estuary,India): assessment of mutagenicity,genotoxicity and in vivo acute toxicity

The present was carried out to evaluate the toxicity of methanolic leaf extract of Rhizophora mucronata (MERM) under in vivo and in vitro conditions. Mutagenicity of MERM (up to 4,000 μg/plate) evaluated by Salmonella/microsome assay (TA98, TA100, TA1535 and TA1538 strains), with or without metabolic activation showed no mutagenic effect in any of the tester strain. Evaluation of genotoxicity (comet assay) and cytotoxicity in PBMC revealed that MERM showed no significant difference in comet tail moment (TM) and tail scores and cytotoxicity up to 24 h respectively. In acute toxicity studies, oral administration of single doses of MERM (250–2,000 mg/kg) in Wistar rats produced neither mortality nor any noticeable changes in behavior. Hematological and biochemical parameters showed no difference, except for a significant increase in ALT and AST at the highest dose. Histopathological findings revealed hepatotoxicity and neurotoxicity at highest dose of extract. In subacute toxicity studies administration of MERM (1,000 mg/kg) for 28 consecutive days neither altered the body weight gain nor behavioral parameters. No significant change was observed in the hematological and biochemical parameters analyzed. Histopathological examination showed normal architecture suggesting no morphological disturbances. Collectively, these data demonstrate that consumption of MERM for various medicinal purpose is safe.     

Developmental toxicity evaluation of berberine in rats and mice

BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health-related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice. METHODS: Berberine chloride dihydrate was administered in the feed to timed-mated Sprague-Dawley (CD) rats (0, 3,625, 7,250, or 14,500 ppm; on gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3,500, 5,250, or 7,000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1,313 mg/kg/day (rats) and 0, 569, 841, and 1,155 mg/kg/day (mice). RESULTS: There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7,250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5,250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1,000 mg/kg/day was conducted in both species. CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7,250 ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL was raised to 1,000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5-6% with no change in live litter size. The maternal toxicity LOAEL remained at 5,250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1,000 mg/kg/day BCD based on decreased fetal body weight.     

Acute and subacute toxicity of 10B-paraboronophenylalanine

The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.     

Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex

Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.     

Evaluation of Bacillus subtilis SPB1 Lipopeptide Biosurfactant Toxicity Towards Mice

The in vivo potential toxicity of SPB1 lipopeptide biosurfactant towards male mice was evaluated. An LD50 value (defined as the dose required to kill half the members of a tested population) was determined to be about 475 mg/kg. Results show that daily administration of SPB1 biosurfactant did not show any death cases at any dose. Also, no unusual changes in behavior and no intoxication were observed during the 28 days period of treatment. Analysis proved that there were no significant differences in the serum glucose concentration levels, plasma total cholesterol, aspartate aminotransferase activity and bilirubin concentration among the control and experimental groups. In contrast, a little enhancement of alanine aminotransferase activities was observed for mice treated by the highest dose of the biosurfactant corresponding to 47.5 mg/kg of body weight which indicated the necrosis of hepatocyte. A daily intake of doses lower than 47.5 mg/kg of body weight had no significant adverse effect on hematological parameters and serum biochemical data. These results proved that SPB1 biosurfactant could be of a great interest as an additive in food, cosmetic and pharmaceuticals fields.     

Toxicity profiling of the ethanolic extract of Citrullus lanatus seed in rats: behavioral,biochemical and histopathological aspects

Citrullus lanatus (Cucurbitaceae) is conventionally used for the treatment of urinary tract infection, renal stones, hypertension, diabetes and diarrhoea. Current study evaluates acute and 28 days repeated toxicity ethanolic extract of C. lanatus seed (EECLS) in Wistar rats to measure its safety profile. The single dose (2000 mg/kg BW) of EECLS was administered while in 28 days repeated study 250, 500 and 1000 mg/kg BW were administered orally in rats. Parameters such as biochemical, haematological and histopathological were analysed in subacute toxicity study. During study, no apparent sign of toxicity, behavioural changes and mortality were detected in acutely exposed animals. In 28 days repeated toxicity study, rats did not show significant changes in behaviour, gross pathology, body weight, biochemical and haematological parameters. Abridged serum glucose and cholesterol levels during the study designate their roles in treatment of hyperglycaemic and hyperlipidaemic conditions. No significant difference was observed in histopathology of liver and kidneys of treated rats. The current investigation demonstrated that EECLS is non-toxic below 1000 mg/kg BW and provides protection to some body organs. The data propose that LD₅₀ of EECLS was greater than 2000 mg/kg BW and the no observed adverse effect level (NOAEL) of EECLS was at the dose of 1000 mg/kg in rats. Taken together, our finding suggests that, EECLS is safe and provides some protection to body organs; also, its extract can be used for further preclinical and clinical evaluation for its therapeutic activity.     

Embryotoxicity studies of norfloxacin in cynomolgus monkeys: I. Teratology studies and norfloxacin plasma concentration in pregnant and nonpregnant monkeys

Norfloxacin, a new orally active antibiotic, was investigated in cynomolgus monkeys for potential developmental toxicity. Fifty-seven monkeys were administered a control vehicle or norfloxacin by nasogastric gavage during the major period of organogenesis on gestational days (GD) 21 through 50 at doses of 0, 50, 100, 150, or 200/300 mg/kg/day. There was no evidence of teratogenicity at any dose level. Maternotoxicity and a significant increase in embryolethality occurred following doses of 200/300 mg/kg/day. The maternotoxicity was not expected based on range-finding studies in nonpregnant female monkeys, which showed no signs of toxicity in doses up to 500 mg/kg/day. Additional studies were conducted to determine if norfloxacin caused similar toxicity later in gestation. Forty-six pregnant monkeys were dosed with a control vehicle or 200 mg/kg/day norfloxacin for one of three 10-day periods on GD 36-45, 71-80, or 111-120. There were no maternotoxic, embryotoxic, or fetotoxic effects observed. Plasma concentrations of norfloxacin in five cynomolgus monkeys following 50 and 200 mg/kg oral doses were not dose-proportionate. However, at a given dose, administered in cross-over fashion, plasma concentrations of norfloxacin were higher in nonpregnant females (approximately 20-40%) than during pregnancy when the same subject was compared. At the no-observed-effect dose for maternal and embryotoxicity (50 mg/kg), peak plasma concentrations of norfloxacin in pregnant cynomolgus monkeys are approximately threefold higher than those observed in human volunteers receiving norfloxacin at the maximum recommended therapeutic dose of 400 mg (5.7 mg/kg based on 70 kg body weight) twice per day.     

Developmental toxic effects of antifungal flusilazole administered by gavage to mice

BACKGROUND: The developmental toxicity of flusilazole was studied in CD-1 mice after oral administration. METHODS: Pregnant mice were given flusilazole at doses of 0 (corn oil), 10, 20, and 40 mg/kg/day, by gavage, on gestational days (GD) 6-15. RESULTS: Maternal toxicity, as evidenced by reduction in body weight gain and signs of toxicity, was observed at the middle- and high-dose groups. No significant incidence of resorptions or death was observed in any of dose groups. There was a pronounced reduction in fetal weight, which was significantly lower than control from 20 and 40 mg/kg/day. There was no significant increase in the incidence of fetuses with external or visceral malformations in any of dose groups, but there was a significant increase in the incidence of skeletal malformations was observed at 20 and 40 mg/kg/day. CONCLUSIONS: The results of this study reported marked maternal toxicity, growth retardation, and skeletal abnormalities in the mid- and high-dose groups. It seems likely that marked maternal toxicity contributed to the observed alterations in fetal growth retardation and skeletal development. The no-observed-effect level in the present study for maternal and developmental toxicity was 10 mg/kg/day.     

Combined embryotoxic action of toluene, a widely used industrial chemical, and acetylsalicylic acid (aspirin)

CFY rats were exposed to inhalation of fresh air at days 10-13 of gestation; at day 12 the dams were given 0, 125, 250, 500, or 1,000 mg/kg acetylsalicylic acid (ASA) by gavage. During the same period of gestation (days 10-13) further groups of rats were exposed to toluene at 1,000, 2,000, and 3,600 mg/m3 atmospheric concentration and were given 250 mg/kg ASA by gavage; two subgroups of animals treated with 250 mg/kg ASA in combination with 3,600 mg/m3 toluene inhalation were given 0, 2.5, or 5 gm/kg glycine 2 hours before the ASA dose. At day 21 the animals were killed and examined for teratogenic effects and histological changes. After 48 hours toluene exposure other groups of rats were treated with ASA or with ASA plus glycine (administered 2 hours earlier) on day 20 of gestation. These animals were killed 2 hours later and the salicylic acid concentration in maternal and embryonic plasma and in amniotic fluid was measured by gas chromatography. With the rising ASA doses both maternal toxicity (increased mortality, decreased food consumption, and weight gain) and embryonic toxicity (postimplantation loss, increased incidence of weight-retarded fetuses, increased minor anomalies and malformations, decreased average weight of fetuses) increased. Toluene was found to potentiate the toxic effect of ASA and to increase both maternal and embryonic toxicity. The type of ASA-induced minor anomalies and malformations was also found to be altered under the effect of toluene pretreatment. By raising the toluene concentration the salicylic acid level in the maternal and embryonic plasma and in the amniotic fluid was increased above the expected concentration. The mechanism of the potentiating interaction should be looked for in the depletion of the glycine pool by toluene (and its metabolites) and in the resultant increase of salicylic acid level. Increasing ASA embryotoxicity caused by toluene can be warded off by glycine administration.     

Maternal and developmental toxicity of low doses of cytosine arabinoside in mice

1-beta-D-Arabinofuranosylcytosine (Ara-C), an effective drug for the treatment of leukemia and breast cancer, was evaluated for developmental toxicity in pregnant Swiss mice. Ara-C was administered by intraperitoneal injection on gestational days 6-15 at doses of 0, 0.5, 2, and 8 mg/kg/day. Maternal observations included clinical signs, body weight change, food consumption, and gross evaluation of organs and uterine contents at necropsy (day 18). Live fetuses were examined for external, visceral, and skeletal alterations. Maternal toxicity was observed at 2 and 8 mg/kg/day, as evidenced by a significant decrease in body weight gain and food consumption during the treatment period. Significantly increased early and late resorptions and reduced number of live fetuses per liter as well as decreased fetal body weight were observed at 8 mg/kg/day. At 2 mg/kg/day, the incidence of cleft palate, renoureteral agenesis or hypoplasia, and poly- or oligodactyly was significantly increased, whereas fetal weight was reduced at 0.5 mg/kg/day. Thus, the developmental no-observed-adverse-effect-level (NOAEL) of Ara-C in the pregnant mouse is lower than 0.5 mg/kg/day, while the NOAEL for maternal toxicity is 0.5 mg/kg/day. We believe that exposure to this agent ought to be avoided during organogenesis.     

Alternative treatment for Anacanthorus penilabiatus (Monogenea: Dactylogyridae) infection in cultivated pacu,Piaractus mesopotamicus (Osteichthyes: Characidae) in Brazil and its haematological effects

The present work, studied the effect of 0, 1,000, 1,500 and 2,000 mg of garlic powder/kg dry ration for Piaractus mesopotamicus (Osteichthyes: Characidae), weighting 73.6 +/- 39.4 g and measuring 15.0 +/- 2.7 cm, fed for a period of 15, 30 and 45 days. Fifteen days after treatment with 1,000 and 2,000 mg of garlic/kg dry ration, significant reduction of Anacanthorus penilabiatus (Monogenea: Dactylogyridae) in the gills was related. Nevertheless, the addition of garlic to the ration caused significant increase in the erythrocyte number and in the thrombocyte percentage in the circulating blood. However, a decrease in the lymphocyte percentage was also observed. After 45 days, fish fed with garlic showed significant increase in the erythrocyte number, leucocyte, haemoglobin rate, hematocrit and thrombocyte.     

Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

Background

With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans.

Methods

In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment.

Results

Death of mice in the highest dose (1387 mg/kg) group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC) count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW) coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice.

Conclusions

Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.     

Acute toxicity of combinations of sodium dichromate, sodium arsenate and copper sulphate in the rat

1. The intraperitoneal treatment of adult male Wistar rats with various combinations of low doses of sodium dichromate (5 mg/kg), sodium arsenate (25 mg/kg) and copper sulphate (5.9 mg/kg) tended to counteract the inherent acute toxicity of each compound. 2. The co-administration of low doses of one or more of the test compounds with a high dose of sodium dichromate (35 mg/kg), sodium arsenate (90 mg/kg) or copper sulphate (23.5 mg/kg) resulted in a significant increase in acute toxicity in comparison with that produced by the administration of high doses of dichromate, arsenate or Cu2+ alone.     

Effect of aqueous fruit extract of xylopia aethiopica on intestinal fluid and glucose transfer in rats

Intestinal fluid and glucose absorption was studied in jejunal and ileal segments in Xylopia aethiopica fed rats using inverted sac technique. Thirty male Wistar rats were assigned into three groups of 10 rats each; control, 100mg/kg and 200mg/kg Xylopia aethiopica treated groups. The control group received normal rat chow and water while the low dose and high dose groups received oral administration of Xylopia aethiopica extract at doses of 100mg/kg and 200mg/kg body weight respectively in addition to daily rat chow and water intake for 28 days. The results showed significant reduction and increase in fluid transfer in the jejunum and ileum respectively compared with control. 100mg/kg increased gut fluid uptake in the ileum while 200mg/kg treatment reduced uptake in jejunum compared with control. Both doses had significantly increased jejunal and ileal glucose transfer. Gut glucose uptake was increased in jejunum and ileum of Xylopia aethiopica treated groups. Both doses increased the crypt depth but significantly decreased the villus height in the ileum. In conclusion, increased ileal gut fluid uptake may be beneficial in diarrheal state while an enhanced glucose uptake implies that glucose substrate may be made available to cells for synthesize of ATP for cellular activities. Keywords: Xylopia aethiopica, Glucose, Absorption, Jejunum, Ileum, Rat.     

Developmental toxicity evaluation of orthovanadate in the mouse

Sodium orthovanadate in deionized water was administered once daily by gavage on gestational days 6-15 to mice at doses of 0, 7.5, 15, 30, and 60 mg/kg. Dams were killed on day 18 of pregnancy, and fetuses were examined for external, visceral, and skeletal defects. Maternal toxicity was observed at the highest doses of sodium orthovanadate, as evidenced by a significant number of deaths (60 and 30 mg/kg/d) and reduced weight gain and food consumption (30 and 15 mg/kg/d). Embryolethality and teratogenicity were not observed at maternally toxic doses and below, but fetal toxicity was evidenced by a significant delay in the ossification process of some skeletal districts at 30 mg/kg/d. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 7.5 mg/kg/d, and 15 mg/kg/d represented a NOAEL for developmental toxicity in mice under the conditions of this study.     

Assessment of toxicological effects of mancozeb in male rats after chronic exposure

Mancozeb, an ethylenebisdithiocarbamate fungicide was administered orally to male rats at doses 0, 500, 1000 and 1500 mg/kg/day for 90, 180 and 360 days produced dose dependent signs of poisoning, loss in body weight gain and mortality. However the signs of toxicity and mortality were more pronounced initially at 0-90 days as compared to 90-360 days of treatment period. A significant increase in the relative weight of liver and slight decrease in the kidney weight were observed in animals exposed to mancozeb (1000 and 1500 mg/kg/day) for 180 and 360 days associated with pathomorphological changes in liver, brain and kidney. Mancozeb has produced significant enzymatic changes in the activities of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) throughout the period of study in a dose dependent manner. The alterations in the activity of enzymes associated with pathomorphological changes suggest that the chronic exposure of mancozeb produced significant toxicological effects in rats.     

Effects of Se-enriched polysaccharides produced by Enterobacter cloacae Z0206 on alloxan-induced diabetic mice

In this study, the water-soluble selenium-enriched exopolysaccharides (Se-ECZ-EPS) were isolated from submerged culture broth of Enterobacter cloacae Z0206 through fermentation, ethanol precipitation and deproteinization. The protective effects of Se-ECZ-EPS on alloxan-induced diabetic mice were investigated. Diabetes was induced in ICR (Institute of Cancer Research) mice by administration of single doses of alloxan intraperitoneally (190 mg/kg body weight). Se-ECZ-EPS at a dose of 200 mg/kg body weight were administered per os (p.o.) as single dose per day to diabetes-induced mice for a period of 42 days. The decrease in body weight, serum insulin level, and the increase in blood glucose level, glycosylated serum protein (GSP), total cholesterol (TC) and triglycerides (TG) in liver were observed in diabetic mice. On the other hand, oral administration of Se-ECZ-EPS resulted in a significant reduction in fasting blood glucose levels, GSP, TC and TG contents in liver coupled with improvement of body weight and serum insulin level in comparison with diabetic control group. These results suggest that Se-ECZ-EPS possess significant protective and anti-diabetic effects in alloxan-induced diabetic mice.