Physiological effects of lactulose and inulin in the caecum of rats

A model experiment was performed on rats to evaluate the effect of partial or total substitution of saccharose (S) and cellulose (C) by preparations of lactulose and inulin on the development and metabolism of the caecum. In the experimental diets given to rats for 4 weeks, the examined preparations were administered either with an equivalent amount of cellulose (each at 4% of the diet) or as sole source of dietary fibre at 8% of the diet. Compared to the saccharose group cellulose had no effect, and low doses of lactulose and inulin in the diet increased to a medium extent the weight of the caecum wall and caecal digesta. The addition of lactulose and inulin at 8% increased significantly the content of caecal digesta (4.62 and 4.11?g/100g BW, respectively) and the weight of the caecal wall (1.10 and 0.86?g/100g BW, respectively), compared to the groups with saccharose and cellulose (0.73, 0.90 and 0.24, 0.28?g/100g BW, respectively). Cellulose and cellulose partially-substituted with lactulose and inulin caused an increase in the dry matter content of caecal digesta (26.5–27.5%), compared to other groups (21.8–22.8%). The administration of lactulose and inulin preparations was accompanied by a significant drop in pH (5.47–5.81), compared to the groups with cellulose or saccharose (6.83–6.91), and a decrease in the ammonia concentration in the caecal digesta, compared to the cellulose control (0.27–0.40 and 0.62?mg/g, respectively). The group with 8% lactulose was characterized by the highest activities of microbiological α- and β-galactosidase and β-glucosidase in the caecal digesta. Cellulose and both preparations significantly decreased the activity of β-glucuronidase, compared to the saccharose group (0.39–0.89 and 1.52?U/g, respectively). The highest concentration of VFA in the caecal digesta was observed in the saccharose group (89.2?μmol/g), and the lowest concentration in the group where cellulose was totally substituted by lactulose and inulin (55.1 and 57.5?μmol/g, respectively). The total production of VFA in the caecum was fourfold higher with 8 % lactulose and inulin (254.7 and 236.4?μmol/100g BW, respectively) than in both controls groups (65.1 and 67.8?μmol/100g BW, respectively). The high dose of inulin and lactulose increased the share of propionic acid in the VFA profile (C₂:C₃:C₄) compared to both control groups. When 4% inulin was added to the diet a significant increase of butyrate concentration in the caecum was observed.     

Physiological effects of lactulose and inulin in the caecum of rats

A model experiment was performed on rats to evaluate the effect of partial or total substitution of saccharose (S) and cellulose (C) by preparations of lactulose and inulin on the development and metabolism of the caecum. In the experimental diets given to rats for 4 weeks, the examined preparations were administered either with an equivalent amount of cellulose (each at 4% of the diet) or as sole source of dietary fibre at 8% of the diet. Compared to the saccharose group cellulose had no effect, and low doses of lactulose and inulin in the diet increased to a medium extent the weight of the caecum wall and caecal digesta. The addition of lactulose and inulin at 8% increased significantly the content of caecal digesta (4.62 and 4.11 g/100g BW, respectively) and the weight of the caecal wall (1.10 and 0.86 g/100g BW, respectively), compared to the groups with saccharose and cellulose (0.73, 0.90 and 0.24, 0.28 g/100g BW, respectively). Cellulose and cellulose partially-substituted with lactulose and inulin caused an increase in the dry matter content of caecal digesta (26.5-27.5%), compared to other groups (21.8-22.8%). The administration of lactulose and inulin preparations was accompanied by a significant drop in pH (5.47-5.81), compared to the groups with cellulose or saccharose (6.83-6.91), and a decrease in the ammonia concentration in the caecal digesta, compared to the cellulose control (0.27-0.40 and 0.62 mg/g, respectively). The group with 8% lactulose was characterized by the highest activities of microbiological alpha- and beta-galactosidase and beta-glucosidase in the caecal digesta. Cellulose and both preparations significantly decreased the activity of beta-glucuronidase, compared to the saccharose group (0.39-0.89 and 1.52 U/g, respectively). The highest concentration of VFA in the caecal digesta was observed in the saccharose group (89.2 micromol/g), and the lowest concentration in the group where cellulose was totally substituted by lactulose and inulin (55.1 and 57.5 micromol/g, respectively). The total production of VFA in the caecum was fourfold higher with 8 % lactulose and inulin (254.7 and 236.4 micromol/100g BW, respectively) than in both controls groups (65.1 and 67.8 micromol/100g BW, respectively). The high dose of inulin and lactulose increased the share of propionic acid in the VFA profile (C2:C3:C4) compared to both control groups. When 4% inulin was added to the diet a significant increase of butyrate concentration in the caecum was observed.     

Gonadal toxicity of short term chronic endosulfan exposure to male rats

Endosulfan was studied for its effect on rat testicular toxicity in relation to the enzymes of androgen biosynthesis, viz. 3 beta-hydroxysteroid dehydrogenase (EC 1.1.1.145, 3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (EC 1.1.1.64, 17 beta-HSD); cytosolic conjugation enzyme, glutathione-S-transferase (EC 2.5.1.18); and testicular as well as serum testosterone levels at the dose levels of 2.5, 5.0, 7.5 and 10 mg/kg body weight fed orally for 7 and 15 days. Organ and body weights of the treated animals did not change significantly, however, the testicular protein contents were found to be increased appreciably after 7 days treatments. The activity profile of cytosolic conjugation enzyme showed much remained low during 7 days treatment, however, the two steroidogenic enzymes showed much individual variations in response to endosulfan treatments. An overall varied response with respect to testosterone biosynthesis and its secretion to serum was observed suggesting nevertheless, a profound hormonal imbalance caused by this insecticide to male gonads on short term chronic exposures.     

Analysis of historical control litter parameters of reproduction toxicity studies in Sprague-Dawley derived rats

Control litter data from reproduction toxicity studies in SD derived rats bred in our closed colony were investigated for historical changes, differences due to study design or generations, seasonal variations and effects of vehicle-treatment. The litter size did not change visibly during the entire 16-year period, but the number of live fetuses differed significantly between study designs or generations. The fetal weight gradually increased during these years. The malformation rate decreased, while the rate of 14 th ribs remained stable. There were no seasonal variations and no effects of vehicle-treatment.     

Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats

BACKGROUNDS: Recently, potential liver toxicity was discussed with the intake of kava extract preparations (Piper methysticum) as anxiolytic drugs. The aim of this study was to test chronic toxicity in rats by oral application of an ethanolic kava full extract. METHODS: Wistar rats of both sexes were fed 7.3 or 73 mg/kg body weight of ethanolic kava extract for 3 and 6 months. The animals were examined for changes in body weight, hematological and liver parameters, and macroscopical and microscopical histological changes in the major organs. RESULTS: No signs of toxicity could be found. CONCLUSIONS: The results are in accordance with the medical experience regarding the use of kava preparations and the long tradition of kava drinking in the South Pacific island states. Specifically, the results do not back the suspicion of potential liver toxicity.     

Intestinal permeability to lactulose and mannitol in growing rats with iron-deficiency anemia

Iron deficiency can have nonhematological manifestations, some of which may affect the gastrointestinal tract. The aim of this study was to determine if iron-deficiency anemia in growing rats affected small-bowel permeability as assessed by the urinary ratio of lactulose and mannitol. Thirty-seven male Harlan Sprague-Dawley rats (21 d of age) were randomly divided into two groups and fed either an iron-deficient (n=19) or an iron-sufficient diet (n=18) that contained either 13.5 or 43.8 mg of iron/kg diet, respectively. Animals were evaluated between 25 and 38 d of dietary treatment. Intestinal permeability was assessed by measuring the lactulose/mannitol urinary ratio following administration of a solution that contained the two sugars. At the end of the study, the mean body weight of rats fed the low-iron diet was approx 95% that of the controls. The mean hemoglobin (g/dL) was significantly lower in the low-iron diet group (11.2±1.4) than in the control group (16.9±0.8) (p=0.001). The liver iron concentration (μg/g) of the anemic group (41.4±4.7) was also statistically (p=0.001) lower than in the control group (116.6±18.2). The lactulose/mannitol ratio was lower in the anemic rats (2.0±0.7) than in the control group (2.6±0.7) (p=0.008), a finding that is not suggestive of intestinal mucosal atrophy, previously described in anemic children.     

Improved carbohydrate tolerance in fibre-fed rats: studies of the chronic effect

The effect of chronic consumption of diets containing either different sources of dietary fibre (8% guar, 8% pectin, or 8% multifibre) or low carbohydrate upon carbohydrate tolerance was examined in rats. Weight gain was significantly lower throughout the entire 28-day study period with the guar group and after 20 days with the multifibre group. When tested with a liquid meal (1 g sucrose/kg body weight) after 14 days on the diets, only the guar rats had significantly lower fasting and postprandial plasma glucose concentrations. After 28 days, the improved carbohydrate tolerance persisted in the guar rats and started to appear in the multifibre rats. Pectin and low carbohydrate diets had no effect upon either weight gain or carbohydrate tolerance. Consuming the fibre diets did not affect jejunal sucrase activities. Jejunal glucose uptake activity was significantly diminished when measured in fasting guar rats while postprandially activities were similar to controls. Jejunal Na-K-ATPase activities in fasting and postprandial guar rats were not related to changes in glucose uptake. These studies confirm that only certain types of dietary fibre improve carbohydrate tolerance and suggest that reduced weight gain and altered intestinal glucose uptake are factors involved in the chronic fibre effect.     

乳果糖对严重烫伤大鼠白细胞介素-18介导的脏器功能的影响

目的：探讨乳果糖对烫伤大鼠白细胞介素-18 mRNA（IL-18 mRNA）介导的肺、肝、肾脏功能的影响。方法：将大鼠致30%体表面积Ⅲ度烫伤,随机分成2组（n=40）：对照组（C组）和乳果糖预防组（L组）。用改良的鲎试验基质显色法定量分析循环内毒素-脂多糖（LPS）含量;采用逆转录PCR技术检测肺、肝、肾组织中IL-18 mRNA水平;用改良的方法检测肺组织髓过氧化物酶（MPO）活性：使用7170型全自动生化分析仪测定血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、血清尿素氮（BUN）、血清肌酐（Cr）。结果：L组LPS含量伤后22、4 h显著低于C组（P〈0.05）;伤后C组各时点肺、肝、肾组织中IL-18 mRNA表达较伤前增强（P〈0.01）,伤后L组各脏器组织IL-18 mRNA表达明显低于C组（P〈0.05~0.01）;L组伤后81、6 h MPO活性显著低于C组（P〈0.05~0.01）;L组伤后2 h8、h1、6 h,ALT、AST、BUN、Cr明显低于C组（P〈0.05~0.01）。结论：烧伤早期循环LPS含量居高不下,肺、肝、肾等脏器IL-18 mRNA表达明显过度,其介导所致脏器的功能遭受严重损害,而经过乳果糖预处理可以在一定程度上保护肺、肝、肾等脏器功能。     

Lipid peroxidation and antioxidant systems in the blood of young rats subjected to chronic fluoride toxicity

Wistar albino rats were exposed to 30 or 100 ppm fluoride in drinking water during their fetal, weanling and post-weaning stages of life up to puberty. Extent of lipid peroxidation and response of the antioxidant systems in red blood cells and plasma to prolonged fluoride exposure were assessed in these rats in comparison to the control rats fed with permissible level (0.5 ppm) of fluoride. Rats treated with 100 ppm fluoride showed enhanced lipid peroxidation as evidenced by elevated malondialdehyde (MDA) levels in red blood cells but, 30 ppm fluoride did not cause any appreciable change in RBC MDA level. 30 ppm fluoride-intake resulted in increased levels of total and reduced glutathione in red blood cells and ascorbic acid in plasma while 100 ppm fluoride resulted in decreases in these levels. The activity of RBC glutathione peroxidase was elevated in both the fluoride-treated groups, more pronounced increase was seen with 100 ppm. Reduced to total glutathione ratio in RBC and uric acid levels in plasma decreased in both the groups. RBC superoxide dismutase activity decreased significantly on high-fluoride treatment. These results suggest that long-term high-fluoride intake at the early developing stages of life enhances oxidative stress in the blood, thereby disturbing the antioxidant defense of rats. Increased oxidative stress could be one of the mediating factors in the pathogenesis of toxic manifestations of fluoride.     

Mortality, body weight, food and water consumption, and clinical signs in F344/DuCrj rats in studies of chronic toxicity and carcinogenicity.

In vivo historical control data, including mortality, body weight, food and water consumption, and clinical signs in F344/DuCrj rats were obtained from 11 long-term toxicity and carcinogenicity studies conducted at the Biosafety Research Center, Foods, Drugs and Pesticides, (An-Pyo Center) during the last five years. Survival at 109 weeks of age was 80.2% (min: 74%, max: 90%) in males and 80.5% (min: 72%, max: 92%) in females. The maximum mean body weights of males and females were 443.3 +/- 15.8 g (mean +/- S. D.) and 295.7 +/- 13.3 g respectively. Male rats attained their maximum body weight at 82.6 +/- 5.3 weeks of age, the females at 103.5 +/- 2.5 weeks of age. Clinical symptoms increased with age, particularly after 84 weeks of age, and included: wasting, piloerection, palpable subcutaneous and abdominal masses, and decreased spontaneous movement. Lowered body temperature and auricular pallor occurred commonly in moribund animals. The nature and grade of toxicity in the treated animals were generally disclosed by comparing with the behavior and signs in the control animals. The use of in-house, historical control data can be useful in subsequent evaluations of chronic toxicity and carcinogenicity studies.     

Antiinflammatory and chronic toxicity study of the leaves of Ageratum conyzoides L. in rats

The hydroalcoholic extract (HAE) of Ageratum conyzoides leaves was studied for its antiinflammatory effect on subacute (cotton pellet-induced granuloma) and chronic (formaldehyde-induced arthritis) models of inflammation in rats. The absence or presence of toxicity by prolonged use of HAE was also evaluated through biochemical and hematological analysis of rats blood samples using daily oral doses of 250 or 500 mg/kg body wt., during 90 days. The results showed that the group of rats treated with HAE (250 mg/kg body wt.; p.o.) had a 38.7% (p < 0.05) reduction in cotton-pellet granuloma. The development of chronically induced paw edema was also reduced significantly (p < 0.05) by the plant extract. The toxicity study did not show any treatment-related abnormalities in biochemical and hematological parameters. The biochemical analysis from blood samples drawn from group of rats treated orally with 500 mg/kg body wt. did, however, present 30.2% (p < 0.05) reduction of SGPT activity as compared to the corresponding control group. These results confirm the antiinflammatory properties of A. conyzoides, with no apparent hepatotoxicity.     

Developmental toxicity of Citrus aurantium in rats

BACKGROUND: Ephedra was commonly used in herbal products marketed for weight loss until safety concerns forced its removal from products. Even before the ban, manufacturers had begun to replace ephedra with other compounds, including Citrus aurantium, or bitter orange. The major component in the bitter orange extract is synephrine which is chemically similar to ephedrine. The purpose of this study was to determine if relatively pure synephrine or synephrine present as a constituent of a bitter orange extract produced developmental toxicity in rats. METHOD: Sprague‐Dawley rats were dosed daily by gavage with one of several different doses of synephrine from one of two different extracts. Caffeine was added to some doses. Animals were sacrificed on GD 21, and fetuses were examined for the presence of various developmental toxic endpoints. RESULTS AND CONCLUSION: At doses up to 100 mg synephrine/kg body weight, there were no adverse effects on embryolethality, fetal weight, or incidences of gross, visceral, or skeletal abnormalities. There was a decrease in maternal weight at 50 mg synephrine/kg body weight when given as the 6% synephrine extract with 25 mg caffeine/kg body weight; there was also a decrease in maternal weight in the caffeine only group. This decrease in body weight may have been due to decreased food consumption which was also observed in these two groups. Overall, doses of up to 100 mg synephrine/kg body weight did not produce developmental toxicity in Sprague‐Dawley rats. Birth Defects Res (Part B) 92:216–223, 2011. © 2011 Wiley‐Liss, Inc.     

Acute toxicity of bisphenol A in rats

Bisphenol A (BPA), an estrogenic compound, is used in manufacturing plastics and is known to produce toxic effects on various systems in man and animals. Since the use of plastics in day-to-day life is increasing, exposure to BPA will also increase. Therefore, this study was undertaken to determine the median lethal dose (LD50) of BPA via intraperitoneal and intravenous route in adult rats (by Dixon's up and down method) and also to know the acute systemic changes (in blood pressure, respiration and ECG) produced by lethal dose of BPA. Adult female albino rats of Charles Foster strain were used in the study. LD50 of BPA was 841 and 35.26 mg/kg body weight for ip and iv route, respectively. Injection of lethal dose of BPA (40 mg/kg body weight) produced acute toxicity manifesting as immediate respiratory arrest and hypotension after the injection of BPA followed by bradycardia. The animals died within 7.3 +/- 0.7 min. Volume of ethanol (vehicle; 0.1 mL) present in the lethal dose of BPA was not lethal and had no effect on respiration, blood pressure and heart rate. The results provide evidence that the acute exposure to BPA produces lethality with a very narrow range of lethal and survival dose for iv route. Further, the lethality appears to be due to respiratory arrest and hypotension.