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Aim: to investigate the sub chronic toxicity of thiamethoxam on some parameters of reproductive performance in adult male rabbits including gene expression of LDH-C4, FSH? and LH? and GnRHR. Method: sixteen adult male Chinchilla rabbits were divided into two equal groups. Animals in the first group were treated orally with TMX at dose of 250 mg/kg body weight for 90 days. The second group was served as control. Result: Obtained results showed that TMX increased the relative weight of some reproductive organs including testis and prostate. Hormonal analysis revealed that, TMX induced a significant elevation in the serum testosterone level, while the concentrations of FSH and LH hormones did not exhibit any alterations between treated and control groups. In addition, LDH-C4, FSH? and LH? and GnRHR genes were down regulated in TMX treated group. Conclusion: Administration of thiamethoxam for 90 days in male rabbits induced a noticeable adverse effect on serum testosterone level and down regulated genes related to male rabbit reproductive performance
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Objective@#The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake.@*Methods@#DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD.@*Results@#Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.@*Conclusion@#The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.
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Animals , Rats , Body Weight , Organ Size , Pyrones , Rats, Sprague-DawleyABSTRACT
Background: Chromium, an essential trace mineral plays an important role in the metabolism of carbohydrate, fat and proteins. Chromium picolinate (Cr.Pic) is used in alternative medicine to treat chromium deficiency. Though Cr.Pic is increasingly used to treat diabetes and obesity, studies on its safety profile is limited.Methods: Acute toxicity study was conducted by oral administration of Cr.Pic (2000 mg/kg body weight). The animals were maintained another 14 days with once a day observation. For sub-chronic studies, test groups were treated with Cr.Pic 10 mg/kg/day for 90 days. Tests for hepatic and renal function were conducted. Effect of Cr.Pic on behavioural changes and motor co-ordination was done on every week. Histopathological studies were conducted on day 90 at the end of the experiment.Results: Acute toxicity study of Cr.Pic showed no signs of toxicity and mortality. Absence of any behavioural alteration or mortality during the period of 14 days indicates that Cr.Pic has no latent effect. Similar results were obtained with sub-chronic studies suggesting safety of Cr.Pic. Cr.Pic treated groups showed no changes in learning and motor co-ordination compared to the untreated group. No gross histopathological changes were seen in any group indicating safety of Cr.Pic.Conclusions: The present study conferred safety profile of Cr.Pic from normal results obtained in hepatic function, renal function, behavioural and histopathological studies, suggesting its safety.
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This study evaluated the acute and sub-chronic toxicities of ethanol leaf extract of Dryopteris filix-mas. Acute toxicity and phytochemical tests on ethanol leaf extract were determined. In sub-chronic toxicity test, animals were treated with 62.5, 125, 250 and 500 mg/kg of extract every day for 90 days. Blood samples were collected via retro-orbital puncture for baseline studies and at 31, 61 and 91st days for determination of hematological, kidney and liver function parameters. Liver and kidneys were harvested for histopathology analyses on 91st day. Also, a 28 day recovery study was carried out to determine reversibility in toxicological effects. Phytochemical screening revealed the presence of tannins, phenols, flavonoids, saponins, steroids, alkaloids, terpenoids, reducing sugar and cardiac glycosides. Acute toxicity test did not show toxicity or death at 5000 mg/kg. There was significant (p<0.005) reduction in white blood cell and lymphocyte counts, significant (p<0.05) increase in some liver and kidney biomarkers as well as alterations in liver and kidney histo-architecture on 91st days in animals that were treated with 250 and 500 mg/kg extract. However, toxicities observed on 91st day were reversible in recovery studies. The leaf extract of Dryopteris filix-mas may be hepatotoxic and nephrotoxic when used for long periods
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Animals , Male , Female , Rats , Plant Extracts/analysis , /adverse effects , Dryopteris/toxicity , Toxicity Tests, Subchronic/instrumentation , Ethanol/toxicityABSTRACT
OBJECTIVE@#To explore the possible long-term health effects of the defoamer used in seawater desalination by sub-chronic toxicity testing.@*METHODS@#Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high (0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration.@*RESULTS@#The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase (P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin (P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups (P < 0.05). All dose groups showed significant induction of alkaline phosphatase (P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices.@*CONCLUSION@#Long-term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.
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Animals , Female , Male , Administration, Oral , Antifoaming Agents , Toxicity , Blood Chemical Analysis , Body Weight , Eating , Rats, Wistar , Toxicity Tests, SubchronicABSTRACT
Objective: Realgar–Indigo Naturalis formula (RIF) is a well-known arsenic-containing preparation that is used to treat acute promyelocytic leukemia (APL) in China. In recent multicenter clinical trials, complete remission rates in APL patients have ranged from 96.08% to 100%. RIF has a satisfactory therapeutic effect, but its safety is a widespread concern, since the preparation contains arsenic, a wide-ranging and naturally occurring toxicant. In this study, in order to determine the toxic potential of RIF, acute toxicity and sub chronic toxicity assays were performed to evaluate the toxic potential of Realgar and the adjuvant components of RIF in addition to Realgar's synergy with these adjuvant components. Methods: KM mice and Wistar rats were selected for these experiments. To evaluate acute toxicity, the toxic effects of a single dose of a gradient of concentrations of Realgar were firstly determined. Then, the toxic effects of combinations of gradient doses of Realgar and fixed doses of Indigo naturalis and Salvia miltiorrhiza were evaluated. Results: The results showed that when Realgar was used alone, the LD50 was 2756.73 mg/kg (equivalent to 23.6 mg/kg As2O3). However, the LD50 dropped to 936.90 mg/kg when Realgarwas used with I. naturalis. By contrast, the LD50 increased to 7538.86 mg/kg when Realgar was used with S. miltiorrhiza. Hence, I. naturalis strengthened the toxicity of Realgar, whereas S. miltiorrhiza displayed the opposite effect. The sub chronic toxicity assessment results revealed a trend that was consistent with acute toxicity. Changes in the levels of different valence states of arsenic were also taken into account. The test results of the effects of in vitro combinations of Realgar and adjuvant components on soluble arsenic dissolution showed that I. naturalis increased the level of soluble arsenic in Realgar extracts and I. naturalis suspensions when theRealgar/I. naturalis ratio was 2, 1.5, and 1.0. However, S. miltiorrhiza did not affect it. Conclusion: Based on the collective experimental results presented here, it can be concluded that the toxicity of RIF is the result of the soluble arsenic in Realgar and that the I. naturalis and S. miltiorrhiza in the RIF exert completely opposite effects on the toxicity of Realgar. This maybe an intelligent explanation for the compatibility of this formula, and this RIF study may therefore be viewed as a classic case of traditional Chinese medicine research on compatibility.
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Objective To evaluate the repeated dose toxicity of MNT-016 in SD rats and to provide reference for toxicity evaluation.Methods MNT-016 was administered to rats at 5, 20 and 80 mg/kg for 90 days.The toxic effects on the animals were evaluated by observing the clinical signs and measuring the body weight, hematology and blood biochemistry as well as histopathological examination.NOAEL and benchmark dose lower confidence limit(BMDL) were observed by the end point of toxicity.Results Compared with the control group, the AST, TBIL, DBIL and Crea of male rats were increased in a dose-dependent manner, while TG and CHOL decreased.The body mass(before anatomy), heart, liver, thymus, epididymis of male rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of the heart and lung was increased.The body mass (before anatomy) and thymus of female rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of lungs was increased.Vacuolation of hepatocytes was observed in groups each dose, tubule atrophy was found in the kidneys of 20 and 5 mg/kg groups, and tubule basophilia was observed in 80 mg/kg group.The incidence of the above lesions was higher in male animals than in female ones.Conclusion The NOAEL of MNT-016 is lower than 5 mg/kg in male rats and 5 mg/kg in female rats.BMDL value is 2.65 mg/kg in male animals and more accurate than NOAEL, and is 9.04 mg/kg in female animals,which is slightly larger than the corresponding NOAEL.
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OBJECTIVE: To explore the sub-chronic oral toxicity of 1,1-diamino-2,2-dinitroethene( FOX-7) in rats.METHODS: Ninety-six specific pathogen free healthy adult SD rats were randomly divided into control group,low-,medium-,and high-dose groups. Each group consisted of 24 rats,half of them were males and the other half were females.The low-,medium-,and high-dose groups of rats were exposed to 10,30,90 mg /( kg·d) body weigh of 1,1-diamino-2,2-dinitroethene by gavage for 90 days,once a day,6 days a week. The control group was given the same volume of 4%water starch solution. The toxic symptoms,the body weight,food utilization,routine blood,blood biochemical indicators,organ coefficients and histopathology changes of the rats were observed or tested. RESULTS: a) The body weights of male and female rats in the high-dose group in the 28 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). Food utilization in the male and female high-dose group in the 77 th and 90 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). b) Red blood cell counts,hemoglobin levels,hematocrit levels in the female rats of low-,medium-,and high-dose groups were lower than those of the female control group( P < 0. 05). Platelet counts in the female high-dose group was lower than that of the female control group( P < 0. 05). Red blood cell counts,hemoglobin level,hematocrit level and mean corpuscular hemoglobin concentration in the male high-dose group were lower than those of the male control group( P < 0. 05). The platelet counts in the male medium-,and high-dose group were lower than that of the male control group( P < 0. 05). c) Total cholesterol levels in female medium-,and high-dose group and blood urea nitrogen level in the female high-dose group were higher than those of the female control group( P < 0. 05). In high-dose group,the levels of total protein and uric acid were higher and lactate dehydrogenase level was lower than those of the control group( P < 0. 05). d) The spleen organ coefficients in the female high-dose group were higher and those in male medium- and high-dose groups were higher than those of the control group for same sex( P < 0. 05). The organ coefficients of liver and kidney in high-dose group were higher than those of the control group( P < 0. 05),the organ coefficients of testis and epididym in the male high-dose group were lower than those of the male control group( P < 0. 05). The testis convoluted tubule shrink and seminiferous cells decreased in the male high-dose group. e) The no observed adverse effect level of FOX-7 dinitroethene in female rats were less than10. 00 mg /( kg·d) and it was 10. 00 mg /( kg·d) in the male rats. CONCLUSION: FOX-7 could inhibit the growth of rats and damage the blood system and male reproductive system.
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OBJECTIVE@#To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety.@*METHODS@#Acute toxicity was determined by oral administration of a single dose of 18100 mg/kg forsythin in NIH mice. Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0, 540, 1620, and 6480 mg/kg in SD rats.@*RESULTS@#In the acute toxicity study, mortality was not observed after 14 days. In addition, clinically relevant adverse effects, or variations in body weight or food consumption were not observed. Similarly, after 30 days in the sub-chronic toxicity study, no mortality or significant toxicological effects such as decreased food consumption, body weight, biochemical parameters and vital organs etc. were noticed.@*CONCLUSION@#The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration, and therefore is suitable for further development and applications.
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Objective To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety. Methods Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice. Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0, 540, 1 620, and 6 480 mg/kg in SD rats. Results In the acute toxicity study, mortality was not observed after 14 days. In addition, clinically relevant adverse effects, or variations in body weight or food consumption were not observed. Similarly, after 30 days in the sub-chronic toxicity study, no mortality or significant toxicological effects such as decreased food consumption, body weight, biochemical parameters and vital organs etc. were noticed. Conclusion The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration, and therefore is suitable for further development and applications.
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ABSTRACT Spinosad (SPD) is a highly selective insect control product. However, it was reported that SPD has toxicity toward other non-target organisms. This study was conducted to address the toxic effect of two sub-chronic low and high doses; 35 and 350 mg/kg SPD on some biochemical, histological and immunohistochemical parameters of the liver, kidney and cerebellum. Thirty-six male Swiss mice were divided into three groups of 12 mice each; first group (G1) served as a control, second group (G2) received a low sub-chronic dose of SPD that is equal to 35 mg/kg, and third group (G3) received a high sub-chronic dose of SPD that is equal to 350 mg/kg. The results showed that mice which were received 350 mg/kg SPD showed a significant decrease in the body weight and a significant increase in their relative kidney and spleen weights. They also showed a significant increase in alanine aminotransferase (ALT), triglycerides and urea levels. Histopathological examination showed cytoplasmic degeneration and cell necrosis in the liver and kidney. Immunohistochemical examination showed that cerebellum illustrated several neurodegenerative changes and a down-regulation of synaptophysin-Syp. In conclusion, exposure to a high dose of SPD that is equal to 350 mg/kg could cause a marked toxicity on the liver, kidney and cerebellum in male albino mice.
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The possible protective effects of the ethyl acetate fraction of Solanum erianthum ethanol leaf extract on lead-induced toxicity in adult Wistar rats were investigated. Phytochemical constituents, antioxidant and membrane stabilizing activities of the ethanol extract and its fractions were determined using standard procedures. Acute and sub-chronic oral toxicity studies were carried out. The rats were treated orally with lead (10 mg/kg b. wt) and extract (100 mg/kg b. wt). The blood samples, liver, and kidney were collected for the estimation of biochemical and organ parameters, and histomorphological studies. The ethyl acetate fraction had the highest antioxidant activities and high membrane stabilizing potentials when compared to the crude extract and other fractions. Significant elevations were observed in plasma albumin, creatinine and urea levels in group treated with lead only. The activities of plasma ALT and AST were significantly increased in group treated with lead alone. Treatment with ethyl acetate fraction significantly decreased (p < 0.05) the elevated ALT, AST, urea and creatinine levels. The histology evidence showed progressive degeneration of the liver and kidney tissues in lead treated groups while the administration of S. erianthum showed appreciable degrees of protection to both the liver and kidney. The study concluded that ethyl acetate fraction of S. erianthum has protective effects against lead-induced toxicity in adult Wistar rats.
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ABSTRACT The genus Aconitum has strong toxicity, but the acute toxicity of baked Aconitum flavum Hand.-Mazz., Ranunculaceae, was reduced significantly on the premise of keeping anti-inflammatory and anti-nociceptive activities. However, the risk associated with long-term use is unknown. In a sub-chronic toxicity study, rats were orally administered A. flavum at doses of 0.76–3.03 g/kg for 90 days and further recovered for 14 days. Our results showed that oral treatment with A. flavum for 90 days caused significant changes in some hematological indicators at doses of 3.03 and 1.52 g/kg, such as red blood cell, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. These results indicated that the A. flavum affects the structure and function of red blood cell. Furthermore, significant changes were observed in the white blood cell at dose of 3.03 g/kg in male rats, which confirmed tissue damage or toxicity. The liver function tests exhibited non-significant alterations in aspertate aminotransferase, alanine aminotransferase and avenin-like storage proteinsgene. But other parameters, such as total protein and albumin were obviously decreased at all doses. A. flavum also caused a significant decrease in glucose, cholesterol and triacylglyceride at all doses. For kidney function, there were significant elevations in urea and creatinine at doses of 3.03 and 1.52 g/kg. The levels of certain electrolytes (Na+, K+ and Cl-) were significantly different after 90 days of treatment with A. flavum (3.03 and 1.52 g/kg). Organs were observed by light microscopy after hematoxylin-eosin staining. Hemosiderin depositions in the spleen were observed in the A. flavum group. These data demonstrated that the subtoxicity of A. flavum was reduced considerably by baked, but the subchronic toxicity effects on the liver, kidney and spleen should not be ignored.
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<p><b>OBJECTIVE</b>To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine (TET) in female BALB/c mice.</p><p><b>METHODS</b>The median lethal dose (LD) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET (30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period.</p><p><b>RESULT</b>LDwas found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically signifificant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET (P >0.05). In the sub-acute toxicity study, no signifificant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group (P >0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions.</p><p><b>CONCLUSIONS</b>The overall fifindings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.</p>
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Animals , Female , Administration, Intravenous , Benzylisoquinolines , Toxicity , Body Weight , Mice, Inbred BALB C , Organ Specificity , Toxicity Tests, Acute , Toxicity Tests, ChronicABSTRACT
The present study was aimed to explore the acute and sub chronic toxicity studies with orally administered ethanolic leave extract of Epipremnum aureum. For the acute toxicity study, the animals were divided into four groups and each group receives a dose of (50, 500, 2000) mg/kg except control group which receives only 1% CMC. They were observed for 14days for signs of toxicity. In case of sub chronic toxicity, the Sprague dawley rats were fed with ethanol extract (100, 600, and 1000) mg/kg per day for 28 days. The parameters measured include organ weight, biochemical test, haematological test and histopathological observations. Acute oral administration of Epipremnum aureum did not show any mortality, CNS and ANS toxicities. Similarly in subchronic toxicity studies, Epipremnum aureum did not show any visible signs of toxicity. There were also no significant differences between the control and extract treated groups in terms of their organ weight, haematological and biochemical parameters. Histopathological examination did not reveal any remarkable and treatment related changes. A no-observed adverse-effect level for extract is 2000 mg/kg for rats under the conditions of this study. Hence, the extracts could be considered safe at the doses administered since they did not provoke toxic effect on the key organs examined and also did not alter any biochemical and haematological parameters.
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Background: Polyscias fruticosa is been used in Ghanaian folkloric medicine for the management of asthma and its related complications. Aim: This study evaluated the muco-suppressant, anti-tussive, and safety profile of an ethanolic leaf extract of Polyscias fruticosa in its use as an anti-asthmatic. Place and Duration of Study: Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, KNUST, Kumasi, Ghana and the School of Physical Sciences, University of Cape-Coast, Cape-Coast, Ghana; between December, 2013 and May, 2014. Methodology: Preliminary phytochemical screening was carried out on the extract. Ammonium chloride-induced tracheal mucus phenol red secretion in ICR mice and the suppression of citric acid-induced cough in Dunkin-Hartley guinea pigs were determined after treatment of experimental animals with 100 mg/kg sodium cromoglycate, or 20 mg/kg dihydrocodeine respectively, as well as with 100, 250, or 500 mg/kg of the extract. A 100, 250, and 500 mg/kg dose of the extract was administered daily for 28 days to groups of guinea pigs to establish a safety profile in a sub-chronic toxicity study. Results: Phytochemical screening revealed the presence of saponins and cyanogenetic glycosides, alkaloids, and sterols. The extract significantly inhibited (P ≤ .01 - 0.001) tracheal mucus phenol red secretion, and suppression of citric acid-induced cough. There were no significant changes in body weight, haematological profile, as well as liver and kidney functions in the sub-chronic toxicity study. Conclusion: The findings indicate that the ethanolic leaf extract of Polyscias fruticosa has muco-suppressant and anti-tussive properties, and is safe to use; hence a suitable adjunct/remedy for the management of asthma.
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Ricinus communis seed has been proven effective to prevent conception since time immemorial. This research focuses on the toxicity study of the seed suspension in Wister albino rats. Twenty four (24) rats were used for the sub-chronic toxicity study, while 13 mice for the acute toxicity study. The seed suspension of Ricinus communis seed at three graded concentrations (3.80, 7.60 and 11.40 mg/kg body weight) was administered orally; to Groups I, II and III respectively once every day for the period of one month. The liver and kidney functions were determined after the last administration. Serum alanine amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine were determined. The activity of ALT, AST, ALP and the concentrations of urea and creatinine at 3.80 mg/kg body weight showed no significant difference (p>0.05) compared to the control. However, a significant increase (p<0.05) in these parameters was observed in rats given 7.60 and 11.40 mg/kg body weight. Similarly a significant increase (p<0.05) in lipid profile was observed in rats given 11.40 mg/kg body weight. Acute toxicity revealed the median lethal dose (LD50) of 1587 mg. Histological analysis of the liver and kidneys of the rats after three months revealed no cellular death, necrosis or inflammation. This indicates that consecutive use of the seed at the traditional dose (3.80 mg/kg in rat; equivalent to 3 seed/70Kg in human) for long period of time is neither hepatotoxic nor nephrotoxic. Ricinus communis seed is therefore safe in rats at the concentrations administered.
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Objective To study the effect of sub-chronic exposure to deltamethrin(DM) on the behavior of mice in learning and memory and expression of GABAA receptor α1 and γ2 subunits in the hippocampus of mice.Methods 60 female SPF Kunming mice were randomly divided into solvent control group,low-dose group,middle-dose group and high-dose group, 15 mice in each group.The latter three groups were exposured to deltamethrin for 60 days by gavage.Open field test (OFT) was applied to evaluate locomotor activity and exploratory behavior in mice.RQ-PCR was employed to measure the expression of GABAA receptor α1 and γ2 subunits in hippocampus of mice.Results After exposure to DM,the moving distance of the central area in the middle-dose group ((555.1 ± 12.8) cm) and high-dose group ((516.4± 11.88) cm) was significantly higher than that in the solvent control group ((327.3± 117.8) cm, P＜0.05).Numbers of standing in marginal area (F=4.117, P=0.010) and total movement distance (F=2.914, P=0.042) in the high-dose group ((27.9±9.9) times, (3211.3±379.8) cm) were also significantly higher than that in the solvent control group ((15.1 ±8.9)times, (3211.3±379.8)cm).The expression of GABAA receptor α1 subunit mRNA in the middle-dose group and high-dose group was significantly lower than that in the low-dose group and solvent control group(F=8.508, P=0.001) and the expression of GABAA receptor γ2 subunit mRNA in high-dose group was significantly lower than that in the other groups (F=6.738, P=0.002).Conclusion Sub-chronic exposure to DM can damage the function of locomotor activity and exploratory behavior,and inhibit the expression of GABAA receptor α1 and γ2 subunits in the hippocampus of mice.
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The acute and sub-chronic toxicities of ulcer fast® (UF) - A commercial bi-herbal formula prepared with Alstonia boonei and Xylopia aethiopica in male Wistar albino rats was evaluated. There was no mortality in rats administered 2000 mg/kg body weight (BW) of UF in an acute toxicity study. A significant (p≤0.05) increase in daily consumption of feed and fluid intake in experimental rats after 28 days was recorded followed by a progressive increase in BW of rats administered 50, 100 and 200 mg/kg BW of UF in a dose-dependent manner. Alanine amino transferase, aspartate amino transferase, alkaline phosphatase, lactate dehydrogenase, triacylglycerides and creatinine increased significantly (p≤0.05) in rats treated with UF, whereas urea and fasting blood sugar decreased significantly (p≤0.05) in a dose-dependent manner when compared with control. There was a marginal decrease in serum calcium ion and phosphate ion following the administration of UF when compared with control. Packed cell volume and hemoglobin decreased significantly (p≤0.05) in rats treated with UF, whereas white blood cell increased significantly (p≤0.05) in a dose-dependent manner when compared with control. Histological examination of the liver, kidney, heart and lungs showed normal architecture in control group, whereas hepatocytes of rats treated with 50, 100 and 200 mg/kg BW of UF were characterized by slight periportal fatty change, marked change and ballooning degeneration. Heart muscle of rats treated with 200mg/kg BW of UF showed slight inflammation while histological examination of the lungs showed areas of interstitium damage and diffuse alveolar damage in rats treated with UF. In conclusion, indiscriminate administration of UF could be of public health concern and long-term exposure may cause a significant potential health risk.
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This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.