Subacute Toxicity Profile of Lacidipine Nanoformulation in Wistar Rats.
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ABSTRACT:
SUBMITTER: Shirodkar R
PROVIDER: S-EPMC4458540 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Syringic acid (SA) is a phenolic acid and have been investigated for diverse pharmacological activities, but the safety and/or mechanism of toxicity is still lacking in the literature. Subacute toxicity studies will add value to its pharmacological profile and support its exploration as a future medicine. According to OECD TG 407 (OECD, 2008), rats were divided into 3 groups (n = 12). The dose of SA was decided by limit test. Treatment and satellite groups received SA (1000 mg/kg/day, p.o for 14 days), whereas an equal volume of vehicle was given to control groups. In order to access reversibility, satellite groups were kept for another 14 days post-treatment. The toxic signs, mortality and body weight changes were recorded. On day 15 and 29 the rats were anesthetized to collect blood for estimation of hematological and biochemical parameters and then sacrificed to collect internal body organ for weighing and histopathological studies. SA has no major adverse effect on the body weight, food intake, erythropoiesis, leucopoiesis and on internal body organs which was confirmed by evaluating various biochemical and hematological parameters, relative body organ weight and histopathological studies. Therefore, SA could be considered safe over limited period of time and this study may help researchers in establishing the doses for the longer-term subchronic studies. Further, subchronic and chronic toxicity studies are required to evaluate safety on long term use.
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Project description:Recent adverse herb reactions have stimulated interest documenting the safety profile of medicinal agents. Thus, subacute and subchronic oral toxicity of the hydroethanolic extract of Acridocarpus smeathmannii root (HEASR) in Wistar rats was investigated. In the 28 and 90-day subacute and subchronic toxicity tests, sixty-four rats (n = male: female = 1:1 = 32) were divided into four of eight/group and ninety-six (n = male: female = 1:1 = 48) into twelve/group respectively. Distilled water (10 mL/kg) or HEASR4, HEASR5 and HEASR6 (250, 500 and 1000 mg/kg/day) respectively were administered via oral gavage. Animals were killed humanely 24 h after the last administration. Using standard methods, acute oral toxicity dose of HEAR (2000 mg/kg) was non-lethal in rodents. Subacute administration of HEASR6 increased total bilirubin (p < 0.05) in female rats. HEASR moderately altered both haematological and biochemical indices in rats. HEASR6 administration reduced ovary weight in both studies while follicle stimulating hormone level in male was reduced at all doses used. HEASR modulated lipid peroxidation, sperm quality and elevated cyclooxygenase-2 levels in rats. Histology revealed gastritis and congestions in vital organs. The low-observed adverse effect level for HEASR was below 250 mg/kg for both sexes. Overall, HEASR demonstrated inherent toxicity evidenced by our current findings. The exaggeration of its folklore medicine applications calls for cautions.
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Project description:The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. For insight into early mechanisms of non-genotoxoc carcinogenesis and for identification of potential early biomarkers of non-genotoxic carcinogenesis, groups of rats were treated with a range of known non-genotoxic carcinogens for a period of 14, 28, or 90 days, and liver tissue was harvested for expression profiling. Control groups were treated with appropriate vehicles.
2018-04-20 | GSE68128 | GEO
Project description:ObjectiveThe objective of this study was to observe the effects of chronic dosing with monosodium glutamate on mortality, fertility, major organ functions and histology in albino Wistar rats.Results6 male and 6 female rats (age 6 weeks) were bred in a cage, feeding on standard growers' mash, with monosodium glutamate added (120 mg/kg/day). 12 corresponding breeding rats (on standard feed without MSG) were controls. Chronic dosing with monosodium glutamate in albino Wistar rats (at a dose consistent with the human ADI) led to increased mortality, fertility impairment, and significant changes in major organ function tests and histology. 23 deaths were recorded in the rats fed with MSG additive, while mortality was zero in the control animals. Fertility was lower in rats on MSG (48 births) than in controls (117 births). The weight gain of the MSG rats was higher than in controls. Biochemical parameters and organ histology remained normal in control animals. In MSG-treated rats however, liver/renal function tests, fasting serum cholesterol and triglyceride, serum uric acid showed a significant rise at trimestrial time-points. Histology showed mild portal inflammation in MSG rats, with periglomerular fibrosis and interstitial nephritis in two rats, at 6-12 months.
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Project description:Azaspiracids (AZAs) are marine toxins produced by Azadinium spinosum that get accumulated in filter feeding shellfish through the food-web. The first intoxication was described in The Netherlands in 1990, and since then several episodes have been reported worldwide. Azaspiracid-1, AZA-2, and AZA-3 presence in shellfish is regulated by food safety authorities of several countries to protect human health. Azaspiracids have been related to widespread organ damage, tumorogenic properties and acute heart rhythm alterations in vivo but the mechanism of action remains unknown. Azaspiracid toxicity kinetics in vivo and in vitro suggests accumulative effects. We studied subacute cardiotoxicity in vivo after repeated exposure to AZA-1 by evaluation of the ECG, arterial blood pressure, plasmatic heart damage biomarkers, and myocardium structure and ultrastructure. Our results showed that four administrations of AZA-1 along 15 days caused functional signs of heart failure and structural heart alterations in rats at doses ranging from 1 to 55 µg/kg. Azaspiracid-1 altered arterial blood pressure, tissue inhibitors of metalloproteinase-1 plasma levels, heart collagen deposition, and ultrastructure of the myocardium. Overall, these data indicate that repeated exposure to low amounts of AZA-1 causes cardiotoxicity, at doses that do not induce signs of other organic system toxicity. Remarkably, human exposure to AZAs considering current regulatory limits of these toxins may be dangerously close to clearly cardiotoxic doses in rats. These findings should be considered when human risk is estimated particularly in high cardiovascular risk subpopulations.
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Project description:Background:Combretum micranthum (CM) (Combretaceae) is widely used in traditional medicine throughout West Africa for the treatment of diabetes, hypertension, inflammation, malaria and liver ailments. In our recent research we demonstrated that CM has nephroprotective potentials in diabetes mellitus, hypertension and renal disorders. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported. Aim of the study:The study carried out to evaluates the potential toxicity of the hydroalcoholic extract from leaves of the CM, through the method of acute and sub-chronic oral administration in rats. Materials and methods:During the acute toxicity study, male and female rats were orally administrated with CM extract at single doses of 5000 mg/kg (n = 5/group/sex). Abnormal behaviour, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. For sub-chronic toxicity study, the extract was administered orally at doses of 500 and 1000 mg/kg (n = 5/group/sex) daily to Wistar rats for 28 days. The general behaviour and body weight of the rats was observed daily. A biochemical, haematological, macroscopical and histopathological examinations of several organs were conducted at the end of the treatment period. The CM extract was subjected to Fourier transform infrared spectrophotometric examination in order to detect the presence or absence of cyanide toxic compounds. Results:The absence of absorbance peaks between the 2220-2260 cm-1 region of FT-IR spectrum of CM, indicating the absence of cyanide groups. This suggested that the CM extract may not contain toxic substances. During the acute toxicity test, no mortality or adverse effects were noted at the dose of 5000 mg/kg. In the subchronic study, the CM extract induced no mortality or treatment-related adverse effects with regard to body weight, general behaviour, relative organ weights, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations. Conclusion:The present study revealed that oral administration of CM extract for 28 days, at dosage up to 1000 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the extract was estimated to be more than 5000 mg/kg.
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Project description:Background:Ursolic acid (UA) has been used in alternative medicine for decades, and there has been a great interest in its medicinal properties. Despite this increased interest, a detailed long-term toxicity study has not been performed. The objective of this study was to determine the long-term toxic effect of UA on clinical chemistry, haematology, coagulation, pathology/morphology, behaviour and motor skills in rats. Methods:A solution was made by dissolving UA in a mixture of 0.1% Tween 80 and 0.5% hydroxypropyl methylcellulose in Milli-Q Water. The control group received the vehicle, and the test groups received a dose up to 1000?mg/kg/day via oral gavage. The solution was administered to both male and female (Han-Wistar) rats for 90 consecutive days. Results:UA did not cause any deaths, abnormal body weights or abnormal pathology at all test doses. In addition to that, no toxicological changes were observed in behaviour, neurotoxicity, coagulation, haematology or clinical chemistry that are related to the administration of UA. Conclusion:This study indicates that oral dosing of UA for 90 consecutive days does not lead to toxic effects at any of the doses. Therefore, the NOAEL for UA is likely to be higher than 1000?mg/kg/day.
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Project description:BackgroundCs2K4Na [SiW9Nb3O40] (POM93) is a novel broad-spectrum antiviral agent with high activity, high stability, and low toxicity in vitro. Most toxicity studies for POM93 have been performed in cultured cell lines rather than in animals. Like other POMs, there is a lack of evidence for in vivo toxicity limits, oral bioavailability, and therapeutic applications.MethodsThe toxic properties of POM93 were evaluated comprehensively in vivo, including the acute and subchronic oral toxicity studies and genotoxicity tests.ResultsThe acute toxicity study showed no abnormal changes or mortality in rats treated with POM93 even at the single high dose of 5000 mg/kg body weight. In the subchronic toxicity study, regardless of the body weight, the organ weight, and the hematological parameters, similar results were observed between the control group and the experimental groups. POM93 produced mild changes in rare hematological parameters in the liver and kidneys, but did not induce the clinical symptoms of liver or kidneys injury in rats as confirmed by histopathological analysis. Moreover, neither mutagenicity nor clastogenicity was caused by POM93 treatment in vitro and in vivo.ConclusionsThe present study demonstrates that the oral administration of POM93 is presumed safe and poses a low risk of potential health risks.
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