Acute and Subchronic Toxicity Studies of Aristolochic Acid A in Tianfu Broilers.
Ontology highlight
ABSTRACT:
SUBMITTER: Xu D
PROVIDER: S-EPMC8228413 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Aristolochic acid (AA) is a component of traditional Chinese herbs and commonly used for farm animals in China. Over-exposure of AA has been proven to be associated with hepatotoxicity; however, the mechanism of action of AA-I-induced hepatotoxicity remains unknown. In the current study, a subchronic toxicity test was conducted to evaluate the mechanism of AA-induced hepatotoxicity in Tianfu broilers. According to the results, AA-I-induced hepatotoxicity in Tianfu broilers was evidenced by the elevation of liver weight, levels of serum glutamic oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). Furthermore, hepatocyte swelling, vesicular degeneration and steatosis were observed. Additionally, AA-I elevated the production of reactive oxygen species (ROS) and induced oxidative stress, which further led to excessive apoptosis, characterized by mitochondrial depolarization, upregulation of Bax, and down-regulation of Bcl-2 expression. In conclusion, the mechanism of AA-I-induced hepatotoxicity was associated with oxidative-stress-mediated apoptosis and mitochondrial damage.
| S-EPMC8698099 | biostudies-literature
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.
| S-EPMC5382445 | biostudies-literature
Project description:Lipopolysaccharide (LPS) is an endotoxin that can cause an imbalance between the oxidation and antioxidant defense systems and then induces hepatic damages. Ferulic acid (FA) has multiple biological functions including antibacterial and antioxidant activities; however, the effect of FA on lipopolysaccharide-induced hepatic injury remains unknown. The purpose of this study was to investigate the mechanism of action of dietary Ferulic acid against Lipopolysaccharide-induced hepatic injuries in Tianfu broiler chickens. The results showed that supplementation of FA in daily feed increased body weight (BW) and decreased the feed conversion ratio (FCR) in LPS treatment broilers significantly (p < 0.05). Additionally, supplement of FA alleviated histological changes and apoptosis of hepatocytes in LPS treatment broilers. Supplement of FA significantly decreases the activities of ROS. Interestingly, the levels of antioxidant parameters including total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and glutathione (GSH) in LPS group were significantly increased by the FA supplementation (p < 0.05). Nevertheless, administration of LPS to broilers decreased the expressions of Nrf2, NQO1, SOD, GSH-Px, CAT and Bcl-2, whereas it increased the expressions of Bax and Caspase-3 (p < 0.05). Moreover, the expressions of Nrf2, NQO1, SOD, CAT, Bcl-2 were significantly upregulated and Caspase-3 were significantly downregulated in the FL group when compared to LPS group (p < 0.05). In conclusion, supplementation of FA in daily feed improves growth performance and alleviates LPS-induced oxidative stress, histopathologic changes, and apoptosis of hepatocytes in Tianfu broilers.
| S-EPMC8955363 | biostudies-literature
Project description:In the present study, goal was to scan the potential biomarker for acute kidney injury induced by aristolochic acid I (AAI).We utilized the microarry analysis to investigate the microRNA (miRNA) expression profile in kidneys from rat treated by 40mg/kg AA I for 2-6 days. miRNAs with significantly different expression of global miRNA expression profile were validated by qRT-PCR. For miRNAs still significantly disregulation, we further examined the expression in plasma of rats treated with AAI dosed at 10, 20 and 40mg/kg AAI for 2-6 days by qRT-PCR. miRNAs with significantly dysregulation in plasma, their expression in brain, liver and heart was examined for kicking out the non-specific disregulation in AAI induced acute kidney injury, so that the significant dysregulation miRNAs with specificity in kidney and plasma was found as potential biomarkers for AAI induced acute kidney injury.
2016-03-10 | GSE79063 | GEO
Project description:In the present study, goal was to scan the potential biomarker for acute kidney injury induced by aristolochic acid I (AAI).We utilized the microarry analysis to investigate the microRNA (miRNA) expression profile in kidneys from rat treated by 40mg/kg AA I for 2-6 days. miRNAs with significantly different expression of global miRNA expression profile were validated by qRT-PCR. For miRNAs still significantly disregulation, we further examined the expression in plasma of rats treated with AAI dosed at 10, 20 and 40mg/kg AAI for 2-6 days by qRT-PCR. miRNAs with significantly dysregulation in plasma, their expression in brain, liver and heart was examined for kicking out the non-specific disregulation in AAI induced acute kidney injury, so that the significant dysregulation miRNAs with specificity in kidney and plasma was found as potential biomarkers for AAI induced acute kidney injury. Five control and 15 kidneys treated with 40mg/kg AAI on day 2, 4 and 6 was examined by microarray.
2016-03-10 | E-GEOD-79063 | biostudies-arrayexpress
Project description:BackgroundThe possible toxicity of natural products must be tested before being used in the market. The present work aimed to evaluate acute, subacute, and subchronic toxicity of an herbal formulation containing Anethum graveolens, Cynara scolymus, Citrus aurantium, Portulaca oleracea, and Silybum marianum.Material and methodsAcute toxicity (2000 mg/kg, single dose) and sub-acute toxicity (600 and 1200 mg/kg/day, 4 weeks) tests were performed on female and male rats according to OECD 423 and OECD 407 guidelines, respectively. In the subchronic study (12 weeks), the animals were divided into three groups (6 females and 6 males per group): control, low-dose group (food supplemented with 300 mg/kg of the herbal product), and high-dose group (600 mg/kg).ResultsThe herbal product at a single dose of 2000 mg/kg did not induce mortality for 14 days. In the sub-acute study, administration of the product for 28 days at 1200 mg/kg/day had no effect on survival, appetite (water and food consumption), body weight, serum biochemical parameters (BUN, creatinine, AST, ALT, ALP, bilirubin, albumin), histology of vital organs (liver, kidney, heart, brain), and hematological markers related to erythrocyte, platelet, and leukocyte. Similarly, in the subchronic study, the product did not induce mortality, change in histology of the vital organs, or alteration in hematological or biochemical parameters (except for an increase in ALP in female rats received 600 mg/kg).ConclusionThe formulated product shows no signs of toxicity in rats up to 2000 mg/kg, 1200 mg/kg, and 600 mg/kg in acute, subacute, and subchronic phases, respectively. It is suggested to monitor ALP levels in females in case of long-term use of the product.
| S-EPMC10692756 | biostudies-literature
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.
| S-EPMC6976914 | biostudies-literature
Project description:Green tea is generally considered safe, but there have been concerns regarding side effects relating to the main component, catechins, especially hepatotoxicities. We have previously shown beneficial effects of fermented green tea with Aquilariae Lignum (fGT) via an oral route in diabetic and obese models. Thus, the toxicological safety of fGT was assessed at limited oral doses for a rodent. Mice or rats of both genders were orally administered distilled water as a control and fGT at 2.0, 1.0, and 0.5 g/kg. There were no mortalities or gross abnormalities in the fGT groups for 2 weeks following the single oral dose in mice. No fGT-relevant abnormalities were found in postmortem and histopathological examinations, suggesting LD50 of fGT at more than 2.0 g/kg with no specific target organs. There were also no fGT-relevant mortalities or abnormal signs in the repeated oral dose for 13 weeks in rats. In the fGT groups, no body weight changes or daily metabolic changes were found, and hematological and serum biochemical ranges were normal. The postmortem and histopathological examinations revealed few fGT-related abnormalities in most of the organs including the liver, although slight lymphoid cell hyperplasia in the lymph node was observed in a few rats with fGT at 2.0 g/kg. This may be secondary to increased immune response to the highest dose because there were no histopathological lesions or organ weight changes. It suggests nontoxic safety of fGT at up to 2.0 g/kg, which provides useful information for clinical use.
| S-EPMC6754909 | biostudies-literature
Project description:A polyherbal drug composed of leaves of Murraya koenigii L. Spreng, cloves of Allium sativum L., fruits of Garcinia quaesita Pierre, and seeds of Piper nigrum L. is a popular drug which has been used by indigenous practitioners in Sri Lanka for the treatment of diabetes mellitus and dyslipidemia. The acute toxicity assessment was conducted, following a single oral dose of 0.25-2.0?g/kg in healthy rats, and rats were observed up to 14 days. The hot water extract (1.0?g/kg) and the water?:?acetone extract (0.5, 1.0, and 1.5?g/kg) were administered to Wistar rats for 28 days in the subchronic study. Hypoglycemic and antihyperglycemic activities (dose response studies) of cold water, hot water, and water?:?acetone extracts of the polyherbal mixture were evaluated at the doses of 0.5, 1.0, and 1.5?g/kg in healthy and streptozotocin-induced diabetic rats (70?mg/kg, ip), respectively. Acute toxicity study showed that the polyherbal drug did not cause any change in animals throughout the experimental period of 14 days. The administration of the hot water extract and the water?:?acetone extract of the polyherbal drug for 28 days did not produce changes in the selected biochemical and hematological parameters in Wistar rats (p?>?0.05). The histological assessment corroborated the biochemical findings with no significant treatment-related changes in the kidney and liver. The treatment of polyherbal drug significantly lowered the serum glucose concentration compared to the diabetic control rats (p?<?0.05) while it did not lead to a severe reduction of glucose concentration in healthy rats. The hot water and water?:?acetone extracts of the polyherbal drug showed a statistically significant improvement on total area under the glucose tolerance curve in diabetic rats (p?<?0.05), reflecting dose-dependent antihyperglycemic effects of the drug. Based on the results, we conclude that the aforementioned antidiabetic polyherbal remedy is free of toxic/adverse effects at the equivalent human therapeutic dose in healthy Wistar rats and would be a safe therapeutic agent for long-term treatments.
| S-EPMC7388592 | biostudies-literature
Project description:In acute aristolochic acid nephropathy (AAN), aristolochic acid (AA) induces renal injury and tubulointerstitial fibrosis. However, the roles of microRNAs (miRNAs/miRs) and mRNAs involved in AAN are not clearly understood. The aim of the present study was to examine AA‑induced genome‑wide differentially expressed (DE) miRNAs and DE mRNAs using deep sequencing in mouse kidneys, and to analyze their regulatory networks. In the present self‑controlled study, mice were treated with 5 mg/kg/day AA for 5 days, following unilateral nephrectomy. AA‑induced renal injury and tubulointerstitial fibrosis were detected using hematoxylin and eosin staining and Masson's trichrome staining in the mouse kidneys. A total of 82 DE miRNAs and 4,605 DE mRNAs were identified between the AA‑treated group and the self‑control group. Of these DE miRNAs and mRNAs, some were validated using reverse transcription‑quantitative PCR. Expression levels of the profibrotic miR‑21, miR‑433 and miR‑132 families were significantly increased, whereas expression levels of the anti‑fibrotic miR‑122‑5p and let‑7a‑1‑3p were significantly decreased. Functions and signaling pathways associated with the DE miRNAs and mRNAs were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 767 DE pairs (in opposing directions) of miRNAs and their mRNA targets were identified. Among these, regulatory networks of miRNAs and mRNAs were analyzed using KEGG to identify enriched signaling pathways and extracellular matrix‑associated pathways. In conclusion, the present study identified genome‑wide DE miRNAs and mRNAs in the kidneys of AA‑treated mice, as well as their regulatory pairs and signaling networks. The present results may improve the understanding of the role of DE miRNAs and their mRNA targets in the pathophysiology of acute AAN.
| S-EPMC7453650 | biostudies-literature