Project description:Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before the acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin and hepatic cell necrosis. Moreover, LcS alleviated the acetaminophen-induced intestinal mucosal permeability, elevation in serum IL-1α and lipopolysaccharide, and decreased levels of serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol and sugars in the gut. Additionally, the transcriptome and proteomics showed that LcS mitigated the downregulation of metabolism and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
Project description:Differential gene expression in mice liver after carbon tetrachloride and acetaminophen administration. Livers from control mice were compared with drug treated mice livers at different time points. Keywords: Time-course
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver. To induce chronic liver fibrosis, seven-week-old mice received 0.6 ml/kg body weight of carbon-tetrachloride (CCl4) dissolved in corn-oil by intraperitoneal (i.p.) injection, twice a week for 10 weeks (n=3). As a control, same number of mice was injected with equal volume of corn-oil for 10 weeks.
Project description:Purpose : Identification of novel microRNA biomarkers in urine and plasma from rats with kidney or liver damage micoRNA-SEQ was used to analyze changes in miRNA profiles of tissue, plasma and urine samples of rats treated with either a nephrotoxicant (cisplatin) or one of two hepatotoxicants (Acetaminophen [APAP] or Carbon Tetrachloride [CCL4]).
Project description:Differential gene expression in mice liver after carbon tetrachloride and acetaminophen administration. Livers from control mice were compared with drug treated mice livers at different time points. Keywords: Time-course Mice (Mus musculus) belonging to control and carbon tetrachloride and acetaminophen-administered groups (n=4) were sacrificed. The livers were snap frozen in liquid nitrogen, and subsequently stored at -80ºC till further use. Liver samples were homogenized and total RNA was extracted with TRI reagent. 25 ug of total RNA was converted into labeled cDNA using CyScribe first strand cDNA labeling kit. The Cy5 and Cy3 labeled cDNAs were resuspended in Cyscribe Hyb buffer containing 10ug/ml sheared Salmon sperm DNA and 10ug/ml Yeast tRNA. The labeled samples were hybridized to the arrays and incubated for 16-18hrs at 42ºC. Fluorescent array images were collected for both Cy3 and Cy5 with molecular dynamics III scanner supported with ImageQuant v5.0. Image intensity data were extracted and analyzed with ArrayVision v8.0 analysis software. Background corrected data was LOWESS normalized and log ratios were calculated using Avadis v4. Further, mean log ratios were calculated for duplicate spots. Replicate experiments were carried out in dye swap manner for each time point.
Project description:Preclinical biomarkers useful for identification of idiosyncratic drugs have not been identified. It is hypothesized that patterns of transcript expression for the hepatotoxicants, including classical and idiosyncratic hepatotoxicants, are similar and the patterns differ from those of non-hepatotoxicants. This experiment is part of the biomarkers study, and focus on two clasical hepatotoxicants: Acetaminophen and Carbon tetrachloride. We have employed whole genome microarray expression profiling to identify liver gene expression changes induced by hepatotoxicants. For the same animal, urinary microRNA profiling were analyzed. APAP and CCl4 both significantly increased the urinary levels of 44 and 28 miRNAs, respectively. In addition, 10 of the increased miRNAs were in common between APAP and CCl4. Computational analysis was used to predict target genes of the 10 shared hepatotoxicant-induced miRNAs. From the same animals, liver gene expression profiling was performed using whole genome microarrays. Eight putative target genes were found to be significantly altered in the liver of APAP and CCl4 treated animals. Acetaminophen induced liver gene expression changes in rats (Six to seven week-old male Sprague-Dawley rats, provided by the US Food and Drug Administration National Center for Toxicological Research (NCTR) breeding colonies, were used for the study.) were measured at 6 hours, 24 hours, 3 days and 7 days after exposure to doses of 0, 100 and 1250 mg/kg. Carbon tetrachloride induced liver gene expression changes in rats were measured at 6 hours, 24 hours and 3 days after exposure to doses of 0, 50 and 2000 mg/kg. Each group has at least 4 animals, total of 96 samples.