lithium-chloride and Chemical-and-Drug-Induced-Liver-Injury

The aging process is concerned with oxidative stress and causing malfunction of various organs such as the liver, kidney and heart. Lithium (Li) salts have shown anti-manic, anti-suicidal, and antioxidant properties. The current study is aimed to evaluate the possible inhibitory effects of various doses (10, 20 & 40mg/ml/kg) of Lithium chloride (LiCl) on D-galactose (D-gal)-produced aging model and explore the underlying mechanism. In the study 40 male rats were randomly alienated into 8 groups i.e. saline, LiCl (10, 20 & 40mg/ml/kg), D-gal and D-gal+LiCl (10, 20 & 40 mg/ml/kg). D-gal was given at a dosage of 300mg/ml/kg$ and animals received their respective treatment for 6 weeks [intraperitoneally (I.P), once daily]. After 2 weeks animals were decapitated and organs (liver, kidney, and heart) were removed for antioxidant assays. Blood was also collected for biochemical parameters. LiCl substantially decreased oxidative strain marker and increased enzymatic antioxidants in the liver, kidney, and heart of D-gal treated rats. LiCl also decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), creatine, urea, CK-MB, triglyceride, cholesterol, low-density lipoprotein (LDL) and increased high-density lipoprotein (HDL) in D-gal treated animals. High dose (80mg/ml/kg) of LiCl observed as the most effective dose against D-gal induced alterations. These finding LiCl inhibits D-gal induced liver, kidney and heart damages via its antioxidant potential.

Topics: Aging; Alanine Transaminase; Animal Structures; Animals; Antioxidants; Aspartate Aminotransferases; Biomarkers; Chemical and Drug Induced Liver Injury; Galactose; Heart; Kidney; Lithium Chloride; Liver; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase

Many studies of embryonic stem cells have investigated direct cell replacement of damaged tissues, but little is known about how donor cell-derived signals affect host tissue regeneration. We investigated the direct and indirect roles of human embryonic stem cell-derived cells in liver repair in mice.. To promote the initial differentiation of human embryonic stem cells into mesendoderm, we activated the β-catenin signaling pathway with lithium; cells were then further differentiated into hepatocyte-like cells. The differentiated cells were purified by indocyanine green staining and laser microdissection and characterized by immunostaining, polymerase chain reaction, biochemical function, electron microscopy, and transplantation analyses. To investigate indirect effects of these cells, secreted proteins (secretomes) were analyzed by a label-free quantitative mass spectrometry. Carbon tetrachloride was used to induce acute liver injury in mice; cells or secreted proteins were administered by intrasplenic or intraperitoneal injection, respectively.. The differentiated hepatocyte-like cells had multiple features of normal hepatocytes, engrafted efficiently into mice, and continued to have hepatic features; they promoted proliferation of host hepatocytes and revascularization of injured host liver tissues. Proteomic analysis identified proteins secreted from these cells that might promote host tissue repair. Injection of the secreted proteins into injured livers of mice promoted significant amounts of tissue regeneration without cell grafts.. Hepatocyte-like cells derived from human embryonic stem cells contribute to recovery of injured liver tissues in mice, not only by cell replacement but also by delivering trophic factors that support endogenous liver regeneration.

Topics: Animals; Biomarkers; Carbon Tetrachloride; Cell Differentiation; Cell Proliferation; Cell Separation; Cells, Cultured; Chemical and Drug Induced Liver Injury; Coculture Techniques; Disease Models, Animal; Embryonic Stem Cells; Hepatocytes; Humans; Immunohistochemistry; Induced Pluripotent Stem Cells; Laser Capture Microdissection; Lithium Chloride; Liver; Liver Regeneration; Mass Spectrometry; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Neovascularization, Physiologic; Polymerase Chain Reaction; Proteomics; Time Factors; Wound Healing

The present experiment used a saccharin aversion paradigm to evaluate the potential aversive action of T-2 toxin, a trichothecene mycotoxin that induces emesis and weight loss. Adult male rats were fed either a control diet or a diet adulterated with 640 ppm lithium chloride (positive control) or with 2.5, 5.0 or 10.0 ppm T-2 toxin and given access to a 0.1% saccharin solution and to tap water during four training days. The rats were then shifted to the control diet during three extinction days. Moderate saccharin aversion induced by the positive control diet and the 5.0 and 10.0 ppm T-2 diets was apparent on the third day of exposure and the aversion to the saccharin solution abated during the extinction trials. Saccharin aversion was evident at levels of T-2 toxin that did not induce obvious tissue pathology.

Topics: Animals; Chemical and Drug Induced Liver Injury; Chlorides; Dose-Response Relationship, Drug; Feeding Behavior; Food Preferences; Lithium; Lithium Chloride; Male; Rats; Rats, Inbred Strains; Saccharin; Sesquiterpenes; T-2 Toxin

The effect of short-term injection of chlorpromazine alone or combined with either LiCl or CsCl (1 mEq/kg/day) in organ toxicity was studied in the albino male mouse. Chlorpromazine was administered by gradual dose build-up regimens from 5 mg/kg to 50 mg/kg which was attained over a 40-day period followed by abrupt drug withdrawal for a subsequent 25-day observation period. Histological evaluation of 10 tissues selected indicates that the liver was the target organ. The Li-treatment resulted in variable liver lobular size with loss of cell definition and the kidney showed focal lymphatic aggregates related to vascular channel. Chlorpromazine-treated mice displayed variation in liver nuclei size and in cell structure definition. Combined injection of LiCl with the phenothiazine drug resulted in alteration in size of liver nuclei with a slight midlobular distribution. Minimal changes in lobular liver cells were noted subsequent to the Cs-treatment. This is compared to some dilation of liver central veins and few variations in hepatocyte size after combined injection of CsCl with chlorpromazine. There was a reduction in body weight of animals treated with the LiCl and chlorpromazine combination compared to that of mice receiving the chlorpromazine alone or in combination with CsCl. A rebound in body weight loss occurred during drug withdrawal in mice pretreated with chlorpromazine alone or combined with CsCl but not in mice coadministered LiCl with chlorpromazine. Mortality score indicates a profound lethal effect during administration of LiCl with the high dosage of the chlorpromazine used which was persistent during drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cesium; Chemical and Drug Induced Liver Injury; Chlorides; Chlorpromazine; Drug Synergism; Lithium; Lithium Chloride; Liver; Male; Mice; Rats; Rats, Inbred Strains