vitamin-u and Chemical-and-Drug-Induced-Liver-Injury

The objective of this study was to examine the protective effects of S-methyl methionine sulfonium chloride (MMSC) against galactosamine (GalN)-induced brain and cerebellum injury in rats. A total of 22 female Sprague-Dawley rats were randomly divided into four groups as follows: Group I (n = 5), intact animals; Group II (n = 6), animals received 50 mg/kg/day of MMSC by gavage technique for 3 consecutive days; Group III (n = 5), animals injected with a single dose of 500 mg/kg of GalN intraperitoneally (ip); and Group IV (n = 6), animals injected with the same dose of GalN 1 h after MMSC treatment. After 6 h of the last GalN treatment (at the end of the experiments), all animals were killed under anesthesia, brain and cerebellum tissues were dissected out. Reduced glutathione, total antioxidant status levels, and antioxidant enzymes (catalase, superoxide dismutase, and glutathione-related enzymes), aryl esterase, and carbonic anhydrase activities remarkably declined whereas advanced oxidized protein products, reactive oxygen species, total oxidant status, oxidative stress index levels, and myeloperoxidase, acetylcholinesterase, lactate dehydrogenase, and xanthine oxidase activities were significantly elevated in the GalN group compared with intact rats. In contrast, the administration of MMSC to GalN groups reversed these alterations. In conclusion, we may suggest that MMSC has protective effects against GalN-induced brain and cerebellar toxicity in rats.

Topics: Acetylcholinesterase; Animals; Antioxidants; Brain; Carbonic Anhydrases; Catalase; Cerebellum; Chemical and Drug Induced Liver Injury; Chlorides; Female; Galactosamine; Glutathione; Lactate Dehydrogenases; Methionine; Oxidants; Oxidative Stress; Peroxidase; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sulfonium Compounds; Superoxide Dismutase; Vitamin U; Xanthine Oxidase

In this study, we aimed to investigate the effects of vitamin U (Vit U) on valproic acid (VPA)-induced liver damage. Female Sprague Dawley rats were randomly divided into four groups. Group I was intact control animals. Group II was control rats given Vit U (50 mg/kg/day) for fifteen days. Group III was given only VPA (500 mg/kg/day) for fifteen days. Group IV was given VPA+Vit U (in same dose and time). Vit U was given to rats by gavage and VPA was given intraperitoneally. On the 16th day of experiment, all the animals were fasted overnight and then sacrificed under ether anesthesia. Liver tissue was taken from animals, homogenized in 0.9% saline to make up to 10% homogenate. Liver aspartate and alanine transaminases, alkaline phosphatase, lactate dehydrogenase, myeloperoxidase, sorbitol dehydrogenase, glutamate dehydrogenase and xanthine oxidase activities and lipid peroxidation levels were increased and paraoxonase activity and glutathione levels were decreased in VPA group. Treatment with Vit U reversed these effects. These results demonstrated that administration of Vit U is a potentially beneficial agent to reduce the liver damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress.

Topics: Animals; Chemical and Drug Induced Liver Injury; Female; Liver; Random Allocation; Rats; Rats, Sprague-Dawley; Valproic Acid; Vitamin U

Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methionine and glutathione biosynthesis, Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer protection against acetaminophen-induced injury in vivo. Since SMM is only synthesized in plants, Bhmt2 exerts its beneficial effect in a diet-dependent manner. Identification of Bhmt2 and the affected biosynthetic pathway demonstrates how a novel method of integrative genomic analysis in mice can provide a unique and clinically applicable approach to a major public health problem.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Betaine-Homocysteine S-Methyltransferase; Chemical and Drug Induced Liver Injury; Diet; Gene Expression Profiling; Liver; Liver Failure, Acute; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred Strains; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Sequence Analysis, DNA; Vitamin U

Topics: Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Fructose-Bisphosphate Aldolase; Glucosephosphate Dehydrogenase; Hepatitis; L-Lactate Dehydrogenase; Malate Dehydrogenase; Methionine; Pharmacology; Rats; Research; Toxicology; Transaminases; Vitamin U