BIOMAT Database Logo BIOMAT Database Logo

Reduction of fatty liver in rats by nicotinamide via the regeneration of the methionine cycle and the inhibition of aldehyde oxidase. 2021

Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Department of Drug Metabolism and Pharmacokinetics, Nonclinical Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd.

Nonalcoholic fatty liver disease, which has been rapidly increasing in the world in recent years, is roughly classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis. This study was based on our previous reports that stated that the combination treatment of N1-methylnicotinamide (MNA) and hydralazine (HYD) improves fatty liver in NAFL model rats. This finding was attributed to the MNA metabolism inhibition by HYD, which is a strong inhibitor of aldehyde oxidase (AO); this results in an increase in hepatic MNA and improved fatty liver. We hypothesized that orally administered nicotinamide (NAM), which is the precursor of MNA and is a form of niacin, would be efficiently metabolized by nicotinamide N-methyltransferase in the presence of exogenous S-adenosylmethionine (SAM) in NAFL rats. To address this issue, NAFL model rats were orally administered with NAM, SAM, and/or HYD. As a result, liver triglyceride (TG) and lipid droplet levels were barely altered by the administration of NAM, SAM, NAM+SAM, or NAM+HYD. By contrast, the triple combination of NAM+SAM+HYD significantly reduced hepatic TG and lipid droplet levels and significantly increased hepatic MNA levels. These findings indicated that the combination of exogenous SAM with AO inhibitors, such as HYD, has beneficial effects for improving fatty liver with NAM.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008715 Methionine A sulfur-containing essential L-amino acid that is important in many body functions. L-Methionine,Liquimeth,Methionine, L-Isomer,Pedameth,L-Isomer Methionine,Methionine, L Isomer
D009536 Niacinamide An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. Nicotinamide,Vitamin B 3,Vitamin PP,3-Pyridinecarboxamide,Enduramide,Nicobion,Nicotinsäureamid Jenapharm,Papulex,Vitamin B3,3 Pyridinecarboxamide,B 3, Vitamin,B3, Vitamin,Jenapharm, Nicotinsäureamid
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006830 Hydralazine A direct-acting vasodilator that is used as an antihypertensive agent. Hydrallazin,Apresoline,Apressin,Apressoline,Hydralazine Hydrochloride,Hydralazine mono-Hydrochloride,Hydrazinophthalazine,Nepresol,Hydralazine mono Hydrochloride,Hydrochloride, Hydralazine,mono-Hydrochloride, Hydralazine
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

Related Publications

Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Involvement of liver aldehyde oxidase in the reduction of nicotinamide N-oxide.
April 1984, Biochemical and biophysical research communications,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Reduction of cytochrome oxidase by liver aldehyde oxidase.
February 1955, The Journal of biological chemistry,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Chromate reduction by rabbit liver aldehyde oxidase.
May 1986, Biochemical and biophysical research communications,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Human liver aldehyde oxidase: inhibition by 239 drugs.
January 2004, Journal of clinical pharmacology,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Kinetic and inhibition studies on reduction of diphenyl sulfoxide by guinea pig liver aldehyde oxidase.
August 1986, Archives of biochemistry and biophysics,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Potent inhibition of human liver aldehyde oxidase by raloxifene.
January 2004, Drug metabolism and disposition: the biological fate of chemicals,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Involvement of liver aldehyde oxidase in sulfoxide reduction.
December 1982, Chemical & pharmaceutical bulletin,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Alleviation of fatty liver in a rat model by enhancing N1-methylnicotinamide bioavailability through aldehyde oxidase inhibition.
December 2018, Biochemical and biophysical research communications,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Thiamethoxam induces nonalcoholic fatty liver disease in mice via methionine metabolism disturb via nicotinamide N-methyltransferase overexpression.
June 2021, Chemosphere,
Chie Yokouchi, and Yukari Nishimura, and Hirohiko Goto, and Makoto Sato, and Yuya Hidoh, and Kenji Takeuchi, and Yuji Ishii
Metabolism of isovanillin by aldehyde oxidase, xanthine oxidase, aldehyde dehydrogenase and liver slices.
March 2005, Pharmacology,
Copied contents to your clipboard!