Lithocholic acid

Lithocholic acid is a toxic secondary bile acid, causes intrahepatic cholestasis, has tumor-promoting activity.Target: OthersLithocholic acid has been used in a study to assess cholestasis and its action on several organs and tissues in rats. It has also been used in a study to investigate the regulation of hepatic phospholipid and bile acid homeostasis through SMAD3 activation by TGFβ. It has been implicated in human and experimental animal carcinogenesis. Preliminary in vitro research suggests that LCA selectively kills neuroblastoma cells, while sparing normal neuronal cells and is cytotoxic to numerous other malignant cell types at physiologically relevant concentrations.

Signaling Pathways >> Autophagy >> Autophagy

Natural Products >> Acids and Aldehydes

Research Areas >> Metabolic Disease

Human Endogenous Metabolite

[1]. Jenkins, D.J., et al., Effect on blood lipids of very high intakes of fiber in diets low in saturated fat and cholesterol. N Engl J Med, 1993. 329(1): p. 21-6.

[2]. Goldberg, A.A., et al., Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells. Oncotarget, 2011. 2(10): p. 761-82.

[3]. Matsubara, T., et al., TGF-beta-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury. J Lipid Res, 2012. 53(12): p. 2698-707.

[4]. Yang R, et al. Metabolomic analysis of cholestatic liver damage in mice. Food Chem Toxicol. 2018 Jul 14;120:253-260.

3-Methyladenine | Hydrocortisone | Acetylcysteine(N-acetylcysteine) | Retinoic acid | Melatonine | Dinoprostone | Nicotinamide | Adenosine triphosphate | 4-Acetamidophenol | Prostaglandin E1 | Dehydroepiandrosterone | Corticosterone | Progesterone | Docosahexaenoic Acid | NAD+

DATA ITEMS CITED :

23

MOLECULAR FORMULA :

C24-H40-O3

MOLECULAR WEIGHT :

376.64

WISWESSER LINE NOTATION :

L E5 B666TJ A E FY&2VQ OQ -B&AEFMO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3900 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8800 mg/kg

SEX/DURATION :

female 0-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

16 gm/kg

SEX/DURATION :

female 0-19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

30160 ug/kg

SEX/DURATION :

female 12-19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

37700 ug/kg

SEX/DURATION :

female 12-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intrauterine

DOSE :

18850 ug/kg

SEX/DURATION :

female 5 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :

Mutation test systems - not otherwise specified

MUTATION DATA

TYPE OF TEST :

DNA adduct

TEST SYSTEM :

Mammal - species unspecified Lymphocyte

DOSE/DURATION :

10 mg/L

REFERENCE :

CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 15,1911,1994