염소 산

Bile Acids -> Quant Bile Acids

Other Classes -> Organic Acids

log Kow = 2.02

2.02

2.02

Plates from dilute acetic acid

Crystals

In water, 175 mg/L at 20 °C

In water, 0.28 g/L at 15 °C

In alcohol 30.56 g/L; ether 1.22 g/L; chloroform 5.08 g/L; benzene 0.36 g/L; acetone 28.24 g/L; glacial acetic acid 152.12 g/L (all at 15 °C). Soluble in solutions of alkali hydroxides or carbonates

Soluble in ethanol, acetone, alkalies; very soluble in ethyl ether, chloroform

Soluble in glacial acetic acid; practically insoluble in benzene

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

This chemical does not meet GHS hazard criteria for 26.7% (4 of 15) of reports.

Warning

H312 (40%): Harmful in contact with skin [Warning Acute toxicity, dermal]

P261, P264, P264+P265, P272, P280, P302+P352, P305+P351+P338, P317, P321, P332+P317, P333+P317, P337+P317, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 15 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Cholan-24-oic acid, 3,7,12-trihydroxy-, (3.alpha.,5.beta.,7.alpha.,12.alpha.)-

Status: Active Update: 29-07-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/13911

Cholic acid: Does not have an individual approval but may be used under an appropriate group standard

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including cholic acid, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: No special environmental precautions required. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

Skin protection: Handle with gloves.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Aluminum-based antacids have been shown to adsorb bile acids in vitro and can reduce the bioavailability of Cholbam. Take Cholbam at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after an aluminum-based antacid.

Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the efficacy of Cholbam. Take Cholbam at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid binding resin.

Phenobarbital treatment increases the transport capacity (Vmax) for bile salt in the ileum of the rat. ... Rats treated with phenobarbital for 10 days had a 4-fold smaller cholic acid pool compared to control rats. Additionally, the daily production of cholic acid was decreased in phenobarbital treated rats compared to control rats. Phenobarbital has an antagonistic effect to the desired action of cholic acid in patients and may potentially endanger the established metabolic control. Therefore use of Phenobarbital in patients treated with cholic acid has been contraindicated.

Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine /with Cholbam/. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitoring of serum transaminases and bilirubin is recommended.

For more Interactions (Complete) data for CHOLIC ACID (8 total), please visit the HSDB record page.

In small, open label trials, cholic acid was found to improve fat soluble vitamin absorption and to ameliorate many of the clinical features of the bile acid synthetic defects including improvement in serum aminotransferase levels, decrease in bilirubin and jaundice and improvement in general health and growth. In some instances, higher doses of cholic acid were associated with elevations in serum aminotransferase levels. These abnormalities, however, were mild, transient and rapidly reversed with lowering the daily dose. There have been no reports of clinically apparent liver injury with jaundice attributed to cholic acid therapy given in standard doses.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2600(SRC), determined from a structure estimation method(2), indicates that cholic acid is expected to have slight mobility in soil(SRC). However, the pKa of cholic acid is 4.98(3), indicating that this compound will exist largely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Cholic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.7X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2015).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2600(SRC), determined from a structure estimation method(2), indicates that cholic acid is expected to adsorb to suspended solids and sediment(SRC). A pKa of 4.98(3) indicates cholic acid will exist largely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of 2.02(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2015).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cholic acid, which has an estimated vapor pressure of 5.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cholic acid may be removed from the air by wet and dry deposition(SRC). Cholic acid does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Cholic acid is used in biochemical research, as a pharmaceutical intermediate, and as an emulsifying agent in foods (up to 0.1%). It is also a medication used for the treatment of bile acid synthesis disorders due to single enzyme defects and for the adjunctive treatment of peroxisomal disorders including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption. HUMAN EXPOSURE AND TOXICITY: Cholic acid is a primary bile acid. Primary bile acids are biosynthesized in the liver and are key constituents of normal bile. When formulated and used as a treatment for patients with bile acid synthesis disorders the major toxic effect is on liver function. The dose of cholic acid to be administered to the patients is intended to restore a concentration that is equivalent to that physiologically present in humans. Therefore any perceived genotoxic risk from cholic acid and deoxycholic acid to the patients would be equivalent to that of a normal healthy adult that produces these bile acids intrinsically. Overall, cholic acid showed nonsignificant mutagenic activity in a battery of genotoxicity tests performed in vitro. ANIMAL STUDIES: Bile acids are known to regulate bile acid synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). Mice lacking the farnesoid X receptor (FXR) involved in the maintenance of hepatic bile acid levels are highly sensitive to cholic acid-induced liver toxicity. Serum aspartate aminotransferase (AST) activity was elevated 15.7-fold after feeding a 0.25% cholic acid diet for five days, whereas only slight increases in serum AST (1.7- and 2.5-fold) were observed in wild-type mice fed 0.25 and 1% cholic acid diet, respectively. Primary bile acids were studied as possible colon tumor promoters or inhibitors in a rat model of chemically induced colon cancer. Cholic acid feeding increased the number of animals with tumors, the number of tumors per animal, and the number of tumors per tumor-bearing animal. Tumor enhancement was attributed to deoxycholic acid, the bacterial metabolite of cholic acid. Administration of cholic acid (1.0% of the diet) to male rats for 3 days resulted in increased numbers of DNA synthesizing epithelial cells per colonic crypt column as compared to those found in either control or 0.2% cholic acid-fed rats. The mutagenicity of bile acids was detected by a fluctuation test using Salmonella typhimurium TA100 and TA98 as tester strains. Cholic acid and deoxycholic acid were mutagenic in this test. The mutagenicity of the bile acids on a molar basis was roughly one-fourth that of methyl methanesulfonate, a moderately potent mutagen. 0.5% cholic acid ingested by pregnant hamsters, caused ductal/ductular proliferation and hepatobiliary inflammatory damage in a different degree of intensity in adult animals and mild intensity in the young; and also the number of the young was reduced in the litter. The ingestion of these bile acids by hamsters, during gestational period caused different degrees of toxicity on maternal and neonatal hepatobiliary systems. In rat developmental studies there was apparent pathological change of fetal rats brain in cholic acid-treated groups, the neuronal degeneration and the mitochondria swelling was mainly found in low cholic acid group, the neuronal necrosis and the mitochondria decrease was mainly found in high cholic acid group.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of cholic acid can be estimated to be 2600(SRC). According to a classification scheme(2), this estimated Koc value suggests that cholic acid is expected to have slight mobility in soil. However, soil mobility may be slightly higher given a measured log Kow of 2.02(3). The pKa of cholic acid is 4.98(4), indicating that this compound will exist largely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

/HUMAN EXPOSURE STUDIES/ Qualitative and quantitative changes in intralumenal bile acid composition may alter cholesterol absorption and synthesis and low-density lipoprotein (LDL) receptor expression. The role of cholic acid (CA) in cholesterol absorption in humans remains unclear and, thus, was examined in the current study. In a crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day (CA) or no bile acid supplement (control) while being fed a controlled diet (American Heart Association (AHA) heart-healthy diet). A liquid meal of defined composition was given on day 14 of the diet, and lumenal samples were collected. Thereafter, cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods from days 16 to 20. With CA treatment, bile was enriched significantly with CA (P < 0.0004) to 60.2% +/- 2.4% (mean +/- SEM) compared with 43.3% +/- 2.4% for controls. CA plus diet treatment significantly increased (P = 0.013) cholesterol absorption (72.6% +/- 2.9%) compared with diet treatment alone (60.4% +/- 2.9%). Percentage micellar cholesterol was increased by CA plus diet treatment vs. diet alone after meal ingestion (P = 0.004). Plasma total and high-density lipoprotein (HDL) and LDL cholesterol was unchanged with CA treatment. Thus, enrichment in lumenal bile with CA results in an increase in cholesterol absorption, an effect potentially mediated by enhanced cholesterol solubilization in micelles.

/HUMAN EXPOSURE STUDIES/ Clinical data has shown there to be four successful pregnancies in patients who had been receiving Orphacol, all producing healthy babies.

/SIGNS AND SYMPTOMS/ Discontinue treatment with Cholbam at any time if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis. Concurrent elevations of serum gamma glutamyltransferase (GGT) and serum alanine aminotransferase (ALT) may indicate Cholbam overdose. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.

/BIOMONITORING/ Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas-liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P =.04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P <.05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD.

For more Human Toxicity Excerpts (Complete) data for CHOLIC ACID (7 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Cholic acid

Ambiguous-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

An estimated BCF of 3 was calculated in fish for cholic acid(SRC), using a log Kow of 2.02(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including cholic acid, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

Cholic acid is a primary bile acid. Primary bile acids are biosynthesised in the liver and are key constituents of normal bile. The two primary bile acids synthesised by the liver, cholic acid and chenodeoxycholic acid, serve several important physiological functions. Cholic acid is the predominant primary bile acid in bile. It represents between approximately half and two thirds of the primary bile acids produced in adult. In addition to facilitating fat absorption from the gastrointestinal tract and to participating in the regulation of cholesterol homeostasis, the primary bile acids provide the major driving force for the promotion and secretion of bile. They are essential to the development of the enterohepatic circulation, which is necessary for the elimination of toxic endogenous or exogenous substances.

Cholic acid is synthesized in the liver from cholesterol. It undergoes enterohepatic circulation, in which its principal functions include induction of bile flow; feedback inhibition of bile acid synthesis; modulation of cholesterol synthesis; elimination of cholesterol; and the facilitation of dispersion and absorption of lipids and fat-soluble vitamins through the formation of micelles.

Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and pharmacological concentrations of BAs.

Cholic acid is a primary bile acid synthesized from cholesterol in the liver. In bile acid synthesis disorders due to single enzyme defects (SEDs) in the biosynthetic pathway, and in peroxisomal disorders (PDs) including Zellweger spectrum disorders, deficiency of primary bile acids leads to unregulated accumulation of intermediate bile acids and cholestasis. Bile acids facilitate fat digestion and absorption by forming mixed micelles, and facilitate absorption of fat-soluble vitamins in the intestine. Endogenous bile acids including cholic acid enhance bile flow and provide the physiologic feedback inhibition of bile acid synthesis. The mechanism of action of cholic acid has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR). FXR regulates enzymes and transporters that are involved in bile acid synthesis and in the enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions.

The mechanism and sequence of side chain hydroxylation of cholesterol in bile acid synthesis was studied in the isolated perfused rabbit liver. A comparison was made between the importance of 26- and 25-hydroxylation in cholic acid biosynthesis in the rabbit. The formation of [G-(3)H]cholic acid was observed when the liver was perfused with 5beta-[G-(3)H]cholestane-3alpha, 7alpha-diol, 5beta-[G-(3)H]cholestane-3alpha, 7alpha-12alpha-triol, and 5beta-[G-(3)H]cholestane-3alpha, 7alpha, 26-triol. No [G-(3)H]chenodeoxycholic acid was detected in the bile. These findings indicate that potential precursors of chenodeoxycholic acid were hydroxylated at position 12alpha either subsequent to or before hydroxylation of the cholesterol side chain. In addition, no other intermediates (tetrahydroxy or pentahydroxy bile alcohols) were found in the bile when these compounds were perfused in the liver. Bile acid precursors were detected in bile when the rabbit liver was perfused with 5beta-[24-(14)C]cholestane-3alpha, 7alpha, 25-triol. The 5beta-[24-(14)C]cholestane-3alpha, 7alpha, 25-triol was hydroxylated in the liver at the 12alpha position to yield the corresponding 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol. The tetrol was further metabolized to a series of pentols (5beta-cholestane-3alpha, 7alpha, 12alpha, 22, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 24, 25-pentol; and 5beta-cholestane-3alpha, 7alpha, 12alpha, 25, 26-pentol). The major bile acid obtained from the perfusion of the 5beta-cholestane-3alpha, 7alpha, 25-triol was cholic acid. The experiments indicated that in the rabbit liver 12alpha-hydroxylation can occur after hydroxylation of the cholesterol side chain at either C-25 (5 beta-cholestane-3alpha, 7alpha, 25-triol) or C-26 (5beta-cholestane-3alpha, 7alpha-26-triol). Apparently, the rabbit can form cholic acid via the classical 26-hydroxylation pathway as well as via 25-hydroxylated intermediates.

In classic cholic acid biosynthesis, a series of ring modifications of cholesterol precede side chain cleavage and yield 5beta-cholestane-3alpha, 7alpha, 12alpha-triol. Side chain reactions of the triol then proceed either by the mitochondrial 27-hydroxylation pathway or by the microsomal 25-hydroxylation pathway. We have developed specific and precise assay methods to measure the activities of key enzymes in both pathways, 5beta-cholestane-3alpha, 7alpha, 12alpha-triol 25- and 27-hydroxylases and 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol 23R-, 24R-, 24S- and 27-hydroxylases. The extracts from either the mitochondrial or microsomal incubation mixtures were purified by means of a disposable silica cartridge column, derivatized into trimethylsilyl ethers, and quantified by gas chromatography;-mass spectrometry with selected-ion monitoring in a high resolution mode. Compared with the addition of substrates in acetone, those in 2-hydroxypropyl-beta-cyclodextrin increased mitochondrial triol 27-hydroxylase activity 132% but decreased activities of the enzymes in microsomal 25-hydroxylation pathway (triol 25-hydroxylase and 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol 23R-, 24R-, 24S- and 27-hydroxylases) 13;-60% in human liver. The enzyme activities in both pathways were generally 2- to 4-times higher in mouse and rabbit livers compared with human liver. In all species, microsomal triol 25-hydroxylase activities were 4- to 11-times larger than mitochondrial triol 27-hydroxylase activities but the activities of tetrol 24S-hydroxylase were similar to triol 27-hydroxylase activities in our assay conditions. The regulation of both pathways in rabbit liver was studied after bile acid synthesis was perturbed. Cholesterol feeding up-regulated enzyme activities involved in both 25- (64;-142%) and 27- (77%) hydroxylation pathways, while bile drainage up-regulated only the enzymes in the 25-hydroxylation pathway (178;-371%). Using these new assays, we demonstrated that the 25- and 27-hydroxylation pathways for cholic acid biosynthesis are more active in mouse and rabbit than human livers and are separately regulated in rabbit liver.

Deoxycholic acid is the main metabolite of cholic acid. Patients with 3alpha-HSD deficiency and delta4-3-oxoR deficiency and subjects with a normal bile acid metabolism have shown that upon treatment with cholic acid, serum and bile predominantly contain cholic acid and deoxycholic acid, while chenodeoxycholic acid and its metabolites appear to be reduced. Under cholic acid treatment, patients are therefore exposed to higher than normal deoxycholic acid concentrations, although the exact quantifications of these concentrations have not been described. In single- and repeat-dose studies, deoxycholic acid showed lethal effects, gastrointestinal and hepatic toxicities at approximately half the doses needed for cholic acid to produce the same effects. It is therefore considered that deoxycholic acid is more toxic than cholic acid and may in fact be the causative agent of some of cholic acid's toxicity. Mutagenicity data from bacterial test for deoxycholic acid is ambiguous but deoxycholic acid was genotoxic in an in vitro micronucleus assay. Additionally, ... the genotoxic potential of BA (focusing on chenodeoxycholic acid and deoxycholic acid) on human colonocytes and colon tumor cells HT 29 by a comet assay /was investigated/. In both cell types a clear dose-dependent genotoxic effect induced by the two bile acids was observed, with deoxycholic acid being more genotoxic. Viability of cells appeared to be greater than 75%. Use of a nuclease III modified comet assay suggested that the DNA damage could be mediated by reactive oxygen species production but was somewhat protected by inclusion of anti-oxidants. Short term carcinogenicity studies suggest that deoxycholic acid like cholic acid has carcinogenicity promoting properties. In rat liver, deoxycholic acid (75-150 mg/kg) exerted promoting activity as evidenced by significantly increased values of alpha-glutamyl transpeptidase-positive (alpha-GT+) liver foci compared with the corresponding controls given the carcinogen, diethylnitrosamine (DEN) alone. Deoxycholic acid (20 mg/kg) enhanced the development and growth of azoxymethane (AOM)-induced aberrant crypt foci in rat colons. In a parallel study, deoxycholic acid in the absence of AOM did not significantly induce aberrant crypt foci. However, /a study/ concluded that deoxycholic acid may act not only as promoters but also initiators of the multistage process of carcinogenesis.

Cholic acid has known human metabolites that include Cholic acid glucuronide.

G1JO7801AE

CHOLIC ACID

Established Pharmacologic Class [EPC] - Bile Acid

Chemical Structure [CS] - Bile Acids and Salts

Cholic acid is a Bile Acid.

CHOLIC ACID

Following ingestion, absorption of cholic acid will first be by the small intestine, and is then transported to the liver by the blood for further processing.

Orally administered cholic acid is subject to the same metabolic pathway as endogenous cholic acid. Cholic acid is absorbed by passive diffusion along the length of the gastrointestinal tract. Once absorbed, cholic acid enters into the body's bile acid pool and undergoes enterohepatic circulation mainly in conjugated forms. In the liver, cholic acid is conjugated with glycine or taurine by bile acid-CoA synthetase and bile acid-CoA: amino acid N-acetyltransferase. Conjugated cholic acid is actively secreted into bile mainly by the Bile Salt Efflux Pump (BSEP), and then released into the small intestine, along with other components of bile. Conjugated cholic acid is mostly re-absorbed in the ileum mainly by the apical-sodium-dependent-bile acid transporter, passed back to the liver by transporters including sodium-taurocholate cotransporting polypeptide and organic anion transport protein and enters another cycle of enterohepatic circulation. Any conjugated cholic acid not absorbed in the ileum passes into the colon where deconjugation and 7-dehydroxylation are mediated by bacteria to form cholic acid and deoxycholic acid which may be re-absorbed in the colon or excreted in the feces. The loss of cholic acid is compensated by de-novo synthesis of cholic acids from cholesterol to maintain the bile acid pool in healthy subjects.

Excretion studies in rat showed that cholic acid (CA) is almost exclusively excreted in the feces in the form of metabolite. Only minor amounts of CA were found in the unconjugated form in rat feces. Urinary excretion of bile acids is minimal and in mice fed a 1% CA diet, the excretion of bile acids was 2000-fold higher in feces than in urine

Cholic acid was shown to be mainly absorbed in the distal (ileal) rather than proximal segments of the small intestine in the guinea pig.

For more Absorption, Distribution and Excretion (Complete) data for CHOLIC ACID (9 total), please visit the HSDB record page.

Found conjugated with glycine or taurine in the bile of most vertebrates; Used as a gallbladder stimulant; [Merck Index] Used in biochemical research, as an intermediate for pharmaceuticals, and as a food emulsifying agent; [Hawley]

Biochemical research, pharmaceutical intermediate, emulsifying agent in foods (up to 0.1%)

AGENT IN BIOCHEMICAL RESEARCH; CHEM INT FOR PHARMACEUTICALS

EMULSIFYING AGENT FOR EGG WHITES

MEDICATION

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

ALKALINE EXTRACTION OF BOVINE BILE, NEUTRALIZATION WITH ACID, FORMATION OF THE MAGNESIUM SALT, FILTRATION, SEPARATION OF DEOXYCHOLIC ACID, AND ACIDIFICATION OF THE FILTRATE

Extraction from beef bile.

Derivation: From glycocholic and taurocholic acids in bile; organic synthesis.

Oral: 50 mg and 250 mg hard capsules, Orphacol (Active substance: Cholic acid)

Cholbam is available in two capsule strengths. 50 mg capsule: Size number 2 Swedish orange capsule with cap imprinted with "50 mg" and body imprinted with "ASK001". The capsules contain a white to off-white powder. 250 mg capsule: Size number 0 white capsule with a cap imprinted with "250 mg" and body imprinted with "ASK002". The capsules contain a white to off-white powder.

Food Additives -> EMULSIFIER -> JECFA Functional Classes

Cosmetics -> Solvent

Cholan-24-oic acid, 3,7,12-trihydroxy-, (3.alpha.,5.beta.,7.alpha.,12.alpha.)-: ACTIVE

MAJOR HUMAN BILE ACIDS ARE CHOLIC & DEOXYCHOLIC ACIDS & CHENODEOXYCHOLIC ACID... CHOLIC ACID & CHENODEOXYCHOLIC ACID ARE PRESENT IN BILE IN ABOUT EQUAL PROPORTIONS (30%-40%)...LESS DEOXYCHOLIC ACID (10%-20%). ...FORMED FROM CHOLESTEROL IN LIVER.

BILE ACIDS, PRESENT AS SODIUM SALTS OF A MIXTURE OF ACIDS, ARE DIVIDED INTO 2 GROUPS: 1) GLYCOCHOLIC ACIDS /CONJUGATES OF CHOLIC ACID WITH GLYCINE/ & 2) TAUROCHOLIC ACIDS. /CONJUGATES OF CHOLIC ACID WITH TOURINE/

The most abundant bile acid