Deoxycholic Acid

...COMPETITION FOR EXTRAVASCULAR BINDING SITES BY DEOXYCHOLIC ACID MAY EXPLAIN REDUCED VOL OF DISTRIBUTION OF BROMSULFOPHTHALEIN IN PRESENCE OF BILE ACID.

COMPD INCL DEOXYCHOLATE POTENTIATED ANTISTAPHYLOCOCCI ACTIVITY OF GENTAMYCIN, MONOMYCIN, KANAMYCIN, & NEOMYCIN.

Deoxycholic acid was tested alone and as a promoter of N-nitrosobis(2-hydroxypropyl)amine induced carcinogenesis in the hamster. Three groups of 5 to 6-wk-old male Syrian hamsters (SYR)/NI were used and 10 animals per group were given subcutaneous injections of 0.9% NaCl, once per week for 5 weeks. Group 1 received no further treatment; groups 2 and 3 received 0.1% and 0.5% DCA in their feed for 30 weeks, respectively. Animals were autopsied at week 35. There was no significant difference in body wt. between groups 1 and 2, whereas there was a significant decrease in body weight for group 3 (P<0.005). There were no liver tumors, bile duct proliferation, gallbladder lesions or polyps, pancreatic lesions, or pancreatic duct hyperplasia in these 3 groups. In the promoter study, three groups of 5 to 6-wk-old hamsters (number not stated) were given a subcutaneous injection of 500 mg/kg body wt. N-nitrosobis(2-hydroxypropyl)amine per week for 5 weeks. Group 4 received no further treatment and the N-nitrosobis(2-hydroxypropyl)amine treatment was followed by 0.1% DCA (group 5) , or 0.5% DCA (group 6) in the feed for 30 weeks. There was a significant body weight loss (P<0.005) for groups 5 and 6 compared to group 4. DCA significantly increased the induction of cholangiocarcinomas 10/19 in group 5 (P<0.006); 9/25 in group 6 (P<0.05) compared to group 4 which had 1/15. Pancreatic carcinomas were significantly increased in group 5 (14/19, P<0.03). Therefore, under the conditions of this experiment, DCA was not carcinogenic when given alone but was an effective promoter of N-nitrosobis(2-hydroxypropyl)amine-induced hepatic and pancreatic carcinogenesis in hamsters.

DEOXYCHOLIC /ACID IS/...FORMED IN INTESTINE BY ACTION OF /ENTERIC/ BACTERIA ON SECRETED BILE ACIDS.

OCCURS IN BILE OF MAN, OX, SHEEP, DOG, GOAT & RABBIT.

Excess bile acids reaching the colon can reduce net water absorption and cause diarrhea. /Bile acids/

FOLLOWING IV INJECTION OF BILE SALTS...THERE IS MARKED FALL IN BLOOD PRESSURE ACCOMPANIED BY A BRADYCARDIA. ...JAUNDICE... IV, BILE SALTS CAUSE SKELETAL MUSCULAR HYPERACTIVITY, TWITCHING, SPASM, DECR IN THRESHOLD FOR NERVE IMPULSES. ...BILE ACIDS...CAUSE LYSIS OF RED & WHITE BLOOD CELLS. /BILE SALTS & BILE ACIDS/

Drug Induced Liver Injury Rank (DILIrank 2.0)

Deoxycholic acid

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

IN DOGS, BILE SALTS DAMAGE GASTRIC MUCOSAL BARRIER, WHICH RESULTS IN BACK DIFFUSION OF ACID. ALTHOUGH NET DIFFUSION INTO LUMEN IS DIMINISHED, MUCOSAL CONCN IS INCREASED & ULCERATION OCCURS. /BILE SALTS/

DEOXYCHOLIC ACID ADDED TO CULTURES: WAS HIGHLY TOXIC TO RAT FIBROBLASTS & COLON CANCER CELLS, LESS TOXIC TO LIVER EPITHELIAL CELLS.

3 MMOL/L INSTILLED INTO RAT COLON LUMEN INCR PERMEABILITY TO WATER & TO UREA, MANNITOL & LACTOSE; DID NOT AFFECT OSMOTIC FILTRATION COEFFICIENTS.

CHOLIC ACID, TAUROCHOLIC ACID, GLYCOCHOLIC ACID, & DEOXYCHOLIC ACID EXERTED ANTIMICROBIAL ACTIVITY AGAINST STAPH IN VITRO: DEOXYCHOLATE MOST EFFECTIVE.

Although hepatocarcinogenesis has been reported to be promoted by exogenous administration of bile acids, the relation of endogenous bile acids to hepatocarcinogenesis is not completely understood. This study investigates the relationship between serum concentration of bile acids, the appearance of preneoplastic change, glutathione S-transferase placental form positive foci in the liver of male Donryu rats which had been fed 0.06% 3'-methyl-4-dimethylamino-azobenzene, and the effects of gomisin A, previously reported to inhibit the tumor promotion process. During the feeding of 3'-methyl-4-dimethylamino-azobenzene for 5 wks, the concn of serum bile acids were found to have increased significantly to several times the levels found at the start of the experiment. The increase of serum bile acids, especially deoxycholic acid, and the appearance of preneoplastic lesions, the number and area of glutathione S-transferase placental-positive foci in the liver, were significantly inhibited by simultaneous oral administration of gomisin A (30 mg/kg). When deoxycholic acid (100 mg/kg) was orally administered after an initiation by 3'-methyl-4-dimethylamino-azobenzene, serum bile acids and preneoplastic changes were significantly increased, these increases were inhibited by combined feeding of 0.03% gomisin A in the diet. There were good correlations between the serum concn of deoxycholic acid and the number of glutathione S-transferase placental-positive foci in the liver in both experimental protocols. These results confirm that deoxycholic acid is an endogenous risk factor for hepatocarcinogenesis and suggest that anti-promoter effect of gomisin A is based on improving metabolism of bile acids, including deoxycholic acid.