The influence of ursodeoxycholic acid (UDCA) on griseofulvin (GF)-induced protoporphyria

Irifune, Hiroko; Nonaka, Shigeo; Tsukazaki, N; Ohgami, Taro; Yoshida, H

doi:10.1016/0923-1811(90)90189-k

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…UDCA leads to remarkable hepatic atrophy associated with many focal areas of necrosis and hepatotoxity in mice treated with griseofulvin, that was not evident in the mice treated with griseofluvin alone [ 153 ].…”

Section: Potentially Toxic Molecular Properties Of Udcamentioning

confidence: 99%

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Kotb

2012

IJMS

View full text Add to dashboard Cite

Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

show abstract

Section: Potentially Toxic Molecular Properties Of Udcamentioning

confidence: 99%

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Kotb

2012

IJMS

View full text Add to dashboard Cite

show abstract

“…In animal studies, published results are contradictory; in mice treated with Gris, it was reported that URSO administration may have a cytoprotective and choleretic action on the liver injury induced by Gris [ 33 , 34 ] although Irifune et al [ 35 ] did not notice any effect after administration of URSO in the same animal model.…”

Section: Discussionmentioning

confidence: 99%

Experimental Protoporphyria: Effect of Bile Acids on Liver Damage Induced by Griseofulvin

Martínez

Ruspini

Afonso

et al. 2015

BioMed Research International

View full text Add to dashboard Cite

The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris) was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA), dehydrocholic (DHA), chenodeoxycholic, or ursodeoxycholic (URSO). The administration of Gris alone increased the activities of glutathione reductase (GRed), superoxide dismutase (SOD), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), and glutathione-S-transferase (GST), as well as total porphyrins, glutathione (GSH), and cytochrome P450 (CYP) levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris.

show abstract

The influence of ursodeoxycholic acid (UDCA) on griseofulvin (GF)-induced protoporphyria

Cited by 2 publications

References 0 publications

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Experimental Protoporphyria: Effect of Bile Acids on Liver Damage Induced by Griseofulvin

Contact Info

Product

Resources

About