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Hepatotoxicity effect of short-term Bradykinin potentiating factor in cholestatic rats
- Source :
- Toxicology letters. 301
- Publication Year :
- 2018
-
Abstract
- Background Drug-induced hepatotoxicity is an extremely widespread condition and is responsible for a variety of pathological effects on the liver. It was reported that hepatotoxicity induced by angiotensin converting enzyme inhibitors (ACEIs) is cholestasis mediated hepatitis. Bradykinin-potentiating factor (BPF) is one of the natural ACEIs. Although prolonged treatment with ACEIs provides protection against liver injury, the effect of short-term treatment with ACEIs has not been fully elucidated before. Thereby, the present study sought to determine if transient ACE inhibition may exacerbate the hepatotoxicity caused by bile duct ligation (BDL) in rats. Methods Twenty one Wistar rats were divided into 3 groups: Sham-operated group, bile duct ligated (BDL) rats, and BDL rats treated for short-term with BPF (1 μg/kg body weight) day after day for one week and biochemical parameters were measured. Also, we assessed expression level of ACE1 and detection of hepatotoxicity in the liver tissues of different groups. Results There was a significant increase in liver enzymes, bilirubin levels, and oxidative stress in the BDL group after treatment with BPF as compared to BDL group. We found overexpression of ACE1 gene in BDL group compared to BPF and Sham-operated control group. Histopathological examination of liver treated with BPF showed severe degeneration hepatic architecture and hepatocytes as compared to BDL group. Collagen deposition increased after BPF treatment as compared to BDL groups. Conclusion The present investigation suggests and recommends that short- term ACE inhibition pathway potentiates liver fibrosis during cholestasis disease.
- Subjects :
- 0301 basic medicine
Male
Bradykinin
Pharmacology
Peptidyl-Dipeptidase A
Toxicology
medicine.disease_cause
digestive system
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cholestasis
Malondialdehyde
medicine
Animals
Aspartate Aminotransferases
Rats, Wistar
Pathological
Ligation
Glutathione Transferase
Hepatitis
Liver injury
biology
Dose-Response Relationship, Drug
business.industry
Bile duct
Angiotensin-converting enzyme
Alanine Transaminase
Bilirubin
General Medicine
medicine.disease
Glutathione
digestive system diseases
Rats
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
chemistry
Gene Expression Regulation
Liver
biology.protein
Hepatocytes
Bile Ducts
Chemical and Drug Induced Liver Injury
business
Oligopeptides
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- ISSN :
- 18793169
- Volume :
- 301
- Database :
- OpenAIRE
- Journal :
- Toxicology letters
- Accession number :
- edsair.doi.dedup.....3d9645d62bdbe810d56ffc7780188b00