Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats

Autor: Hussam A. S. Murad, Z.J. Gazzaz, Ibraheem, Soad Shaker Ali
Rok vydání: 2017
Předmět:
Liver Cirrhosis
Male
0301 basic medicine
Physiology
Motor Disorders
Tetrazoles
Thioacetamide
Pharmacology
Biochemistry
Rats
Sprague-Dawley
Random Allocation
chemistry.chemical_compound
0302 clinical medicine
Malondialdehyde
Medicine
General Pharmacology
Toxicology and Pharmaceutics
Gamma-glutamyltransferase
lcsh:QH301-705.5
Hepatic encephalopathy
Research Articles
lcsh:R5-920
biology
Reverse Transcriptase Polymerase Chain Reaction
Candesartan
General Neuroscience
Alanine Transaminase
gamma-Glutamyltransferase
General Medicine
Glutathione
Treatment Outcome
Losartan
Liver
lcsh:Medicine (General)
Locomotion
medicine.drug
Immunology
Biophysics
Enzyme-Linked Immunosorbent Assay
Ocean Engineering
End Stage Liver Disease
03 medical and health sciences
Ammonia
Animals
Tumor Necrosis Factor-alpha
business.industry
Biphenyl Compounds
Motor dysfunction
Liver failure
Reproducibility of Results
Cell Biology
medicine.disease
Disease Models
Animal
030104 developmental biology
lcsh:Biology (General)
Alanine transaminase
chemistry
biology.protein
Benzimidazoles
business
Hepatic fibrosis
Angiotensin II Type 1 Receptor Blockers
030217 neurology & neurosurgery
Zdroj: Brazilian Journal of Medical and Biological Research, Volume: 50, Issue: 11, Article number: e6665, Published: 21 SEP 2017
Brazilian Journal of Medical and Biological Research v.50 n.11 2017
Brazilian Journal of Medical and Biological Research
Associação Brasileira de Divulgação Científica (ABDC)
instacron:ABDC
Brazilian Journal of Medical and Biological Research, Vol 50, Iss 11 (2017)
ISSN: 1414-431X
0100-879X
Popis: Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg−1·day−1) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg−1·day−1) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower “off-rate” from angiotensin-II receptors. Clinical trials are recommended.
Databáze: OpenAIRE
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