The anti-inflammatory and anti-fibrotic effects of tadalafil in thioacetamide-induced liver fibrosis in rats

• Published in: Canadian journal of physiology and pharmacology 2018-12, Vol.96 (12), p.1308-1317
• Main Authors: Mansour, Heba M, Salama, Abeer A.A, Abdel-Salam, Rania M, Ahmed, Naglaa A, Yassen, Noha N, Zaki, Hala F
• Format: Article
• Language: English
• Subjects: Actin; actine du muscle lisse alpha; Actins - metabolism; alpha-smooth muscle actin; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antioxidants (Nutrients); Biological markers; Biomarkers; Biomarkers - metabolism; Bone morphogenetic proteins; Collagen; Collagen Type I - metabolism; collagen-1 expression; Cytokines; Cytokines - metabolism; Dosage and administration; expression du collagène 1; fibrose hépatique; Fibrosis; Gene expression; Gene Expression - drug effects; Genes; Histochemistry; Histopathology; Hydroxyproline; Hydroxyproline - metabolism; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 1; Interleukin 10; Interleukin 6; Interleukin-10 - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; interleukine 10; Interleukins; Jewelry; Liver; Liver - drug effects; Liver - metabolism; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Liver diseases; liver fibrosis; Male; Muscle proteins; Muscles; Necrosis; Nitric oxide; Nitric Oxide - metabolism; Nitrogen oxides; Patient outcomes; Pharmacology; Phosphodiesterase; Physiology; Prevention; Rats; Rats, Wistar; Silymarin; Smooth muscle; Tadalafil; Tadalafil - pharmacology; Thioacetamide; Thioacetamide - pharmacology; thioacétamide; Transaminases - metabolism; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Tumors
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2018-0338

Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. This study aimed to explore the protective effect of tadalafil, a phosphodiesterase-5 inhibitor, against thioacetamide (TAA)-induced liver fibrosis. Fibrosis was induced by administration of TAA (200 mg/kg, i.p.) twice weekly for 6 weeks. Serum transaminases activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA induced marked histopathological changes in liver tissues coupled with elevations in serum transaminases activities. Furthermore, hepatic content of nitric oxide and tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta were elevated, together with a reduction of interleukin-10 in the liver. In addition, TAA increased hepatic contents of transforming growth factor-beta, hydroxyproline, alpha-smooth muscle actin, and gene expression of collagen-1. Pretreatment with tadalafil protected against TAA-induced liver fibrosis, in a dose-dependent manner, as proved by the alleviation of inflammatory and fibrotic biomarkers. The effects of tadalafil were comparable with that of silymarin, a natural antioxidant, and could be assigned to its anti-inflammatory and anti-fibrotic properties.