Antifibrotic effects of bezafibrate and pioglitazone against thioacetamide-induced liver fibrosis in albino rats

Publication: Canadian Journal of Physiology and Pharmacology
28 July 2020

Abstract

Activation of hepatic stellate cells is a central event in hepatic fibrogenesis that offers multiple potential sites for therapeutic interventions. Peroxisome proliferator-activated receptors are implicated in liver fibrosis. We aimed to evaluate the effect of bezafibrate and pioglitazone on a thioacetamide (TAA) rat model of liver fibrosis and to clarify the possible underlying mechanisms. Rats received intraperitoneal injections of TAA for 6 weeks. Daily oral treatments with bezafibrate or pioglitazone were started with the first day of TAA intoxication. Serum liver function tests, hepatic malondialdehyde (MDA), total nitrite and nitrate (NOx), superoxide dismutase, and hepatic histopathology were assessed to evaluate hepatic damage. Alpha smooth muscle actin (α-SMA) and tissue inhibitor metalloproteinase-1 (TIMP-1) and caspase-3 were also assessed. The TAA group experienced significant deterioration of liver functions, increased oxidative stress, and increased liver tissue NOx. Administration of bezafibrate or pioglitazone resulted in significant improvement of all liver functions and reduced oxidative stress in hepatic tissues. Only administration of bezafibrate significantly reduced NOx levels. Liver tissues from the TAA-treated group showed disrupted normal architecture. Administration of bezafibrate or pioglitazone attenuated this picture. Stronger α-SMA expression was detected in the TAA group. Treatment with bezafibrate or pioglitazone decreased the α-SMA expression.

Résumé

L’activation des cellules de Küpfer constitue un événement central de la fibrogenèse hépatique qui offre de multiples possibilités de sites d’interventions thérapeutiques. Les récepteurs activés par les proliférateurs des peroxysomes jouent un rôle dans la fibrose hépatique. Nous visions à évaluer les effets du bézafibrate et de la pioglitazone dans un modèle de fibrose hépatique produit par le thioacétamide (TAA) chez le rat en vue de clarifier les modes d’action sous-jacents éventuels. Nous avons injecté du TAA par voie intrapéritonéale chez les rats pendant 6 semaines. Nous avons commencé l’administration quotidienne de bézafibrate ou de pioglitazone par voie orale au premier jour de l’intoxication par le TAA. Nous avons évalué les dommages hépatiques à l’aide de tests sériques de la fonction hépatique et des taux hépatiques de malondialdéhyde (MDA), ainsi que des taux totaux de nitrite et de nitrates (NOx), ainsi que de superoxyde dismutase, et avec une étude histopathologique du foie. Nous avons aussi évalué les taux d’actine du muscle lisse (α-SMA), de l’inhibiteur tissulaire de la metalloprotéinase 1 (TIMP-1) et de la caspase-3. Le groupe TAA a présenté une détérioration du fonctionnement du foie, un accroissement du stress oxydatif, avec une hausse des NOx appréciables dans le tissu hépatique. L’administration de bézafibrate ou de pioglitazone a permis d’améliorer l’ensemble du fonctionnement du foie avec une diminution du stress oxydatif dans le tissu hépatique. Cependant, uniquement l’administration de bézafibrate a entraîné une diminution notable des taux de NOx. Nous avons observé des perturbations de l’architecture normale du tissu hépatique dans le groupe TAA. L’administration de bézafibrate ou de pioglitazone permettait d’améliorer ce tableau. Nous avons décelé une augmentation de l’expression de l’α-SMA dans le groupe TAA. L’administration de bézafibrate ou de pioglitazone entraînait une diminution de l’expression de l’α-SMA. [Traduit par la Rédaction]

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Published In

cover image Canadian Journal of Physiology and Pharmacology
Canadian Journal of Physiology and Pharmacology
Volume 99Number 3March 2021
Pages: 313 - 320

History

Received: 25 March 2020
Accepted: 12 July 2020
Published online: 28 July 2020

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Key Words

  1. bezafibrate
  2. pioglitazone
  3. liver fibrosis
  4. thioacetamide
  5. antioxidants
  6. PPAR
  7. antifibrotic

Mots-clés

  1. bézafibrate
  2. pioglitazone
  3. fibrose hépatique
  4. thioacétamide
  5. antioxydants
  6. récepteurs activés par les proliférateurs des peroxysomes (PPAR)
  7. antifibrosant

Authors

Affiliations

Department of Pharmacology, Minia University Faculty of Medicine, Minia, Egypt.
Mervat Z. Mohamed
Department of Pharmacology, Minia University Faculty of Medicine, Minia, Egypt.
Nashwa F. El-Tahawy
Department of Histology & Cell Biology, Minia University Faculty of Medicine, Minia, Egypt.
Aly M. Abdelrahman
Department of Pharmacology, Minia University Faculty of Medicine, Minia, Egypt.

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