Pharmacological evaluation of pioglitazone and candesartan cilexetil in a novel mouse model of non‐alcoholic steatohepatitis, modified choline‐deficient, amino acid‐defined diet fed low‐density lipoprotein receptor knockout mice

Abstract

Pioglitazone showed anti-fibrotic effects accompanied by improving hepatic transaminase activity and hepatic lipid accumulation, but the effect of candesartan cilexetil was only limited, unlike previous reports for angiotensin II type 1 receptor blockers. As the pharmacological effects of pioglitazone in the current animal model are similar to those reported in patients with NASH, this model may represent some aspects of the pathophysiology of NASH. Further profiling using other agents or mechanisms that have been tested in the clinic will better clarify the utility of the animal model.

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

“…Drug therapy is still the main option to control NASH progression [8,9,10]. The common drugs for NASH treatment are vitamin E [11], pioglitazone [12], peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ agonist [13], etc. Vitamin E has antioxidant activities and is widely used for treating chronic liver disorders.…”

Validation of a diet‐induced Macaca fascicularis model of non‐alcoholic steatohepatitis with dietary and pioglitazone interventions

“…Multiple compounds that failed in phase 3 trials (elafibrinor, 37 firsocostat, 38 cilofexor, 39 aramchol, 40 cenicrivoroc 41 ) all showed efficacy in rodent models, but were not tested (or reported to be) in NHP models of NASH. A switch from either a high fat 42 or a high sucrose/high fat diet 43 to a chow diet, or alternative approaches to reduce body weight such as Roux‐en‐Y gastric bypass (inducing 25% weight loss 44 ), and treatment with pioglitazone, 45‐47 have all been shown to improve histology in mouse models of NASH. However, 25% CR resulting in 10% weight loss did not improve NASH in the genetic foz/foz mouse model 48 .…”

“…32 The data for humans and monkeys were fit using the equation ΔLiver fat(%) = β 1 (1 À exp(Àβ 2 *ΔBW(%)), with similar estimates of β 1 = 100 ± 40 in humans versus 89 ± 15 in monkeys and β 2 = 0.09 ± 0.06 in humans versus 0.11 ± 0.03 in monkeys. ANOVA, analysis of variance; NHP, non-human primate diet 43 to a chow diet, or alternative approaches to reduce body weight such as Roux-en-Y gastric bypass (inducing 25% weight loss 44 ), and treatment with pioglitazone, [45][46][47] have all been shown to improve histology in mouse models of NASH. However, 25% CR resulting in 10% weight loss did not improve NASH in the genetic foz/foz mouse model.…”

Polydatin inhibits ZEB1‐invoked epithelial‐mesenchymal transition in fructose‐induced liver fibrosis

“…It also inhibits TGF‐β1 and collagen, reduces TGF‐β1‐induced EMT in human alveolar epithelium A549 cells 37 and protects against methionine‐choline deficient diet‐induced mouse liver fibrosis 21 . Pioglitazone decreases hepatic TGF‐β1 and COL1A1 in non‐alcoholic steatohepatitis of mice 38,39 . In this study, polydatin and pioglitazone effectively down‐regulated survivin to inhibit the activation of TGF‐β1/Smad signalling and repress the EMT, preventing against fructose‐caused liver fibrosis.…”