In Vitro and In Vivo Study on the Toxic Effects of Propiconazole Fungicide in the Pathogenesis of Liver Fibrosis

Abstract

Propiconazole (PCZ) is a hepatotoxic triazole fungicide. There are insufficient data on how PCZ induces liver fibrosis in humans. This study aimed to investigate the effect of PCZ on liver fibrosis and its underlying mechanisms. HepG2 cells and Sprague−Dawley rats were exposed to PCZ at doses of 0−160 μM (3−72 h) and 0.5−50 mg/kg body weight/day (28 days), respectively. PCZ-treated cells activated intracellular oxidative stress via cytochrome P450 and had higher mRNA levels of interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, and transforming growth factor-β (TGF-β) than the control. PCZ treatment in cells induced a morphological transition with E-cadherin decrease and vimentin and Snail increase via the oxidative stress and TGF-β/Smad pathways. PCZ administration in rats induced liver fibrosis through pathological changes, epithelial−mesenchymal transition, and collagen deposition. Thus, our data suggest that exposure of PCZ to humans may be a risk factor for the functional integrity of the liver.

Effect of Pesticide Residue in Muscle and Fat Tissue of Pigs Treated with Propiconazole

“…The effects of treating pigs with propiconazole for 28 d on the growth performance of finishing pigs are summarized in Table 2 . A previous studies showed that propiconazole did not effect on body weight in Sprague–Dawley rats ( Costa et al, 2015 ; Kwon et al, 2021 ) and mice ( Sun et al, 2005 ). Therefore, the body weight (initial and final), average daily weight gain, average daily feed intake, and feed conversion ratio were not affected by propiconazole exposure.…”

“…Thus, propiconazole affects the expression of fibrosis-related genes, while not affecting Activin A receptor type 2A (Acta2a) and TIMP metallopeptidase inhibitor 1 (TIMP1) gene expression (data not shown). The exposed to propiconazole to human liver cells and rat liver can lead to liver fibrosis ( Kwon et al, 2021 ). Activation of TGFb1/Smad signaling is known as inducer of kidney fibrosis ( Meng et al, 2015 ).…”

Effect of Flutriafol Exposure on Residue Characteristics in Pig Muscle and Fat Tissue

“…Flutriafol, known as conazole fungicide, is used to control leaf and ear diseases in cereals ( FAO, 2011 ) and to prevent fungal diseases ( Bhuiyan et al, 2015 ; Lass-Flörl, 2011 ). Exposure to pesticides through oral, dermal, or inhalation routes is associated with low or moderate toxicity ( Kwon et al, 2021b ; Shahinasi et al, 2017 ; Toumi et al, 2017 ). The high performance liquid chromatography method was used to establish the maximum residue limits of flutriafol exposure in wheat and soil ( Yu et al., 2012 ; Zhang et al, 2014 ).…”

“…Exposure to ethylated dialkylphosphates, which are known to have immunomodulatory potential, can induce long-term damage to the heart, leading to fibrosis ( Medina-Buelvas et al, 2019 ). Exposure to residual pesticides increased liver fibrosis and nonalcoholic fatty liver disease in HepG2 cells and rat liver ( Kwon et al, 2021a ; Kwon et al, 2021b ). Furthermore, meta-analysis revealed that the risk of idiopathic pulmonary fibrosis increased in agricultural workers exposed to pesticides ( Park et al, 2021 ; Ramani et al, 2021 ).…”

Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

“…A previous study showed that insecticide exposure impaired lipid metabolism, thereby resulting in the development of NAFLD [21]. Moreover, recent studies have reported that fungicides such as propiconazole, flutriafol, cyproconazole, dazomet, fluazinam, hexaconazole, pyrasulfotole metabolite, and myclobutanil can cause NAFLD pathogenesis [22][23][24][25]. However, the toxic effects of TEB on lipid accumulation and lipid metabolism in the liver have rarely been studied.…”