Impact of High Fat- and High Fructose-Diet on Murine Hepatic Histological Feature and CYP3A11 Profile

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Nattharat Jearapong
Waranya Chatuphonprasert
Kanokwan Jarukamjorn

Abstract

Introduction: Fructose and hydrogenated oil are appeared together as ingredients in several processed food, in which consumption of those is a risk factor to develop metabolic diseases. Liver is a major organ which is impacted by these diets. Cytochrome P450 3A (CYP3A) is a major hepatic cytochrome P450 enzyme that takes responsible for metabolism of almost clinical drugs. The present study aimed to investigate hepatic histopathology and CYP3A11 pattern in mice fed with high fat- and high fructose-diet (HFFD). Methods: Seven-week-old male ICR mice (n=5) were intragastrically administered hydrogenated soybean oil (1 mL/day/mouse) with free access to 20% (w/v) aqueous fructose solution for 2, 4, and 8 weeks. The protein expression and catalytic activity of CYP3A11 were determined employing immunoblotting techniques and a specific reaction of erythromycin N-demethylation (ENDM), respectively. Results: Karyorrhexis and pyknosis of nuclei were detected after the HFFD feeding for 4 weeks while Kupffer cells in sinusoid and microvesicular hepatocytes were observed after 8 weeks of the induction. The change of hepatic histomorphological features was correlated with an increase in the protein level and catalytic activity of CYP3A11. Moreover, the HFFD-fed mice were increased in the fasting blood glucose level and AUC in the oral glucose tolerance test at the end of the study. Conclusion: High fat- and high fructose-consumption worsen the physiological feature of hepatic tissue along with induction of murine CYP3A11 profile, though it did not affect the weight gaining. Hence, a person with long-term consumption of high fat- and/or high fructose-diet has a risk of hepatic pathology and induction of CYP3A11 expression, leading to alter drug metabolism and extensive risk of drug interaction.

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Pharmaceutical Sciences

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