Denatonium Benzoate-Induces Oxidative Stress in the Heart and Kidney of Chinese Fast Yellow Chickens by Regulating Apoptosis, Autophagy, Antioxidative Activities and Bitter Taste Receptor Gene Expressions.

Enayatullah Hamdard,Mohammad Malyar Rahmani,Ahmadullah Zahir,Quanwei Wei,Fangxiong Shi,Zengpeng Lv,Zhicheng Shi

doi:10.3390/ani9090701

Enayatullah Hamdard, Mohammad Malyar Rahmani + Show 5 more

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https://doi.org/10.3390/ani9090701

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Abstract

Simple SummaryDenatonium benzoate is a strong bitter taste receptor agonist, extensively used for its activation of different cell pathways. Taste signals have been associated to food recognition and avoidance, and bitter taste provokes an aversive reaction and is assumed to protect chickens from consuming poisons and harmful toxic substances. The results of the study revealed that dietary supplementation with medium and high doses of denatonium benzoate damaged the epithelial cells of the heart and kidneys by inducing apoptosis and autophagy and reduced the growth of chickens, respectively. However, mRNA expressions of bitter taste receptors, downstream signaling effector genes, apoptosis-, autophagy- and antioxidant-related genes were higher on day 7, while these expressions were subsequently decreased on day-28 in the heart and kidney of Chinese Fast Yellow chickens in a dose-response manner.The sense of taste which tells us which prospective foods are nutritious, poisonous and harmful is essential for the life of the organisms. Denatonium benzoate (DB) is a bitter taste agonist known for its activation of bitter taste receptors in different cells. The aim of the current study was to investigate the mRNA expressions of bitter taste, downstream signaling effectors, apoptosis-, autophagy- and antioxidant-related genes and effector signaling pathways in the heart/kidney of chickens after DB dietary exposure. We randomly assigned 240, 1-day-old Chinese Fast Yellow chicks into four groups with five replicates of 12 chicks and studied them for 28 consecutive days. The dietary treatments consisted of basal diet and feed containing DB (5, 20 and 100 mg/kg). The results revealed that dietary DB impaired (p < 0.05) the growth performance of the chickens. Haemotoxylin and eosin staining and TUNEL assays confirmed that medium and high doses of DB damaged the epithelial cells of heart/kidney and induced apoptosis and autophagy. Remarkably, the results of RT-PCR and qRT-PCR indicated that different doses of DB gradually increased (p < 0.05) mRNA expressions of bitter taste, signaling effectors, apoptosis-, autophagy- and antioxidant- related genes on day 7 in a dose-response manner, while, these expressions were decreased (p < 0.05) subsequently by day-28 but exceptional higher (P < 0.05) expressions were observed in the high-dose DB groups of chickens. In conclusion, DB exerts adverse effects on the heart/kidney of chickens in a dose-response manner via damaging the epithelium of the heart/kidney by inducing apoptosis, autophagy associated with bitter taste and effector gene expressions. Correlation analyses for apoptosis/autophagy showed agonistic relationships. Our data provide a novel perspective for understanding the interaction of bitter taste, apoptosis, autophagy and antioxidative genes with bitter taste strong activators in the heart/kidney of chicken. These insights might help the feed industries and pave the way toward innovative directions in chicken husbandry.

Highlights

Taste is well-known biological descriptor for sweet, bitter, sour, salty receptors and ion channels, which plays a critical role in the life and nutritional status of chickens and other organisms
After continuous feeding for 28 consecutive days with Denatonium benzoate (DB)-containing diets or control, the body weights of Chinese Fast Yellow chickens were significantly decreased in the medium-dose (20 mg/kg) and high-dose (100 mg/kg) groups (p < 0.05), no differences were observed between control and the low-dose (5 mg/kg) groups (Figure 1)
The kidney weight gain on day-07 was similar in all DB-treated groups, interestingly the kidney weight gaining in comparison to heart weight gaining was higher in all groups

Summary

Introduction

Taste is well-known biological descriptor for sweet, bitter, sour, salty receptors and ion channels, which plays a critical role in the life and nutritional status of chickens and other organisms. Bitter taste receptors are part of a superfamily which includes more than twenty members. This makes very difficult to do functional studies for each bitter taste receptor. Bitter taste receptors expressions are not limited to taste buds and exist in extra-gustatory organs, so it is critical to determine their extra-gustatory functions. Several studies have already revealed that bitter taste receptors exert a variety of functions in different cells and tissues [7,8]. It has been reported that this receptor family plays a critical role in the heart [10], thyroid [11], and gastrointestinal muscle [12]

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