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Effects of DB supplementation on the histomorphology of chicken kidney on day-07 and day-28 (A,B). On day-07, the black arrow shows that PCTs became swollen (hydrophiid degeneration). The white arrow indicates inflamed infiltrated cells and the green arrow indicates separation of the basement membrane of DCTs; Karyolysis occurred where no cells were found due to the toxic effects of DB. The effects on day 28 showed no major differences.
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Simple Summary
Denatonium 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...
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... Dietary administration of denatonium benzoate over 28 or 56 days in the chickens induced apoptosis and upregulated T2R receptors and signaling proteins. In a similar study, long-term dietary administration of denatonium benzoate also induced apoptosis in the heart and kidney of Chinese fast yellow chickens [177]. Denatonium benzoate also increased T2R expression, antioxidant stress, and autophagy in these organs. ...
Humans can perceive five canonical tastes: salty, sour, umami, sweet, and bitter. These tastes are transmitted through the activation of ion channels and receptors. Bitter taste receptors (Taste Family 2 Receptors; T2Rs) are a sub-family of 25 G-protein coupled receptor (GPCR) isoforms that were first identified in type II taste bud cells. T2Rs are activated by a broad array of bitter agonists, which cause an increase in intracellular calcium (Ca²⁺) and a decrease in cyclic adenosine 3’,5’-monophosphate (cAMP). Interestingly, T2Rs are expressed beyond the oral cavity, where they play diverse non-taste roles in cell physiology and disease. Here, we summarize the literature that explores the role of T2Rs in apoptosis. Activation of T2Rs with bitter agonists induces apoptosis in several cancers, the airway epithelia, smooth muscle, and more. In many of these tissues, T2R activation causes mitochondrial Ca²⁺ overload, a main driver of apoptosis. This response may be a result of T2R cellular localization, nuclear Ca²⁺ mobilization and/or a remnant of the established immunological roles of T2Rs in other cell types. T2R-induced apoptosis could be pharmacologically leveraged to treat diseases of altered cellular proliferation. Future work must explore additional extra-oral T2R-expressing tissues for apoptotic responses, develop methods for in-vivo studies, and discover high affinity bitter agonists for clinical application.
... TAS2Rs are expressed in blood monocytes or monocyte-derived macrophages (Grassin-Delyle et al. 2019), neutrophils (Maurer et al. 2015), keratinocytes (Wölfle et al. 2015), thymus (Panneck et al. 2014;Soultanova et al. 2015), vascular smooth muscles (Lund et al. 2013), pancreas (Gaida et al. 2016), brain (Singh et al. 2011), thyroid gland (Clark et al. 2015), testis (Xu et al. 2013), spermatozoa (Governini et al. 2020), prostate (Dupre and Martin 2017;Martin et al. 2019), vagina, cervix, endometrium, myometrium, placenta, ovary (Dupre and Martin 2017;Welcome 2020a), urethra, ureter, bladder (Welcome 2020a;, and kidney (Liu et al. 2015b). Relatively more recently, independent groups of researchers have identified the expression of TAS2Rs in cells and tissues of the heart (Foster et al. 2013(Foster et al. , 2014Manson et al. 2014), indicating that these receptors may be involved in mediating the inflammatory, oxidative stress responses, autophagy (Hamdard et al. 2019b), cardiac rhythm (Yuan et al. 2020) and contractile activities (Manson et al. 2014;Bloxham et al. 2020;Yuan et al. 2020) in this vital organ. ...
... Indeed, some phytochemicals and their derivatives acting as TAS2R agonists have been identified as promising therapeutic agents for potential treatment of several disorders, including heart diseases (vide infra) (Kamila and Agnieszka 2021). Therefore, research has revealed that denatonium benzoate, an agonist of TAS2R1, 2, 7, and α-gustducin, at low dose (5 mg/kg) and short period of treatment (i.e. 7 days) causes a decrease in the expression of apoptosis and autophagy-related genes-caspase (Casp) 2, Casp3, Casp7, Casp9, Bcl-2l1 (B cell lymphoma 2 like 1), Mcl (mantle cell lymphoma), Bid (BH3-interacting domain death agonist), and Noxa (NADPH oxidase activator), along with increased expression of antioxidant enzymes or mediators such as glutathione peroxidase 1 (Gpx1), catalase (CAT), superoxide dismutase 1 (SOD1) and calpain-1 in whole heart tissues of experimental animals (Hamdard et al. 2019b). However, at higher doses and chronic treatment with denatonium benzoate, Hamdard et al. (2019a, b) demonstrated increased expression of the apoptosis and autophagy-related genes, suggesting that TAS2R activation may be beneficial at low doses and acute treatment period (Hamdard et al. 2019b). ...
... Therefore, research has revealed that denatonium benzoate, an agonist of TAS2R1, 2, 7, and α-gustducin, at low dose (5 mg/kg) and short period of treatment (i.e. 7 days) causes a decrease in the expression of apoptosis and autophagy-related genes-caspase (Casp) 2, Casp3, Casp7, Casp9, Bcl-2l1 (B cell lymphoma 2 like 1), Mcl (mantle cell lymphoma), Bid (BH3-interacting domain death agonist), and Noxa (NADPH oxidase activator), along with increased expression of antioxidant enzymes or mediators such as glutathione peroxidase 1 (Gpx1), catalase (CAT), superoxide dismutase 1 (SOD1) and calpain-1 in whole heart tissues of experimental animals (Hamdard et al. 2019b). However, at higher doses and chronic treatment with denatonium benzoate, Hamdard et al. (2019a, b) demonstrated increased expression of the apoptosis and autophagy-related genes, suggesting that TAS2R activation may be beneficial at low doses and acute treatment period (Hamdard et al. 2019b). ...
Heart diseases and related complications constitute a leading cause of death and socioeconomic threat worldwide. Despite intense efforts and research on the pathogenetic mechanisms of these diseases, the underlying cellular and molecular mechanisms are yet to be completely understood. Several lines of evidence indicate a critical role of inflammatory and oxidative stress responses in the development and progression of heart diseases. Nevertheless, the molecular machinery that drives cardiac inflammation and oxidative stress is not completely known. Recent data suggest an important role of cardiac bitter taste receptors (TAS2Rs) in the pathogenetic mechanism of heart diseases. Independent groups of researchers have demonstrated a central role of TAS2Rs in mediating inflammatory, oxidative stress responses, autophagy, impulse generation/propagation and contractile activities in the heart, suggesting that dysfunctional TAS2R signalling may predispose to cardiac inflammatory and oxidative stress disorders, characterised by contractile dysfunction and arrhythmia. Moreover, cardiac TAS2Rs act as gateway surveillance units that monitor and detect toxigenic or pathogenic molecules, including microbial components, and initiate responses that ultimately culminate in protection of the host against the aggression. Unfortunately, however, the molecular mechanisms that link TAS2R sensing of the cardiac milieu to inflammatory and oxidative stress responses are not clearly known. Therefore, we sought to review the possible role of TAS2R signalling in the pathophysiology of cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases. Potential therapeutic significance of targeting TAS2R or its downstream signalling molecules in cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction is also discussed.
... Eggs that are obsolete and unusable by humans are used for livestock. Studies have shown that chickens are more susceptible to malnutrition than other animals [8][9][10]. Poultry is also more valuable due to its low cost, abundance, breeding method and short duration and used in research and many researchers believe that poultry needs are similar to human needs and that other animals (cattle and sheep) are less expensive and more economical in the short term [4]. ...
... Eggs that are obsolete and unusable by humans are used for livestock. Studies have shown that chickens are more susceptible to malnutrition than other animals [8][9][10]. Poultry is also more valuable due to its low cost, abundance, breeding method and short duration and used in research and many researchers believe that poultry needs are similar to human needs and that other animals (cattle and sheep) are less expensive and more economical in the short term [4]. ...
A study was conducted in Baghlan province to compare foreign and domestic poultry feeds on Golden Egg Layers. The study was started on 2019/09/15 and took 2.5 months. A small farm of 40 chickens was formed and the chickens were divided randomly into four equal groups (A, B, C and D). Each group of 10 chicks was housed in a special cage, and all environmental conditions such as humidity, heat, light, and darkness were kept constant during the entire period of experiment. Completely randomized research design (CRD) was adopted for the study. Groups A, B, C and D were fed feeds from Iran Shams Farahi company, Pakistan Islamabad company, Kabul Feed company and Jalalabad Habib Hussam company, respectively. The results revealed, there was no Original Research Article Abozar et al.; AJRAVS, 7(2): 1-14, 2021; Article no.AJRAVS.64812 2 significant difference in weight gain during the first three weeks. However, from the third week onwards there was a significant difference (p<0.05) between weights gains dietary efficiency per kilogram of body consumed. For gaining 1 Kg body weight during 3 weeks, the pullets consumed 11065 gram Islamabad company feed, 11295 gram Iran Shams Farahi company feed, 11656 gram Kabul company feed and 12945 gram Habib Hussam company feed. From the study it is clear that Islamabad company feed is more economical and effective feed as compared to feed from other three companies. A group produced 15 eggs, B group produced 129 eggs, C group produced 121 eggs and D group produced 136 eggs. Therefore, it is concluded that group B, managed on feed from Islamabad company produced significantly higher number of eggs than other three groups. In term of economical state, the net profit of Islamabad feed was 654.95 AFN, Jalalabad Habib Hussam feed 247.9 AFN, Kabul feed 229.5 AFN and Iran Shams Farahi feed was 135 AFN. Therefore, it is concluded. that the order of effectiveness (descending order) of the poultry feeds was Islamabad company of Pakistan followed by Jalalabad Habib Hussam, Kabul Feed Company and Iran Shams Farahi Company.
... In chicken bitter is the most crucial biological taste disruptor, it provokes chickens against consuming hazard and destructive foods prior to ingestion and therefore considered as a cautionary indicator. which tells chicken which prospective foods are nutritious, poisonous/toxic, harmful and these taste indications have been linked/associated to food identification, recognition and avoidance [1,2]. ...
... The obtained tissue sections were collected on glass slides, deparaffinized and stained by hematoxylin and eosin stain for histopathological examination. Five sections of testis from each of three different doses were observed for the histological changes in the seminiferous tubules as the previous method reported [28][29][30][31]. (Total of 30 sections were observed from each mouse). ...
Simple Summary
Spermatogenesis and hormones secretions are serious life-threating and complicated process, which can be improve through science-based approaches. Royal jelly is a thick white milky fluid secreted by the hypopharyngeal and mandibular glands of young nurse worker bees (Apis mellifera) and used to feed their queen to expand their life. The results of the study revealed that, the growth performance of testis in exposed mice to freeze-dried Royal Jelly for 35 consecutive days were significantly enhanced in moderate dose among other treated doses. However, at Post Natal Days (PNDs 14 and PNDs 21), obviously changes were observed in histological examination of the testis while at PNDs-07 no major changes were observed. The Tunnel assay showed that, less apoptotic cells were detected in the testis of mice in high dose of freeze-dried RJ and oral administration of freeze-dried royal jelly can aggravate adverse effects via tempestuous on sexual hormone secretion at both PNDs 21 and PNDs 35 respectively.
Abstract
Spermatogenesis and hormones secretions are crucial endocrine and physiological process for maintaining the life. Royal Jelly (RJ) bioactive components are Major Royal Jelly Proteins (MRJPs), owing exceptional biological properties. However, the effects of RJ on pup’s testicular development during neonatal and pubertal period exposure hasn’t been adequately studied. The aim of the study was to detect neonatal sexual hormones concentration and histopathological changes on testicular development of the male progeny after oral exposure to freeze-dried RJ for 35 consecutive days. After mice give birth, male pups were collected together, separated by sex, and randomly standardized to seven (7) male pups per dam. Male pups were assigned to control diet (CON group), low dose RJ (L-RJ group) diet (control diet + 125 mg/kg/day RJ), moderate dose RJ (M-RJ group) diet (control diet + 250 mg/kg/day RJ) and high dose of RJ (H-RJ group) diet (control diet + 500 mg/kg/day RJ). After weaning, male pups were continuously fed with freeze-dried RJ until the age of PNDs 35. The results revealed that, oral M-RJ (250 mg/kg/day) administration significantly (p < 0.05) increased the testis weight, the diameter of seminiferous tubule and the height of seminiferous epithelium of offspring mice at PNDs 14. However, high-dose RJ (500 mg/kg/day) decreased the diameter of seminiferous tubule but increased the height of seminiferous epithelium of male offspring (p < 0.05) at the same time point. Furthermore, oral M-RJ treatment significantly (p < 0.05) increased the testis weight and spermatogenesis at PNDs 21. Whereas, oral H-RJ treatment significantly (p < 0.05) reduced the diameter of seminiferous tubule and the height of seminiferous epithelium at PNDs 21. At PNDs 35, oral M-RJ treatment increased the testis weight, the diameter of seminiferous tubule and the level of FSH. While, high-dose of RJ reduced testis weight and size (diameter of seminiferous tubule and height of seminiferous epithelium), ratio of apoptotic germ cells and incomplete spermatogenesis collectively. In addition, sexual hormone secretions (FSH, LH, E2) were decreased after RJs treatment (L-RJ, M-RJ, H-RJ) at PNDs 21 respectively. In conclusion, the results concluded that oral administration of low and moderate doses of RJ could enhance the development of testis at neonate period until pubescent, whereas unfavorable adverse effects induced by high dose of RJ might remain.
Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C β2 (PLCβ2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCβ2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gβγ inhibitor Gallein, or a PLCβ2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease.
G protein‐coupled receptors (GPCRs) constitute the largest and most diverse superfamily of mammalian transmembrane proteins. These receptors are involved in a wide range of physiological functions and are targets for more than a third of available drugs in the market. Autophagy is a cellular process involved in degrading damaged proteins and organelles and in recycling cellular components. Deficiencies in autophagy are involved in a variety of pathological conditions. Both GPCRs and autophagy are essential in preserving homeostasis and cell survival. There is emerging evidence suggesting that GPCRs are direct regulators of autophagy. Additionally, autophagic machinery is involved in the regulation of GPCR signalling. The interplay between GPCR and autophagic signalling mechanisms significantly impacts on health and disease; however, there is still an incomplete understanding of the underlying mechanisms and therapeutic implications in different tissues and disease contexts. This review aims to discuss the interactions between GPCR and autophagy signalling. Studies on muscarinic receptors, beta‐adrenoceptors, taste receptors, purinergic receptors and adhesion GPCRs are summarized, in relation to autophagy.
Bitter taste receptors (T2Rs) localize to airway motile cilia and initiate innate immune responses in retaliation to bacterial quorum sensing molecules. Activation of cilia T2Rs leads to calcium-driven NO production that increases cilia beating and directly kills bacteria. Several diseases, including chronic rhinosinusitis, COPD, and cystic fibrosis, are characterized by loss of motile cilia and/or squamous metaplasia. To understand T2R function within the altered landscape of airway disease, we studied T2Rs in non-ciliated airway cell lines and primary cells. Several T2Rs localize to the nucleus in de-differentiated but localize to cilia in differentiated cells. As cilia and nuclear import utilize shared proteins, some T2Rs may target to the nucleus in the absence of motile cilia. T2R agonists selectively elevated nuclear and mitochondrial calcium through a G-protein-coupled receptor phospholipase C mechanism. Additionally, T2R agonists decreased nuclear cAMP, increased nitric oxide, and increased cGMP, consistent with T2R signaling. Furthermore, exposure to T2R agonists led to nuclear calcium-induced mitochondrial depolarization and caspase activation. T2R agonists induced apoptosis in primary bronchial and nasal cells differentiated at air-liquid interface but then induced to a squamous phenotype by apical submersion. Air-exposed well-differentiated cells did not die. This may be a last-resort defense against bacterial infection. However, it may also increase susceptibility of de-differentiated or remodeled epithelia to damage by bacterial metabolites. Moreover, the T2R-activated apoptosis pathway occurs in airway cancer cells. T2Rs may thus contribute to microbiome-tumor cell crosstalk in airway cancers. Targeting T2Rs may be useful for activating cancer cell apoptosis while sparing surrounding tissue.
