Arecoline inhibits pineal-testis function in experimentally induced hypothyroid rats.
01 Jan 2020-Archives of Physiology and Biochemistry (Arch Physiol Biochem)-Vol. 126, Iss: 1, pp 7-16
TL;DR: It is suggested that arecoline inhibits pineal–testis function in experimentally induced hypothyroid rats.
Abstract: Arecoline is known to cause endocrine dysfunction. In the current article role of arecoline on pineal-testis activity was investigated in hypothyroid rats induced by propylthiouracil (PTU). PTU treatment caused thyroid dysfunction ultrastructurally with a fall in T3 and T4 levels followed by a rise of thyroid stimulating hormone (TSH) level. Pineal activity was impaired by PTU treatment, as evident from degenerated synaptic ribbons and mitochondria of the pinealocytes with depletion of pineal and serum N-acetyl serotonin and melatonin levels. Leydig cell function was suppressed, evident from reduced smooth endoplasmic reticulum and depletion of testosterone level. Sex accessories function was impaired by showing scanty rough endoplasmic reticulum with depletion of fructose and sialic acid levels. Arecoline treatment that caused pineal dysfunction and testicular stimulation in control rats, suppressed both pineal and testis functions after PTU treatment. The findings suggest that arecoline inhibits pineal-testis function in experimentally induced hypothyroid rats.
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TL;DR: The importance of arecoline is supported by its being the world's fourth most commonly used human psychoactive substance (after alcohol, nicotine, and caffeine) and social and historical aspects of its use and abuse.
Abstract: Arecoline is a naturally occurring psychoactive alkaloid from areca (betel) nuts of the areca palm ( Areca catechu) endemic to South and Southeast Asia. A partial agonist of nicotinic and muscarinic acetylcholine receptors, arecoline evokes multiple effects on the central nervous system (CNS), including stimulation, alertness, elation, and anxiolysis. Like nicotine, arecoline also evokes addiction and withdrawal symptoms (upon discontinuation). The abuse of areca nuts is widespread, with over 600 million users globally. The importance of arecoline is further supported by its being the world's fourth most commonly used human psychoactive substance (after alcohol, nicotine, and caffeine). Here, we discuss neuropharmacology, pharmacokinetics, and metabolism of arecoline, as well as social and historical aspects of its use and abuse. Paralleling clinical findings, we also evaluate its effects in animal models and outline future clinical and preclinical CNS research in this field.
37 citations
Dissertation•
01 Jan 2005
25 citations
TL;DR: AlA supplementation ameliorated the toxicity induced by hypothyroidism as illustrated by enhanced reproductive organ weights, testosterone, LH, and FSH levels, testicular steroidogenesis, and oxidative stress parameters.
Abstract: Background: The objective of this study is to evaluate the influence of carbimazole- induced hypothyroidism on the testes of adult albino rats and the probable protective effect of alpha-lipoic acid (ALA). Materials and methods: The rats were divided into four groups; control group, ALA group, carbimazole, and carbimazole + ALA groups. Rats were exposed to ALA (60 mg/kg body weight) or carbimazole (1.35 mg/kg body weight), or both, administered via gavages for 30 days. Results: Morphometric analysis revealed a significant decrease in tubular diameter, germinal epithelium thickness, and interstitial space as compared to the controls. Also, rats exposed to carbimazole showed a significant decline in testicular weight, sperm motility, and count. Additionally, deterioration of the testicular architecture was observed. ALA supplementation resulted in a significant improvement in the tubular diameter and germinal epithelium thickness, but no significant improvement regarding interstitial space was observed. Another observation was the significant decline in serum testosterone and follicle-stimulating hormone (FSH) in the carbimazole group, indicating reduced steroidogenesis. A significant reduction in reduced glutathione content was detected in the testes of the carbimazole group compared with the controls, while malonaldehyde concentration significantly increased. Conversely, ALA supplementation ameliorated the toxicity induced by hypothyroidism as illustrated by enhanced reproductive organ weights, testosterone, luteinizing hormone, and FSH levels, testicular steroidogenesis, and oxidative stress parameters. Conclusions: Hypothyroidism altered testicular antioxidant balance and negatively affected spermatogenesis. On the other hand, ALA through its antioxidant properties alleviated testicular toxicity in carbimazole-exposed rats.
16 citations
Cites background from "Arecoline inhibits pineal-testis fu..."
...PTU-induced hypothyroidism significantly decreased serum levels of both T3 and T4 while, increased TSH level [36]....
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TL;DR: New insights into the underlying pathogenesis of RA and OA are suggested, which may improve the diagnosis and treatment of these intractable chronic diseases.
Abstract: Background Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases. The present study aimed to identify hub genes involved in the pathogenesis and further explore the potential treatment targets of RA and OA. Methods The gene expression profile of GSE12021 was downloaded from Gene Expression Omnibus (GEO). Total 31 samples (12 RA, 10 OA and 9 NC samples) were used. The differentially expressed genes (DEGs) in RA versus NC, OA versus NC and RA versus OA groups were screened using limma package. We also verified the DEGs in GSE55235 and GSE100786. Functional annotation and protein-protein interaction (PPI) network construction of OA- and RA-specific DEGs were performed. Finally, the candidate small molecules as potential drugs to treat RA and OA were predicted in CMap database. Results 165 up-regulated and 163 down-regulated DEGs between RA and NC samples, 73 up-regulated and 293 down-regulated DEGs between OA and NC samples, 92 up-regulated and 98 down-regulated DEGs between RA and OA samples were identified. Immune response and TNF signaling pathway were significantly enriched pathways for RA- and OA-specific DEGs, respectively. The hub genes were mainly associated with 'Primary immunodeficiency' (RA vs. NC group), 'Ribosome' (OA vs. NC group), and 'Chemokine signaling pathway' (RA vs. OA group). Arecoline and Cefamandole were the most promising small molecule to reverse the RA and OA gene expression. Conclusion Our findings suggest new insights into the underlying pathogenesis of RA and OA, which may improve the diagnosis and treatment of these intractable chronic diseases.
7 citations
TL;DR: It confirms that Fr-II synergizes with TMZ to significantly intensify its anti-proliferative properties, thereby emerging as an effective element for combinatorial treatment of glioblastoma.
Abstract: Objective: This study was designed to analyze the combinatorial chemotherapeutic effect of temozolomide (TMZ), the most common drug in glioblastoma treatment and a purified carbohydrate (Fr-II) from the edible mushroom Pleurotus florida , on human glioblastoma cell lines Methods: Fr-II was purified by size-exclusion chromatography and characterised by different mass spectroscopy analysis Human glioblastoma cells were treated with TMZ, Fr-II, and combination of TMZ and Fr-II Cell cytotoxicity was measured by MTT assay, cell cycle phase distribution was determined by cell cycle analysis and followed by the relative p53 protein expression was analyzed by western blot analysis Results: Chemical analysis of Fr-II confirmed the glycosidically linked two units of glucose with terminally attached mannitol with mass of 506 Da Fr-II treatment exhibited cytotoxicity in both the cell lines in a dose-dependent manner with most effective dose at 200µg/ml When Fr-II (200µg/ml) was combined with a dose range of TMZ it showed a more cellular cytotoxicity compared to the cytotoxicity of TMZ alone with most oppressive combinatorial dose at 400µM (TMZ)+200µg/ml (Fr-II) In compliance, with the above results, both cell lines showed a 10% increase in no of cells (p<005) in G 2 /M phase indicating an arrest of cell cycle and increased p53 protein expression (p<005) at the combinatorial dose than TMZ alone at 400µM, but Fr-II alone didn’t show any cell cycle arrest nor did it show increased p53 expression Conclusion: Therefore it confirms that Fr-II synergizes with TMZ to significantly intensify its anti-proliferative properties, thereby emerging as an effective element for combinatorial treatment of glioblastoma
3 citations
References
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TL;DR: It appears from this study that the close metabolic relationship between the liver/kidney and the thyroid should be taken into consideration when the findings of chronic toxicology and carcinogenicity studies are interpreted.
64 citations
61 citations
"Arecoline inhibits pineal-testis fu..." refers methods in this paper
...The colour development was stopped with addition of the stop solution (dilute sulphuric acid) and the absorbance was measured by ELISA Reader (Qualigen Plate Reader PR601, UK) at 450 nm....
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...Serum testosterone concentration was assayed by ELISA on the principle of competitive binding between testosterone in the test specimen and testosterone-HRP conjugate for a constant amount of rabbit anti-testosterone....
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...Serum testosterone level was assayed by ELISA (Chen et al. 1991) using the pathozyme testosterone kit (Product code OD497) of OMEGA, UK....
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TL;DR: The present results suggest that prepubertal hypothyroidism suppresses both basal and stimulated Leydig cell activity in adult rats.
Abstract: Leydig cell steroidogenic activity under basal and stimulated conditions was studied in hypothyroid rats. Hypothyroidism was induced at a prepubertal age (30 days postpartum) by surgical thyroidectomy, and L-thyroxine (T4) supplementation (6 micrograms/100 g body weight/day for 30 days) to hypothyroid rats was begun after 30 days. Hypothyroidism for 60 days reduced serum LH and FSH without affecting prolactin. Serum and intratesticular testosterone and the specific activity of Leydig cell 3 beta- and 17 beta-hydroxysteroid dehydrogenases diminished in hypothyroid rats. The stimulatory effect of LH on Leydig cell steroidogenic activity and cAMP was also adversely affected in hypothyroid rats. All these changes were reversed by T4 supplementation. The present results suggest that prepubertal hypothyroidism suppresses both basal and stimulated Leydig cell activity in adult rats.
59 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...Hypothyroidism decreases testosterone and cAMP productions in rat testis under the response of LH by decreasing 3b-hydroxysteroid dehydrogenase (HSD) and 17b-HSD activities (Antony et al. 1995)....
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...Earlier Antony et al. (1995) reported that Leydig cell activity is suppressed in vivo and in vitro in hypothyroid rats....
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TL;DR: In vivo data strongly suggest that the thyroid hormone directly affects the development of prepuberal testes and the regulation of FSH-R and ABP gene expression in Sertoli cells, as well as the LH-R mRNA levels in Leydig cells, which may lead to further modulating the effect of gonadotropins on testes function.
Abstract: Thyroid hormone is known to play a pivotal role in the regulation of prepuberal rat testes development and function with specific influence on the differentiation of Sertoli cells, the only cell type that expresses thyroid hormone receptors in testes. To explore in vivo effects of thyroid hormone on testes development and the regulation of testicular gene expression, the hyper- and hypothyroid rat models were established by T3 injection to pups (ip 100 microg/kg bw) and by oral administration of 6-N-propyl-2-thiouracil (PTU) to the lactating mother from days 1 to 21 post-delivery. Half of the rats from each group were sacrificed at 21 days of age, and the other half were allowed to recover with discontinued treatments from day 22 to day 50. At 21 days of age, a significantly elevated serum T3 level was observed in hyperthyroid rats (179.5 ng/dl) vs controls (97.5 ng/dl), and in hypothyroid rats a significantly lower level of T3 was detected (26.1 ng/dl). However, serum T4 concentration was significantly lower in both hyper- (0.105 microg/dl) and hypothyroid (0.058 microg/dl) rats compared to the controls (2.48 microg/dl). In recovered rats in which the serum T3 and T4 were restored to normal, the serum T levels remained remarkably lower in both hyper- and hypothyroid rats. The significantly decreased body and testes weights observed in both hyper- and hypothyroid rats at 21 days of age were not restored by the time they were 50 days old. Histological analyses of testes of 21-day-old hypothyroid rats revealed smaller-sized seminiferous tubules, incomplete lumen formation and delayed germ cell differentiation and in hyperthyroid rats an increased number of early stage spermatocytes was found. Testicular mRNA levels of follicle-stimulating hormone receptor (FSH-R), luteinizing hormone receptor (LH-R) and androgen binding protein (ABP) were studied by Northern blot hybridization. At 21 days of age data showed that FSH-R mRNA levels were significantly higher in both hyper- and hypothyroid rat testes compared to controls, but no differences were detected in recovered 50-day-old rats. Significantly decreased ABP mRNA levels were detected only in hypothyroid rat testes compared to those in both the hyperthyroid and control groups at 21 days of age, but no significant change was observed in recovered 50-day-old rats. To further evaluate the effect of thyroid hormone on the Leydig cell function, the 2.3/2.6 kb specific LH-R hybridization bands were detected with rat LH-R cRNA probe. Significant suppression of LH-R mRNA levels was only observed in the hypothyroid rat testes at 50 days of age. The testicular thyroid hormone receptors (TRs) and the regulation of TR by thyroid hormone were investigated using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays. Both TRalpha and TRbeta mRNAs were identified in the testes from 21- and/or 50-day-old rats. TRalpha mRNA levels were significantly increased in hypothyroid rat testes and were suppressed in hyperthyroid rats at 21 days of age and no changes of TRalpha mRNA were found in recovered animals. Our in vivo data strongly suggest that the thyroid hormone directly affects the development of prepuberal testes and the regulation of FSH-R and ABP gene expression in Sertoli cells, as well as the LH-R mRNA levels in Leydig cells, which may lead to further modulating the effect of gonadotropins on testes function.
53 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...…Department of Zoology, University of Calcutta, 35, B. C. ROAD, Kolkata 700019, India 2018 Informa UK Limited, trading as Taylor & Francis Group follicle stimulating hormone receptor (FSH-R), and decrease of luteinising hormone receptor (LH-R) and androgen binding protein (Rao et al. 2003)....
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TL;DR: The present results indicate the expression of functional TSH receptors and D2 in human osteoblasts and suggest previously unrecognized roles of TSH receptor and local T(3) production by D2In the pathophysiology of human osteoblastasts.
Abstract: Thyroid hormones play important roles in bone growth, development, and turnover. To exert its biological activity, T(4) needs to be converted to T(3) by iodothyronine deiodinase. In human thyroid gland as well as rat brown adipose tissue, type 2 iodothyronine deiodinase (D2) expression is regulated by a TSH receptor-cAMP-mediated mechanism. TSH receptor knockout mice demonstrated the direct effects of TSH on bone via TSH receptors found on osteoblast and osteoclast precursors. In the present study we investigated the possible expression and function of iodothyronine deiodinase and TSH receptors in human osteoblast-like osteosarcoma (SaOS-2) cells and normal human osteoblast (NHOst) cells. Iodothyronine deiodinase activity was detected in SaOS-2 cells and NHOst cells, and all of the characteristics of deiodinating activity were compatible with those of D2. Northern analysis demonstrated D2 mRNA expression in SaOS-2 cells and NHOst cells. D2 mRNA levels as well as D2 activities were rapidly increased by dibutyryl cAMP or forskolin in SaOS-2 cells and NHOst cells. TSH receptor mRNA was demonstrated in SaOS-2 cells and NHOst cells, and D2 mRNA and D2 activity were stimulated by TSH in both cells. In addition, all T(3) receptor isoforms were detected by RT-PCR in SaOS-2 cells and NHOst cells. The present results indicate the expression of functional TSH receptors and D2 in human osteoblasts and suggest previously unrecognized roles of TSH receptors and local T(3) production by D2 in the pathophysiology of human osteoblasts.
53 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...PTU is known to act by inhibition of tetraiodothyronin5-deiodinase type I and type 2, of which type 2 is predominant in human osterblasts (Morimura et al. 2005)....
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...PTU is also effective even in very low dose (5mg/100gm body wt) and inhibited thyroxine-5 -deiodinase activity in rat kidney (Leonard and Rosenberg 1978) and in human osteoblast cells (Morimura et al. 2005)....
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