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: The results demonstrate that the time of administration of melatonin within the day-night cycle is critical for melatonin action.
Abstract: Immature male Wistar rats with a 12:12 h light-dark cycle received daily s.c. melatonin injections of 100 micrograms from 20 to 40 days of age. Melatonin administration during the late photophase (9 h after the onset of light) or during the late scotophase (9 h after the onset of darkness) caused reduced weights of testes and seminal vesicles, lowered plasma levels of testosterone, LH and FSH, and decreased number of pituitary GnRH receptors, a series of observations which reflects delayed sexual maturation at 40 days. In contrast, no effect was observed when melatonin was injected during the early photophase of scotophase (5 h after the onset of light or darkness, respectively). In order to better investigate the night hours, melatonin action was studied in rats that were born and raised with a shifted 12:12 h light-dark cycle. When the light phase was shifted by 5 and 17 h 1 week before the animals were born, sensitivity to melatonin action was unchanged. The responsiveness of the neuroendocrine-reproductive axis to exogenous melatonin was then studied throughout the day-night cycle. The inhibitory influence of melatonin increased gradually during the late photophase and reached a peak just before the onset of darkness. No effect was observed during the first 7 h of the dark phase; however, melatonin injected 9 h after the onset of darkness again had an inhibitory influence equivalent to about 50% of that observed in the late photophase , whereas administration 2 h later remained without effect. These results demonstrate that the time of administration of melatonin within the day-night cycle is critical for melatonin action.(ABSTRACT TRUNCATED AT 250 WORDS)
53 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...Melatonin injection, 9 h after the onset of light or darkness caused testis and accessories dysfunction with lowered plasma testosterone, LH, FSH and decreased number of pituitary GnRH receptors, reflecting delayed sexual maturation at 40 days (Lang et al. 1984)....
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TL;DR: Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells, and should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays.
51 citations
"Arecoline inhibits pineal-testis fu..." refers methods in this paper
...On addition of the chromogen, TMB, a colour was developed only in those wells in which the enzyme conjugate was present, indicating the presence of TSH....
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...Additionally T4 and TSH levels were further altered after joint treatment of PTU and arecoline (Figure 1(b,c))....
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...Since T4 and TSH productions were partially altered, unlike T3, there is an indication of synergism at least in T4 and TSH productions in arecoline and PTU treated rats....
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...Test sera were added into the wells and goat anti-TSH conjugated with horse-radish peroxidase was added....
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...Serum TSH (Soos and Siddle 1982), total triiodothyronine (T3) (Walker 1977) and total thyroxine (T4) (Schuurs and Van Weeman 1977) levels were quantitated by EIA kit (Pathozyme-TSH, T3 and T4) of OMEGA, UK....
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TL;DR: Results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland, possibly mediated by excess CRH.
Abstract: The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouraciltreated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH.
50 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...…hyperactivity may also contribute to the inhibition of luteinizing hormone releasing hormone (LHRH) secretion from the hypothalamus, mediated via excess secretion of corticotropin-releasing hormone (CRH), which in turn probably suppressed testicular activity in PTU-treated rats (Tohei et al. 1997)....
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TL;DR: It is observed isolated hepatotoxicity in two children treated with propylthiouracil (PTU) for hyperthyroidism, and one of them died and the drug was promptly discontinued when signs of liver disease were noted.
Abstract: We have observed isolated hepatotoxicity in two children treated with propylthiouracil (PTU) for hyperthyroidism. Neither patient had risk factors for or clinical evidence of preexisting liver disease. In one patient the drug was promptly discontinued when signs of liver disease were noted. This patient quickly recovered. The second patient continued to receive PTU for several days after developing symptoms. Her illness progressed to fulminant hepatic failure with encephalopathy, and she died. These are the third and fourth pediatric cases reported, and there have been 10 cases reported in adults in the English language literature. Thirteen of the 14 patients are female. The literature regarding all these patients is reviewed. Propylthiouracil may cause lethal hepatic damage. This drug should be discontinued immediately if signs or symptoms of hepatic injury are detected.
42 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...Thyroid hormones and StAR proteins are directly correlated to regulate steroid hormone biosynthesis by the Leydig cells (Jonas and Eidson 1988, Manna et al. 2001)....
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Journal Article•
TL;DR: The results suggest that melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary axis and there is a functional relationship and feedback regulation between the pineal gland and the testes.
Abstract: OBJECTIVES: We have investigated the changes in serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone levels together with testicular histology in both pinealectomized (PNX) and intact rats. MATERIAL and METHODS: Twenty-one animals were PNX and allowed to recover for two months. Group I was assigned as PNX, group II PNX+melatonin and group III PNX+Human Chorionic Gonadotropin (HCG). Rats in group IV were sham PNX (S-PNX). An intact group of animals was s.c. injected with melatonin (0.5 mg/kg/day), another group with a combination of melatonin+HCG (5000 IU/kg/day) for seven days. Controls received saline alone (1 ml/kg). At the end, all animals were decapitated and blood samples obtained. Serum LH and FSH levels were determined by Radioimmunoassay, testosterone values by Chemiluminescent Enzyme Immunassay. Testicular tissue was collected and processed for light microscopy. RESULTS: Serum LH levels were increased following PNX, but no such increases were seen in testosterone. In the PNX+melatonin group, serum LH and testosterone values were found to be similar to those of S-PNX group. HCG supplementation to PNX rats resulted in significant decreases in LH (p<0.005), but increased testosterone levels (p<0.001). Melatonin administration to intact animals significantly decreased both LH and testosterone levels (p<0.01). Co-administration of HCG+melatonin resulted in significant decreases in LH (p<0.001) and increases in testosterone levels (p<0.01). Serum FSH values did not show significant changes among groups. Only HCG administration significantly reduced FSH levels (p<0.01). CONCLUSIONS: Our results suggest that melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary axis. There is a functional relationship and feedback regulation between the pineal gland and the testes.
36 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...There are other evidences that melatonin inhibits testosterone production suggesting anti-gonadal relationship of the pineal gland (Kus et al. 2000, Yilmaz et al. 2000, Saha et al. 2007), but this interrelationship is probably abolished at least in our experimentally-induced hypothyroid rats,…...
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