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.
Citations
More filters
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]....
[...]
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
More filters
TL;DR: It is concluded that the prepubertal pineal gland has a higher melatonin secretion rate than the adult gland and the inconsistent ratio between serum and salivary melatonin calls for caution in the use of salivARY melatonin for pharmacokinetic studies or to infer pineal function.
Abstract: To determine whether melatonin pharmacokinetics change during puberty, we infused melatonin iv in 9 prepubertal, 8 pubertal, and 16 adult subjects and measured melatonin in serum and saliva, and 6-hydroxymelatonin sulfate in urine. A pilot study of 3 adult males showed dose linearity, absence of saturation kinetics, and unaltered metabolism and urinary excretion for doses of 0.1, 0.5, and 5.0 micrograms/kg. All other subjects received 0.5 microgram/kg melatonin. The results of pharmacokinetic parameters calculated from serum melatonin showed no significant gender differences in adults. However, developmental differences were significant between prepubertal children and adults for terminal elimination rate constant (1.08 +/- 0.25 vs. 0.89 +/- 0.11 h-1), elimination half-life (0.67 +/- 0.12 vs. 0.79 +/- 0.10 h), and area under the concentration-time curve (250.9 +/- 91.8 vs. 376.9 +/- 154.3 (pg/mL).h, respectively). At all time points melatonin levels were higher in serum than in saliva, and the ratio betwe...
81 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...Melatonin (N-acetyl-5-methoxy tryptamine) has functional regulation of reproductive axis in various animals, as reported, suppression of reproductive axis (Cavallo and Ritschel 1996)....
[...]
...Cavallo and Ritschel (1996) demonstrated higher melatonin secretion in prepubertal pineal in humans....
[...]
...Since pineal is known to be higher in prepubertal human, ewes and fish than in adults (Cavallo and Ritschel 1996), its relationship in hypothyroid rat is not reflected which remains to be known in rats....
[...]
TL;DR: Data indicate a close inverse relationship between PTU dose and both thyroid hormone biosynthesis and peripheral T4 deiodination, and short and long term PTU treatments have quantitatively similar effects on thyroid function, although recovery of thyroid function is prolonged after long term treatment.
Abstract: Using a sensitive and specific RIA for propylthiouracil (PTU), we examined the effects of short term (1 week) and long term (1 month) PTU treatment on thyroid function in the rat, and correlated changes in thyroid function with serum and thyroid PTU levels. After 1 week, dose-dependent decreases in thyroid PBI, serum T4, and serum T3 were observed, with concomitant elevations in the serum rT3 to T4 ratio and serum TSH. Fifty percent suppression of thyroid PBI occurred at a PTU concentration in the drinking water of 0.0005% (ED50), with concomitant serum and thyroid PTU levels of 0.3 micrograms/ml and 300 ng/thyroid, respectively. After 1 month of PTU, serum T4 values were lower than after 1 week of treatment for all PTU concentrations, but values for the other thyroid functional variables were similar to those in the 1 week group at comparable PTU dosage. The PTU dose-response curve for thyroid PBI was similar to that seen after 1 week of treatment, with an ED50 of 0.0004%. After discontinuation of PTU treatment, PTU disappeared from serum in a biexponential fashion, with an early rapid distribution phase (t 1/2 = approximately 4 h) and a second slower elimination phase (t 1/2 = approximately 2.6 days). In the thyroid, an initial increase in PTU content was seen up to 18 h after PTU withdrawal; thereafter, thyroid PTU declined linearly, with a t 1/2 of 1.4 days in both groups. After PTU withdrawal, thyroid PBI recovered with a t 1/2 of 1.09 days after 1 week on PTU, but recovery was prolonged (t 1/2 = 2.8 days) after 1 month of treatment. Log thyroid PTU and log thyroid PBI were linearly related after PTU withdrawal (r = 0.97; P less than 0.001) after 1 week but not after 1 month. Serum T4 and serum T3 remained below control values for 2 days, but then rapidly normalized, with T3 values rising transiently above the control value. This rebound occurred at a time when PTU was still present within the thyroid, before thyroid PBI had returned to baseline. These data indicate a close inverse relationship between PTU dose and both thyroid hormone biosynthesis and peripheral T4 deiodination. In addition, short and long term PTU treatments have quantitatively similar effects on thyroid function, although recovery of thyroid function is prolonged after long term treatment. The biexponential disappearance of PTU from the serum is compatible with a two-compartment model of PTU distribution. The early increase in thyroid PTU after drug withdrawal is suggestive of an inhibitory effect of PTU upon its own uptake by the thyroid, whereas the faster disappearance of PTU from the thyroid than from serum is consistent with intrathyroid drug metabolism.
79 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...In rats, serum PTU levels of 0.3 mg/ml and 300 ng/thyroid significantly reduced thyroid protein bound iodine (PBI) and serum T3 and T4 levels (Cooper et al. 1983)....
[...]
TL;DR: It is concluded that arecoline attacks multiple targets to finally generate systemic toxicity in mice and caused depression of antioxidants, i.e., superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutATHione-S-transferase (GST) that are known to neutralize reactive oxygen species.
75 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...It has several adverse side effects, like increased risk of oral cancer in humans (IARC 2004), immunosuppression, hepatotoxicity and impaired antioxidant production in mice (Dasgupta et al. 2006)....
[...]
...Arecoline intake by chewing betel nut has diverse untoward side effects as reported earlier (Dasgupta et al. 2006)....
[...]
73 citations
TL;DR: Arecoline, a cholinergic agonist, administered at low doses by continuous intravenous infusion for up to 2 weeks, significantly and replicably improved memory in five of nine subjects with mild-moderate Alzheimer's disease.
Abstract: Arecoline, a cholinergic agonist, administered at low doses by continuous intravenous infusion for up to 2 weeks, significantly and replicably improved memory in five of nine subjects with mild-moderate Alzheimer's disease. During dose finding, performance on a verbal memory task improved with an inverted U-shaped relation to dose. Six of nine subjects were classified as responders. During blinded, placebo-controlled, individualized optimal dosing for 5 days, verbal memory again improved in five of six responders but not in any non-responder. No adverse drug effects occurred. Arecoline, and possibly other cholinergic agonists, can safely improve memory in Alzheimer's disease at doses much lower than previously studied.
72 citations
"Arecoline inhibits pineal-testis fu..." refers background in this paper
...The nut contains arecoline, as principal alkaloid, which has therapeutic value for the treatment of Alzheimer with presenile dementia (memory enhancer) (Soncrant et al. 1993) and Schizophrenia (Sullivan et al. 2000)....
[...]