Distribution and accumulation of caffeine in rat tissues and its inhibition on semicarbazide-sensitive amine oxidase

Che, Baoquan; Wang, Lin; Zhang, Zhe; Zhang, Yongqiang; Deng, Yulin

doi:10.1016/j.neuro.2012.07.004

Cited by 21 publications

(22 citation statements)

References 31 publications

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“…However, it is clear that when administered as drugs, the resulting amounts of some methylxanthines could inhibit this enzyme. The only in vivo study reported to date showed that caffeine, when administered to rats, inhibited PrAO in adipose tissues [62]. Our study clearly supports a similar observation for humans.…”

Section: Discussionsupporting

confidence: 89%

“…This can only be determined by more detailed in vivo studies with human volunteers. The only in vivo study reported to date was carried out in rats [62]. That study reported that "caffeine was found to be present in all tissues after administration for 10 days and accumulated for 25 days" and that rising caffeine levels correlated with loss of PrAO activity.…”

Section: Discussionmentioning

confidence: 99%

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Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

et al. 2020

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Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

et al. 2020

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“…Previous studies in these laboratories explored the inhibition of PrAO by amine compounds in food and drugs and showed that caffeine inhibited bovine PrAO with a Ki of 1.0 mM (Olivieri & Tipton, ; Olivieri et al, ). A subsequent study (Che, Wang, Zhang, Zhang, & Deng, ) showed that caffeine administration to rats inhibited PrAO activity in serum, brain, and adipose tissue and raised the possibility that caffeine could be used in treating PrAO‐associated disease. Trials assessing the impact of caffeine on PrAO activity in human subjects have been considered but have not yet been initiated (see https://clinicaltrials.gov/ct2/show/NCT02098785).…”

Section: Introductionmentioning

confidence: 99%

Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase

Shanahan¹,

O'Sullivan

Tipton

et al. 2018

J Food Biochem

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Methylxanthines are among the most widely consumed drugs in the world and evidence of their health benefits has been growing in recent years. Primary Amine Oxidase (PrAO) has been recognized as a therapeutic target for the amelioration of inflammatory, vascular, and neurodegenerative diseases. Previous work in our laboratories showed that caffeine inhibited Bovine PrAO with a Ki of 1.0 mM using benzylamine as substrate. This study aimed to extend our previous work and explore the possibility that related methylxanthines might influence PrAO activity. While paraxanthine, theophylline, and 7‐methylxanthine had little effect on PrAO, theobromine was a noncompetitive inhibitor with a Ki of 276 ± 44 µM. The specific structural elements of methylxanthines that are required for inhibition allow us to suggest that their binding site on PrAO may be a target for therapeutics. The health benefits associated with dietary methylxanthine consumption could involve PrAO inhibition. Practical applications Inhibition of PrAO by methylxanthines may be significant in conferring health benefits. The design of PrAO inhibitors based on the structural motifs identified in this study (N‐methylation at specific locations) is indicated. Existing therapeutics based on a core xanthine structure can be evaluated for their effects on PrAO. PrAO inhibition must be considered as a potential mediator of the beneficial health effects of some methylxanthines. If inhibition in human tissues is comparable to, or greater than, that found in these studies it points to an important role for these compounds in human health.

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“…Concomitantly, it is pivotal that coffee/caffeine consumption has been demonstrated to be able to reduce hepatic fibrosis in NASH patients significantly [76]. In different tissues, SSAO activity was diversely diminished after 10 days of caffeine administration, e.g., in the adipose tissue it was diminished by 41.4%, which was the highest amount compared to the rest of the samples (aorta, liver, kidney, serum) [13]. Green tea-caffeine mixture intake ameliorates weight maintenance and weight loss Westerterp-Plantenga et al [10] In a view of the fact that caffeine toxicity is low [83], it might be considered as a promising SSAO inhibitor which might aid the drug development in medicine against SSAO-mediated health disorders.…”

Section: Dual Beneficial Role Of Caffeine For Obese Peoplementioning

confidence: 99%

“…However, these researches focus on the ability of caffeine to boost metabolism and increase energy expenditure [11,12]. In this manuscript, we review another beneficial role of caffeine for overweight subjects, which is the potential to inhibit enzymatic activity of SSAO [13]. Histamine-a naturally occurring bioamine in body and food-merits attention since the activity of this compound is associated with SSAO metabolism and lipolysis in adipose tissue [14].…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Weight Gain and Prevention of Associated Pathologies by Inhibiting SSAO

2020

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Obesity is a worldwide prevalent metabolic disorder that is associated with diabetes, among many other diseases. Bearing this in mind, prevention and treatment ways need to be improved. Notably, activity of the enzyme semicarbazide-sensitive amine oxidase (SSAO) is found to be elevated in overweight subjects. Moreover, SSAO inhibition has resulted in an increase of histamine activity in adipose tissue and the limitation of body fat. The current review aims to overview the risks of obesity, rationalize the molecular ways of SSAO activity, and outline the strategies of inhibiting upregulated enzyme levels. It describes the differences between SSAO inhibitors and advances the prospective agents. Based on evidence, caffeine is proposed as an effective, safe, and reliable choice to inhibit SSAO activity. Furthermore, the histamine in adipocytes has been associated with SSAO activity. Therefore, it is suggested as one of the key compounds to be studied for obesity management. To conclude, inhibiting SSAO may attenuate weight gain and prevent related diseases.

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Distribution and accumulation of caffeine in rat tissues and its inhibition on semicarbazide-sensitive amine oxidase

Cited by 21 publications

References 31 publications

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase

Attenuation of Weight Gain and Prevention of Associated Pathologies by Inhibiting SSAO

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