Caffeine and acetaminophen association: Effects on mitochondrial bioenergetics

Gonçalves, Débora Farina; Carvalho, Nélson Rodrigues de; Leite, Martim B.; Courtes, Aline Alves; Hartmann, Diane Duarte; Stefanello, Sílvio Terra; Silva, Ingrid K. da; Franco, Jeferson Luís; Soares, Félix Alexandre Antunes; Corte, Cristiane Lenz Dalla

doi:10.1016/j.lfs.2017.10.039

Cited by 23 publications

(11 citation statements)

References 45 publications

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“…Mitochondrial function can be affected by pesticide exposure, tobacco use or caffeine consumption. 10,22,23,44 We, among others, have reported that caffeinated soda intake was associated with earlier AAO 5 or increased PD risk. 45 Hence, caffeinated soda appears to be different from other caffeinated beverages and potentially caffeine-independent mechanisms are driving these effects.…”

Section: Discussionmentioning

confidence: 94%

“…For example, pesticide exposure can produce reactive oxygen species (ROS) by redox cycling, inducing mtDNA damage. 10 In addition, smoking and vaping have been shown to be associated with mitochondrial gene dysregulation 21 and there is evidence that caffeine affects mitochondrial bioenergetics 22 and increases mitochondrial function. 23 Our study aimed to analyze these interactions between the MGS and lifestyle and environment in LRRK2 -PD and iPD.…”

Section: Introductionmentioning

confidence: 99%

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Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism

Lueth

Gabbert

Koenig

et al. 2023

Preprint

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The objective of our study was to investigate the impact of the mitochondrial polygenic score (MGS) and lifestyle/environmental data on age at onset in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic Parkinson's disease (iPD). In this study, we included N=486 patients with LRRK2-PD and N=9259 patients with iPD from AMP-PD, Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data was utilized to perform the MGS analysis, using 14 Single Nucleotide Polymorphisms (SNPs) from genes causally associated with mitochondrial function and PD risk. Additionally, lifestyle and environmental data were obtained from the PD risk factor questionnaire (PD-RFQ). Correlation analyses and linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO. We observed that higher MGS was associated with earlier AAO in patients with LRRK2-PD (p=4.0x10-4, beta=-0.18) but not in patients with iPD. A correlation between MGS and AAO was visibly stronger in European ancestry LRRK2-PD patients (p=0.01, r=-0.16) than in Tunisian Arab-Berber patients (p=0.44, r=-0.05). We found that the MGS interacted with coffee (p=0.03, beta=-0.38) and caffeinated soda consumption (p=0.03, beta=-0.37) in LRRK2-PD and with caffeine soda consumption (p=0.047, beta=-0.22) and pesticide exposure (p=0.02, beta=-0.37) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeine or were exposed to pesticides. The MGS related to mitochondrial function was associated with AAO in LRRK2-PD but not iPD with an ethnic-specific effect. Caffeine consumption or pesticide exposure interacted with MGS to predict PD AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism

Lueth

Gabbert

Koenig

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Mitochondrial function can be affected by tobacco use, caffeine consumption, or pesticide exposure. 10,[21][22][23] We, among others, have reported that caffeinated soda intake was associated with earlier AAO 5 or increased PD risk. 47 Hence, caffeinated soda appears to be different from other caffeinated beverages and potentially caffeine-independent mechanisms are driving these effects.…”

Section: G S I S a S S O C I A T E D W I T Hmentioning

confidence: 91%

“…Mitochondrial function can be affected by tobacco use, caffeine consumption, or pesticide exposure. 10,[21][22][23] Smoking and vaping have been shown to be associated with mitochondrial gene dysregulation 24 and there is evidence that caffeine affects mitochondrial bioenergetics 22 and increases mitochondrial function. 23 Pesticides like rotenone or paraquat are known to increase mitochondrial dysfunction by inducing redox cycling or binding to complex I, which both result in the production of ROS.…”

mentioning

confidence: 99%

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism

et al. 2023

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BackgroundA mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk.ObjectiveTo investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2‐PD) and idiopathic PD (iPD).MethodsWe included N = 486 patients with LRRK2‐PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP‐PD), Fox Insight, and a Tunisian Arab‐Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD‐RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO.ResultsOur derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10−8). We observed that higher MGS was significantly associated with earlier AAO in LRRK2‐PD (P = 0.047, β = −1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2‐PD patients of European descent (P = 0.049, r = −0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = −0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = −5.65) in LRRK2‐PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non‐smokers.ConclusionsThe MGS was more strongly associated with earlier AAO in LRRK2‐PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene–environment interactions as modifiers of AAO in LRRK2‐PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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“…While scarce, a few studies have examined the role of components which could influence hepatotoxicity of some of these drugs. Caffeine has been shown to influence APAP-induced liver injury by improving mitochondrial function [193], though it was given 30 minutes prior to APAP treatment, and hence it is unclear if influence on APAP metabolism played a role in the observed protection. Early studies on acute ethanol administration before APAP overdose showed a preventive effect of ethanol on APAP-induced hepatotoxicity due to interference with APAP metabolism [194], though additional mechanisms influencing mitochondrial transport of NADPH are also suggested [195].…”

Section: Additional Factors Influencing Effects Of Drugs On Mitochmentioning

confidence: 99%

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

et al. 2018

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Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area.

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Caffeine and acetaminophen association: Effects on mitochondrial bioenergetics

Abstract: We suggest that the antioxidant effects of caffeine and/or its interactions with mitochondrial bioenergetics may be involved in its beneficial effects against APAP hepatotoxicity.

Cited by 23 publications

References 45 publications

Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism

Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

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