Physiological processes underlying organ injury in alcohol abuse

Souza‐Smith, Flavia M.; Lang, Charles H.; Nagy, Laura E.; Bailey, Shannon M.; Parsons, Loren H.; Murray, Gary J.

doi:10.1152/ajpendo.00270.2016

Cited by 25 publications

(25 citation statements)

References 94 publications

(128 reference statements)

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“…In keeping with this notion, preliminary studies suggested diminished ethanol-induced anxiety in inhibitor-treated mice compared with untreated animals as evaluated by the open field test (Hsu and Haj, data not shown). Systemic delivery of PTP1B inhibitor may be of value as alcohol can permeate a plethora of tissues with adverse consequences [ 71 ]. Indeed, PTP1B inhibition using antisense oligonucleotides enhances insulin sensitivity and decreases weight in T2D patients [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatic protein-tyrosine phosphatase 1B disruption and pharmacological inhibition attenuate ethanol-induced oxidative stress and ameliorate alcoholic liver disease in mice

et al. 2020

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Alcoholic liver disease (ALD) is a major health problem and a significant cause of liver-related death. Currently, the mainstay for ALD therapy is alcohol abstinence highlighting the need to develop pharmacotherapeutic approaches. Protein-tyrosine phosphatase 1B (PTP1B) is an established regulator of hepatic functions, but its role in ALD is mostly unexplored. In this study, we used mice with liver-specific PTP1B disruption as well as pharmacological inhibition to investigate the in vivo function of this phosphatase in ALD. We report upregulation of hepatic PTP1B in the chronic plus binge mouse model and, importantly, in liver biopsies of alcoholic hepatitis patients. Also, mice with hepatic PTP1B disruption attenuated ethanol-induced injury, inflammation, and steatosis compared with ethanol-fed control animals. Moreover, PTP1B deficiency was associated with decreased ethanol-induced oxidative stress in vivo and ex vivo . Further, pharmacological modulation of oxidative balance in hepatocytes identified diminished oxidative stress as a contributor to the salutary effects of PTP1B deficiency. Notably, PTP1B pharmacological inhibition elicited beneficial effects and mitigated hepatic injury, inflammation, and steatosis caused by ethanol feeding. In summary, these findings causally link hepatic PTP1B and ALD and define a potential therapeutic target for the management of this disease.

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Section: Discussionmentioning

confidence: 99%

Hepatic protein-tyrosine phosphatase 1B disruption and pharmacological inhibition attenuate ethanol-induced oxidative stress and ameliorate alcoholic liver disease in mice

et al. 2020

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“…No Brasil, o consumo de bebidas alcoólicas é observado em 50% da população adulta [51]. O seu uso é associado à presença de modificações fisiológicas consideráveis e pode gerar efeitos prejudiciais em diferentes sistemas no organismo [52]. Estudos demonstram que a ingestão de álcool em concentrações de 4%, 10% e 40% (v/v) é responsável pelo retardo do esvaziamento gástrico e da redução da motilidade intestinal [53,54].…”

Section: Alcoolismounclassified

“…Estudos demonstram que a ingestão de álcool em concentrações de 4%, 10% e 40% (v/v) é responsável pelo retardo do esvaziamento gástrico e da redução da motilidade intestinal [53,54]. O seu consumo é capaz também de gerar lesões nas células hepáticas e alterar as enzimas metabólicas presentes no fígado [52].…”

Section: Alcoolismounclassified

Alterações farmacocinéticas de antimicrobianos em situações especiais: uma revisão narrativa

Sousa¹,

Frade²,

Vieira³

et al. 2019

Rev. Ciênc. Méd.

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Até o ano de 1940, as doenças infecciosas eram uma das principais causas de morte no Brasil. Atualmente, apesar de um grande declínio, a mortalidade ainda é elevada em relação a países desenvolvidos e a outros países da América Latina. Dessa maneira, o objetivo do presente trabalho foi relatar as alterações fi siológicas em condições específi cas, as consequências na farmacocinética dos antimicrobianos e ainda o impacto do ajuste de dose em tais situações. Realizou-se uma revisão narrativa de artigos publicados sobre a utilização de antimicrobianos nas seguintes situações: doença crítica e sepse, alcoolismo, tabagismo, extremos de idade, obesidade, nutrientes, polimorfismo genético, gravidez e lactação, insuficiência cardíaca, insuficiência hepática e renal. Observou-se que as alterações fisiológicas em tais situações afetam a farmacocinética dos antimicrobianos, modificando os processos de absorção, distribuição, metabolismo e excreção, os quais dependem muitas vezes da natureza do fármaco, podendo requerer ajuste de dose. Pôde-se concluir que as alterações observadas reduzem a precisão de uma dose terapêutica eficaz, evidenciando, dessa maneira, a importância do ajuste de dose.

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“…Alcohol use disorder is a major health issue with enormous socioeconomic costs. The detrimental effects of acute and chronic alcohol consumption on liver, pancreas, and brain are well documented 1 . Chronic alcohol consumption also causes the loss of skeletal muscle strength and cardiac contractile function 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Sheoran

Richmond

et al. 2020

FASEB j.

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Chronic excessive ethanol consumption has distinct toxic and adverse effects on a variety of tissues. In skeletal muscle, ethanol causes alcoholic myopathy, which is characterized by myofiber atrophy and the loss of muscle strength. Alcoholic myopathy is more prevalent than all inherited muscle diseases combined. Current evidence indicates that ethanol directly impairs muscle organization and function. However, the underlying mechanism by which ethanol causes toxicity in muscle is poorly understood. Here, we show that the nematode Caenorhabditis elegans exhibits the key features of alcoholic myopathy when exposed to ethanol. As in mammals, ethanol exposure impairs muscle strength and induces the expression of protective genes, including oxidative stress response genes. In addition, ethanol exposure causes the fragmentation of mitochondrial networks aligned with myofibril lattices. This ethanol‐induced mitochondrial fragmentation is dependent on the mitochondrial fission factor DRP‐1 (dynamin‐related protein 1) and its receptor proteins on the outer mitochondrial membrane. Our data indicate that this fragmentation contributes to the activation of the mitochondrial unfolded protein response (UPR). We also found that robust, perpetual mitochondrial UPR activation effectively reduces muscle weakness caused by ethanol exposure. Our results strongly suggest that the modulation of mitochondrial stress responses may provide a method to ameliorate alcohol toxicity and damage to muscle.

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Physiological processes underlying organ injury in alcohol abuse

Cited by 25 publications

References 94 publications

Hepatic protein-tyrosine phosphatase 1B disruption and pharmacological inhibition attenuate ethanol-induced oxidative stress and ameliorate alcoholic liver disease in mice

Hepatic protein-tyrosine phosphatase 1B disruption and pharmacological inhibition attenuate ethanol-induced oxidative stress and ameliorate alcoholic liver disease in mice

Alterações farmacocinéticas de antimicrobianos em situações especiais: uma revisão narrativa

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

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