[PMID]: | 29293553 |
[Au] Autor: | Persons AL; Bradaric BD; Dodiya HB; Ohene-Nyako M; Forsyth CB; Keshavarzian A; Shaikh M; Napier TC |
[Ad] Endereço: | Department of Psychiatry, Rush University Medical Center, Chicago, IL, United States of America. |
[Ti] Título: | Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats. |
[So] Source: | PLoS One;13(1):e0190078, 2018. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults. |
[Mh] Termos MeSH primário: |
Colo/fisiopatologia Infecções por HIV/fisiopatologia HIV-1/genética Metanfetamina/administração & dosagem
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[Mh] Termos MeSH secundário: |
Animais Genótipo Infecções por HIV/complicações Mucosa Intestinal/fisiopatologia Masculino Ratos Ratos Endogâmicos F344 Ratos Transgênicos Autoadministração
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 44RAL3456C (Methamphetamine) |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180206 |
[Lr] Data última revisão:
| 180206 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180103 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0190078 |
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