2013
DOI: 10.2131/jts.38.741
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Differential responses of human hepatocytes to the non-nucleoside HIV-1 reverse transcriptase inhibitor nevirapine

Abstract: -Nevirapine is a non-nucleoside reverse transcriptase (RT) inhibitor used for the treatment of AIDS and the prevention of mother-to-child transmission of HIV-1. Despite its therapeutic ben--ity. The present study examined the effects of nevirapine on cell growth and death in human hepatocyte HepG2 cells and THLE2 cells and the possible pathways involved in these effects. The concentrations of nevirapine inhibiting 50% cell growth were similar for both cell lines. Nevirapine (0-250 μM) treatment caused a slight… Show more

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Cited by 12 publications
(13 citation statements)
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“…In a previous study we determined that the IC 50 of NVP in HepG2 cells was approximately 819 μM 13 , somewhat lower than the value determined by others 16 . Long term culture of cells with 819 μM NVP results in caspase 9 mediated cell death by week 3 of culture 13 .…”
Section: Resultsmentioning
confidence: 56%
“…In a previous study we determined that the IC 50 of NVP in HepG2 cells was approximately 819 μM 13 , somewhat lower than the value determined by others 16 . Long term culture of cells with 819 μM NVP results in caspase 9 mediated cell death by week 3 of culture 13 .…”
Section: Resultsmentioning
confidence: 56%
“…The lower of the two concentrations chosen approximated the plasma threshold for clinical efficacy, and the higher dose was a low multiple of the C max . These were significantly below those which many culture systems typically use in their toxicity assessments(18). Fang and Beland(18) estimated an IC 50 of 813.7 μM for a 48 hour of Nevirapine which was almost six times the higher toxic concentration used in our study.…”
Section: Discussionmentioning
confidence: 79%
“…These were significantly below those which many culture systems typically use in their toxicity assessments(18). Fang and Beland(18) estimated an IC 50 of 813.7 μM for a 48 hour of Nevirapine which was almost six times the higher toxic concentration used in our study. Such high concentrations are useful for cytotoxicity metrics but may not reveal subtler pathway perturbations reflective of early mechanisms.…”
Section: Discussionmentioning
confidence: 79%
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“…HeLa cells treated with nevirapine underwent premature senescence that was associated with activation of the DNA damage response (Stefanidis et al, 2008). Nevirapine appears to have differential senescence induction capabilities because while it was able induce a growth arrest in both HepG2 cells and THLE2, an immortalized human liver cell line, senescence markers were only present in THLE2 cells (Fang and Beland, 2013). The relevance of these results towards HIV co-morbidities is uncertain because of the use of immortalized cell lines but to date no study has examined NNRTI senescence in primary cells.…”
Section: Haart Drug Induced Senescencementioning
confidence: 99%