Abstract
Background: Peripheral neuropathy is the dose-limiting toxicity of stavudine and didanosine (nucleoside analogs used in HIV treatment) and is attributed to mitochondrial toxicity from these drugs. Acetyl L-carnitine (ALC) and co-enzyme Q10 are proposed as neuropathy treatments, but evidence to support these is limited. Methods: We examined ALC and a water-soluble formulation of co-enzyme Q10 (HQO™) for the prevention of d4T and ddI neurotoxicity using cultured fetal rat DRG as an in vitro model. Results: DdI (33μM) and d4T (50μM) caused clear toxicity (impaired neurite growth) by day 8 of DRG culture. HQO™ at concentrations 1-100μM completely prevented the toxicity of 33μM ddI in vitro and ALC at concentrations 1-100 μM substantially (but incompletely) prevented ddI toxicity in this model. In contrast, ALC was ineffective at all concentrations tested for preventing the toxicity of 50μM d4T. HQO™ showed dose-dependent efficacy for preventing d4T toxicity. HQO™ (1μM) partially prevented d4T toxicity while 10 and 100μM HQO™ completely prevented d4T toxicity in this model. Conclusions: We find HQO™ is superior to ALC for preventing the neurotoxicity of d4T (the HIV treatment most associated with neuropathy) and ddI in vitro. Further study is needed to clarify any clinical role for co-enzyme Q10 coadministration with d4T and ddI and to assess whether this compound may have a role in treating established cases of neuropathy.
Keywords: HIV, stavudine, neuropathy, coenzyme Q10, acetyl L-carnitine
Current HIV Research
Title: Ubisol-AquaTM: Coenzyme Q10 Prevents Antiretroviral Toxic Neuropathy in an In Vitro Model
Volume: 8 Issue: 3
Author(s): Catherine L. Cherry, Masqura Mobarok, Steven L. Wesselingh, Randi Fain, Shelley Weinstock, Gilda Tachedjian, Seema Srivastava, David P. Tyssen, Jonathan D. Glass and David J. Hooker
Affiliation:
Keywords: HIV, stavudine, neuropathy, coenzyme Q10, acetyl L-carnitine
Abstract: Background: Peripheral neuropathy is the dose-limiting toxicity of stavudine and didanosine (nucleoside analogs used in HIV treatment) and is attributed to mitochondrial toxicity from these drugs. Acetyl L-carnitine (ALC) and co-enzyme Q10 are proposed as neuropathy treatments, but evidence to support these is limited. Methods: We examined ALC and a water-soluble formulation of co-enzyme Q10 (HQO™) for the prevention of d4T and ddI neurotoxicity using cultured fetal rat DRG as an in vitro model. Results: DdI (33μM) and d4T (50μM) caused clear toxicity (impaired neurite growth) by day 8 of DRG culture. HQO™ at concentrations 1-100μM completely prevented the toxicity of 33μM ddI in vitro and ALC at concentrations 1-100 μM substantially (but incompletely) prevented ddI toxicity in this model. In contrast, ALC was ineffective at all concentrations tested for preventing the toxicity of 50μM d4T. HQO™ showed dose-dependent efficacy for preventing d4T toxicity. HQO™ (1μM) partially prevented d4T toxicity while 10 and 100μM HQO™ completely prevented d4T toxicity in this model. Conclusions: We find HQO™ is superior to ALC for preventing the neurotoxicity of d4T (the HIV treatment most associated with neuropathy) and ddI in vitro. Further study is needed to clarify any clinical role for co-enzyme Q10 coadministration with d4T and ddI and to assess whether this compound may have a role in treating established cases of neuropathy.
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Cherry Catherine L., Mobarok Masqura, Wesselingh Steven L., Fain Randi, Weinstock Shelley, Tachedjian Gilda, Srivastava Seema, Tyssen David P., Glass Jonathan D. and Hooker David J., Ubisol-AquaTM: Coenzyme Q10 Prevents Antiretroviral Toxic Neuropathy in an In Vitro Model, Current HIV Research 2010; 8 (3) . https://dx.doi.org/10.2174/157016210791111106
DOI https://dx.doi.org/10.2174/157016210791111106 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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