Uridine treatment for mitochondrial toxicity
1 September 2003. Related: Conference reports, Side effects, Lipodystrophy and metabolic complications, Lipodystrophy Workshop (IWADRW) 5th Paris 2003.
Simon Collins, HIV i-Base
A possible treatment for nucleoside-related mitochondrial toxicity was suggested by Ulrich Walker form University of Freiburg. [24]
Human hepatocytes were exposed to NRTIs with or without uridine for 25 days. Severe depletion of mtDNA, reduction in cell proliferation and increase in lactate and steatosis developed with exposure to ddC and d4T (but not ddI) which was largely reversed in the presence of uridine. It also reversed cell toxicity and lactate of AZT and 3TC-exposed cells.
Interactions with nucleoside were not found and uridine did not affect RTI IC50 or IC90 of any of the nucleosides in resistance assays.
In humans, serum levels of uridine achieved protective levels in the in vitro model following a single 36g dose of a dietary supplement Mitocnol and studies of uridine therapy in HIV-positive patients are now underway. (A website with details if Uridine is at http://www.nucleomaxX.com – see also more detained article below in IAS report).
This article is part of a longer report from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy, 8-11 July 2003, Paris. Part ten of this report.
Reference:
Unless otherwise stated, all abstracts refer to the programme and abstracts from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 8-11 July 2003, Paris and are published in Antiviral Therapy Volume 8 issue 4.
- Walker U, Koch E, Venhoff N et al – Uridine prevents and treats mtDNA depletion by NRTI pyrimidine analogues and fully restores mitochondrial function. Abstract 19.