Mildronate's protective effects in the peripheral nervous system : Stavudine-induced neuropathy and formalin-induced inflammation

Funding Information: This work was supported by the Latvian Council of Science Grant Nr. 05-1418; ESF Grant ESS2004/3; Contract No. 453, between the Latvian Institute of Organic Synthesis and the Joint Stock Company “Grindex”; Contract No. 2377, between the University of Latvia and the Joint Stock Company “Grindex”; and a L’ORÉAL Latvian “For Women In Science” fellowship with the support of the Latvian National Commission for UNESCO and the Latvian Academy of Sciences.Mildronate, previously known as a cardioprotective drug, recently was found to normalise mitochondrial processes by preventing the dysfunction of complex I in rat liver mitochondria. Previously we have shown also the ability of mildronate to prevent pathologies in the central nervous system by normalizing the expression of different signalling molecules in brain tissue. This allowed us to suggest that mildronate may possess a beneficial role also in peripheral nervous system pathologies. The present study was designed to assess the peripheral tissue damage caused by anti-HIV drug stavudine, as well as pain and inflammation caused by formalin. For this demonstration, we investigated the influence of mildronate: (1) on decreased myelin expression and increased neuron degeneration in rat sciatic nerve tissue caused by stavudine; and (2) on formalin-induced inflammation in mice. We found that mildronate protected the stavudine-induced degeneration of neurons in rat peripheral sciatic nerve without a significant influence on demyelination. In a formalin test, mildronate showed anti-inflammatory action comparable to that of indomethacin, a reference drug. The present results show that mildronate is capable of regulating peripheral nerve damage and peripheral inflammatory responses. We suggest that the multifunctional effects of mildronate can be attributed to its ability to regulate mitochondrial processes. The obtained data indicate protective effects of mildronate in different peripheral neurological pathologies.Peer reviewe