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Mildronate's protective effects in the peripheral nervous system: stavudine-induced neuropathy and formalin-induced inflammation 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. Mildronāta protektīvie efekti perifērajā nervu sistēmā: stavudīna neiropātijas un formalīna iekaisuma modeļi Iepriekšējos pētījumos esam parādījuši mildronāta spēju regulēt mitohondriālos procesus izolētos žurku aknu audos, kā arī normalizēt smadzeņu audu dažādu signālmolekulu ekspresiju. Šajā darbā pārbaudījām hipotēzi, ka mildronāts spēj uzrādīt protektīvu darbību arī perifērajā nervu sistēmā. To pētījām modeļvielas — stavudīna izrasītās neiropātijas modelī un formalīna izraisītā iekaisuma procesos. Mildronāts devā 100 mg/kg būtiski samazināja stavudīna izraisīto degeneratīvo šūnu skaitu žurku perifērajos (sēžas nerva) nervu audos, taču neietekmēja samazināto mielīna ekspresiju. Mildronāts līdz kontroles līmenim samazināja iekaisuma reakciju formalīna testa otrajā fāzē, un rezultāts bija salīdzināms ar indometacīna efektu. Šie rezultāti liecina, ka mildronāts spēj regulēt degeneratīvos un iekaisuma procesus perifērajā nervu sistēmā, ko var izskaidrot ar tā spēju regulēt mitohondriālos procesus. Iegūtie dati norāda uz mildronāta iespējamiem protektīvajiem efektiem perifēro neirologisko saslimšanu (piemēram, neiropātiju) ārstēšanā.

proceedings of the latvian academy of sciences. section b, natural sciences/latvijas zinātņu akadēmijas vēstis. a daļa, humanitārās un sociālās zinātnes