<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>Previously we showed that mildronate effectively protected mice heart tissue against the toxic influence of anti-HIV drugs azidothymidine, stavudine and lamivudine, which belong to nucleosideanalogue reverse transcriptase inhibitor (NRTI) class. Recently we also demonstrated that mildronate protected isolated rat liver mitochondria against mitochondrial damage caused by azidothymidine. The present study was devoted to examine the possible protective effectiveness of mildronate in cardio-, hepato- and neurotoxicity models caused by anti-HIV drugs of other classes: indinavir, a representative of protease inhibitor (PI) class, and efavirenz, a non-nucleoside-analogue reverse transcriptase inhibitor (NNRTI). Drugs were administered intraperitoneally for two weeks, at the dose of 50 mg/kg of anti-HIV drugs and 100 mg/kg for mildronate. Afterwards, mice heart, liver and brain tissue were examined morphologically and immunohistochemically. The results showed that indinavir in heart tissue caused inflammatory and degenerative changes, manifested as increased expression of nuclear factor kappaBp65 (NF-kBp65), as well as cardiomyocyte necrosis and cellular infiltration. Efavirenz did not cause pathological changes in mice heart tissue, whereas it induced marked expression of caspase-3 and glial fibrillary acidic protein (GFAP) in mice brain tissue and small degenerative alterations in mice liver tissue. The data obtained show mildronate's protective properties in indinavir-induced cardiotoxicity and efavirenz-induced neurotoxicity.</p></abstract>

Previously we showed that mildronate effectively protected mice heart tissue against the toxic influence of anti-HIV drugs azidothymidine, stavudine and lamivudine, which belong to nucleosideanalogue reverse transcriptase inhibitor (NRTI) class. Recently we also demonstrated that mildronate protected isolated rat liver mitochondria against mitochondrial damage caused by azidothymidine. The present study was devoted to examine the possible protective effectiveness of mildronate in cardio-, hepato- and neurotoxicity models caused by anti-HIV drugs of other classes: indinavir, a representative of protease inhibitor (PI) class, and efavirenz, a non-nucleoside-analogue reverse transcriptase inhibitor (NNRTI). Drugs were administered intraperitoneally for two weeks, at the dose of 50 mg/kg of anti-HIV drugs and 100 mg/kg for mildronate. Afterwards, mice heart, liver and brain tissue were examined morphologically and immunohistochemically. The results showed that indinavir in heart tissue caused inflammatory and degenerative changes, manifested as increased expression of nuclear factor kappaBp65 (NF-kBp65), as well as cardiomyocyte necrosis and cellular infiltration. Efavirenz did not cause pathological changes in mice heart tissue, whereas it induced marked expression of caspase-3 and glial fibrillary acidic protein (GFAP) in mice brain tissue and small degenerative alterations in mice liver tissue. The data obtained show mildronate's protective properties in indinavir-induced cardiotoxicity and efavirenz-induced neurotoxicity.

Protective effects of mildronate in indinavir- and efavirenz-induced toxicity in mice

Faculty of Medicine, University of Latvia, Šarlotes iela 1A, Rīga, LV-1001, LATVIA

Latvian Institute of Organic Synthesis, Aizkraukles iela 21, Rīga, LV-1006, LATVIA

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

Previously we showed that mildronate effectively protected mice heart tissue against the toxic influence of anti-HIV drugs azidothymidine, stavudine and...

Protective effects of mildronate in indinavir- and efavirenz-induced toxicity in mice

Publié en ligne: 25 janv. 2011

Pages: 119 - 124

DOI: https://doi.org/10.2478/v10046-010-0025-6

Mots clés
mildronate, indinavir cardiotoxicity, efavirenz neurotoxicity

This content is open access.

Protective effects of mildronate in indinavir- and efavirenz-induced toxicity in mice

Publié en ligne: 25 janv. 2011

Pages: 119 - 124

DOI: https://doi.org/10.2478/v10046-010-0025-6

Mots clésmildronate, indinavir cardiotoxicity, efavirenz neurotoxicity

This content is open access.

Mots clés
mildronate, indinavir cardiotoxicity, efavirenz neurotoxicity