Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04179 (
MnSOD
)
2,777
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Abacavir
(
ABC
) is a guanosine nucleoside reverse transcriptase inhibitor (NRTI) with potent antiretroviral activity. Since NRTIs exhibit tissue-specific inhibition of mitochondrial DNA (mtDNA) synthesis, the ability of
ABC
to inhibit mtDNA synthesis in vivo was evaluated. Inbred wild-type (WT) and transgenic mice (TG) treated with
ABC
(3.125 mg/d p. o., 35 days) were used to define mitochondrial oxidative stress and cardiac function. Chosen TGs exhibited overexpression of HIV-1 viral proteins (NL4-3Deltagag/pol, non-replication competent), hemizygous depletion or overexpression of mitochondrial superoxide dismutase (SOD2(+/-) knock-out (KO) or
MnSOD
OX, respectively), overexpression of mitochondrially targeted catalase (MCAT), or double "knockout" deletion of aldehyde dehydrogenase activity (ALDH2 KO). Impact on mtDNA synthesis was assessed by comparing changes in mtDNA abundance between
ABC
-treated and vehicle-treated WTs and TGs. No changes in mtDNA abundance occurred from
ABC
treatment in any mice, suggesting no inhibition of mtDNA synthesis. Left ventricle (LV) mass and LV end-diastolic dimension (LVEDD) were defined echocardiographically and remained unchanged as well. These results indicate that treatment with
ABC
has no visible cardiotoxicity in these adult mice exposed for 5 weeks compared to findings with other antiretroviral NRTI studies and support some claims for its relative safety.
...
PMID:Absence of mitochondrial toxicity in hearts of transgenic mice treated with abacavir. 2037 2
