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Abacavir (ABC) Has No Cardiac Mitochondrial Toxicity in Multiple Trangenic Murine Models Compared to Zidovudine (AZT)
Author(s) -
Kohler James J,
Hosseini Seyed H.,
Koczor Christopher A.,
Fields Earl,
Green Elgin,
Abuin Allison,
Ludaway Tomika,
Russ Rodney,
Zhao Peter,
Lewis William
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1029.2
Subject(s) - sod2 , oxidative stress , zidovudine , abacavir , mitochondrial toxicity , pharmacology , superoxide dismutase , aldh2 , didanosine , mitochondrial dna , chemistry , mitochondrion , toxicity , medicine , virology , biochemistry , aldehyde dehydrogenase , lamivudine , enzyme , human immunodeficiency virus (hiv) , virus , viral disease , hepatitis b virus , gene
ABC and AZT are both nucleoside reverse transcriptase inhibitors (NRTIs) central to effective antiretroviral therapy for HIV/AIDS. Despite therapeutic success, toxicities associated with NRTI‐induced mitochondrial dysfunction have been reported. Genetically engineered mice with knock‐out (KO) or overexpression (OX) of mitochondrial superoxide dismutase (SOD2+/− KO and SOD2‐OX, respectively), mitochondrially targeted catalase (mCAT‐TG), aldehyde dehydrogenase 2 (ALDH2 KO), alcohol dehydrogenase (ADH‐TG), or wild‐type littermates (C57/BL6, WT) were treated with AZT (0.22 mg/d) or ABC (3.125 mg/d) for 35 days. Mitochondrial DNA (mtDNA) abundance and left‐ventricle (LV) mass and LV end‐diastolic dimension were determined. AZT induced cardiac oxidative stress and LV dysfunction in WTs. Effects worsened in KOs while OX and TGs prevented or attenuated AZT‐induced cardiac oxidative stress. Conversely, ABC had no effect on any cohorts, including WTs, suggesting no associated cardiac oxidative stress with ABC. These data support the clinical use of ABC as replacement for AZT in preventing cardiac oxidative stress.