Oxidative Damage is not a Major Contributor to AZT-Induced Mitochondrial Mutations

Osborne, Adam

doi:10.4172/2155-6113.1000441

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…The fact that AZT enhanced the cytostatic activity of PFJ argues against PFJ degrading AZT. Independent studies also show that AZT remains active in the presence of PFJ [23]. The cytostatic activity of PFJ appears to arise from changes in gene expression that lead to G1/S phase arrest [44].…”

Section: Protective Effects Of Pfj Against Azt Cytotoxicitymentioning

confidence: 97%

“…AZT treatment increases oxidative stress in cells and causes mutagenesis and dose-dependent cytotoxicity, but the biochemical basis for these phenomena remains unclear. Since PFJ is rich in antioxidants and many antioxidants are known to modulate Reactive Oxygen Species (ROS) [23] it is logical to postulate that PFJ suppresses mutations caused by ROS. However, PFJ only reduced the number of AZT-induced mutations by 65%, suggesting that only a fraction of the mutations arise because of an increase in ROS and that the AZT also acts by ROS independent mechanisms.…”

Section: Protective Effects Of Pfj Against Azt Mutagenesismentioning

confidence: 99%

“…Palm fruit juice is a water soluble by-product of oil extraction from the fruit of the oil palm (Elaeis guineensis) that is rich in antioxidant phenolics [20,21]. Palm fruit juice has high scavenging activity against hydrogen peroxide, the main contributor to reactive oxygen species (ROS) produced in mitochondria [20,22,23]. Palm fruit juice also exhibits various protective biological effects, including antiatherogenic, anti-inflammatory, anti-diabetic, and anti-neoplastic properties [24][25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

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Palm Fruit Juice Mitigates AZT Mitochondrial Genotoxicity and Dose- Dependent Cytotoxicity

Ae¹,

Ja²,

Solomon³

et al. 2014

J AIDS Clin Res

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Chronic use of 3′-Azido-3′-deoxythymidine (AZT) to treat HIV/AIDS causes mitochondrial dysfunction and the accumulation of mitochondrial mutations. These toxicities have been attributed to increased oxidative damage, among other mechanisms. Palm fruit juice (PFJ), also known as oil palm phenolics (OPP), is a water soluble byproduct of oil extraction from the fruit of the oil palm (Elaeis guineensis) that is rich in antioxidants and other phytochemicals. The capacity of PFJ to mitigate AZT mitochondrial genotoxicity (mutagenesis) as well as dosedependent cytotoxicity were measured in cultured HepG2 cells. In the presence of PFJ, AZT-induced mutations were 35% the number of mutations observed in samples treated with AZT alone in the three regions of the mitochondrial genome examined (HV2, CO2, and ND1). Co-treatment with PFJ increased cell survival in the presence of increasing doses of AZT by up to 350%. These effects were not due to degradation or inactivation of AZT by PFJ. The discovery of the mitigating effects of PFJ provides a potential means of ameliorating AZT-induced mutations and possibly other long-term negative side effects of long-term AZT use.

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Section: Protective Effects Of Pfj Against Azt Cytotoxicitymentioning

confidence: 97%

Section: Protective Effects Of Pfj Against Azt Mutagenesismentioning

confidence: 99%