Mitochondrial Toxicity of Tenofovir Dipivoxil Fumarate in HK-2 Cells
Qihui Luo, Junjun Zhao, Xing-Lei Feng, Zhengli Chen, Wen Zeng, Li Gong, Anchun Cheng, Yubo Shen, Chunmei Zhu
Abstract
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Qihui Luo, Junjun Zhao, Xing-Lei Feng, Zhengli Chen, Wen Zeng, Li Gong, Anchun Cheng, Yubo Shen, Chunmei Zhu
Abstract
Open-access reader
Nucleoside analogs have been shown to have mitochondrial toxicity.In vitro tests can evaluate the mechanisms and severity of the toxicity.Tenofovir dipivoxil fumarate (TDF) is a novel drug for type B hepatitis.In this study, HK-2 cells were used to evaluate the effect of TDF on mitochondrial toxicity in the kidney.HK-2 cells were treated for 9 days in seven treatment groups.This study measured the inhibitory rate of cell proliferation, lactic acid levels, activities of mitochondrial respiratory chain complexes I-III, and mitochondrial DNA content as well as mitochondrial ultrastructure.Results exhibited that rates of cell proliferation, activities of complexes I, III and mitochondrial DNA content were reduced, but lactic acid levels increased in the 125 μM TDF group.Mitochondrial ultrastructure was damaged in the 125 μM TDF and 62.5 μM TDF groups.Thus, the 125 μM TDF group exhibited noticeable mitochondrial toxicity, whereas 62.5 μM TDF presented weak mitochondrial toxicity, and 31.25 μM TDF exhibited no obvious mitochondrial toxicity.
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Nucleoside analogs have been shown to have mitochondrial toxicity.In vitro tests can evaluate the mechanisms and severity of the toxicity.Tenofovir dipivoxil fumarate (TDF) is a novel drug for type B hepatitis.In this study, HK-2 cells were used to evaluate the effect of TDF on mitochondrial toxicity in the kidney.HK-2 cells were treated for 9 days in seven treatment groups.This study measured the inhibitory rate of cell proliferation, lactic acid levels, activities of mitochondrial respiratory chain complexes I-III, and mitochondrial DNA content as well as mitochondrial ultrastructure.Results exhibited that rates of cell proliferation, activities of complexes I, III and mitochondrial DNA content were reduced, but lactic acid levels increased in the 125 μM TDF group.Mitochondrial ultrastructure was damaged in the 125 μM TDF and 62.5 μM TDF groups.Thus, the 125 μM TDF group exhibited noticeable mitochondrial toxicity, whereas 62.5 μM TDF presented weak mitochondrial toxicity, and 31.25 μM TDF exhibited no obvious mitochondrial toxicity.
Key concepts: Mitochondrial toxicity, Tenofovir, Toxicity, Chemistry, Biology, Virology, Human immunodeficiency virus (HIV), Organic chemistry