Farnesyltransferase inhibitors prevent HIV protease inhibitor (Lopinavir/ritonavir)-induced lipodystrophy and metabolic syndrome in mice

Tomokazu Tanaka, Harumasa Nakazawa, Naohide Kuriyama, Masao Kaneki

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Highly active antiretroviral therapy (HAART) has successfully reduced the mortality rate of patients with human immune deficiency virus (HIV) and HIV protease inhibitors (HIV PIs) are key components of HAART. Complications of HAART, particularly those associated with HIV PIs including lipodystrophy and metabolic disturbance, have emerged as an important public health issue. No specific treatment is available to prevent and/or treat HIV PI-associated lipodystrophy and metabolic syndrome. The present study demonstrated that a relatively low-dose of farnesyltransferase inhibitor (FTI), tipifarnib (3 mg/kg/day, subcutaneous injection) and lonafarnib (5 mg/kg/day, subcutaneous injection), prevented the onset of lipodystrophy and metabolic syndrome induced by the combination of two HIV PIs, lopinavir (50 mg/kg/day, intraperitoneal injection) and ritonavir (12.5 mg/kg/day, intraperitoneal injection), in mice. Consistent with previous studies, treatment with lopinavir/ritonavir for 2 weeks decreased body weight, adipose tissue mass, levels of plasma adiponectin and leptin, and increased plasma levels of triglycerides, total cholesterol and insulin. Tipifarnib and lonafarnb prevented or ameliorated all of these alterations in the HIV PI-treated mice. These data identify FTIs as a novel potential strategy to prevent or treat HIV PI-associated lipodystrophy and metabolic syndrome in HIV-infected patients on HAART.

本文言語English
ページ(範囲)1314-1320
ページ数7
ジャーナルExperimental and Therapeutic Medicine
15
2
DOI
出版ステータスPublished - 02-2018
外部発表はい

All Science Journal Classification (ASJC) codes

  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

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