HIV protease inhibitor ritonavir induces renal fibrosis and dysfunction: role of platelet-derived TGF-β1 and intervention via antioxidant pathways.

ABSTRACT:

Objective

Chronic kidney disease (CKD) with tubular injury and fibrosis occurs in HIV infection treated with certain protease inhibitor-based antiretroviral therapies. The pathophysiology is unclear.

Design

We hypothesized that fibrosis, mediated by platelet-derived transforming growth factor (TGF)-β1, underlies protease inhibitor-associated CKD. We induced this in mice exposed to the protease inhibitor ritonavir (RTV), and intervened with low-dose inhaled carbon monoxide (CO), activating erythroid 2-related factor (Nrf2)-associated antioxidant pathways.

Methods

Wild-type C57BL/6 mice and mice deficient in platelet TGF-β1, were given RTV (10 mg/kg) or vehicle daily for 8 weeks. Select groups were exposed to CO (250 ppm) for 4 h after RTV or vehicle injection. Renal di

SUBMITTER: Laurence J 

PROVIDER: S-EPMC7210074 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature