Sammanfattning

Vitamin D metabolism was studied in primary human dermal fibroblasts with focus on drug-mediated gene regulation related to adverse side effects of antiretroviral drugs used in HIV therapy. The fibroblasts expressed mRNA for cytochrome P450 (CYP) enzymes catalysing bioactivating (CYP2R1, CYP27A1 and CYP27B1) and catabolic reactions (CYP24A1). The cells produced both 25-hydroxyvitamin D-3 and 1 alpha,25-dihydroxyvitamin D-3. The results demonstrate that primary dermal fibroblasts have an active vitamin D-3-metabolizing system. High incidence of low bone mineral density is a concern for HIV-infected patients treated with antiretroviral drugs. Osteomalacia and severe vitamin D deficiency have been reported. We investigated whether drug-mediated gene regulation could be a possible mechanism behind these adverse drug effects. Fibroblasts were treated with different drugs used in HIV therapy, and the 1 alpha,25-dihydroxyvitamin D-3 levels and relative mRNA levels for crucial enzymes were determined. Efavirenz, stavudine and ritonavir significantly down-regulated the bioactivating CYP2R1 and up-regulated the catabolic CYP24A1. The drugs reduced bioactivating enzyme activities and cellular levels of 1 alpha,25-dihydroxyvitamin D-3. The current results indicate that effects on gene expression may lead to disturbed vitamin D metabolism and decreased cellular levels of active vitamin D-3. The data are consistent with the impaired bone health in patients treated with certain antiretroviral drugs.

Publicerad i

Basic and Clinical Pharmacology and Toxicology
2017, Volym: 120, nummer: 1, sidor: 59-63

Globala målen

SDG3 Säkerställa hälsosamma liv och främja välbefinnande för alla i alla åldrar


UKÄ forskningsämne

Farmakologi och toxikologi


Publikationens identifierare

DOI: https://doi.org/10.1111/bcpt.12641

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/88791