PUBLICATION

Tenofovir and bone: age-dependent effects in a zebrafish animal model

Authors
Carnovali, M., Banfi, G., Mora, S., Mariotti, M.
ID
ZDB-PUB-160402-2
Date
2016
Source
Antiviral therapy   21(7): 587-594 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Age Factors
  • Animals
  • Anti-HIV Agents/toxicity*
  • Bone and Bones/drug effects*
  • Bone and Bones/metabolism
  • Calcification, Physiologic/drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Models, Animal
  • Osteoblasts/drug effects
  • Osteogenesis/drug effects
  • Tenofovir/toxicity*
  • Zebrafish
PubMed
27035702 Full text @ Antivir. Ther. (Lond.)
Abstract
New drugs against human immunodeficiency virus (HIV) infection are associated with important side effects, including impaired bone health. An important reduction of bone mineral density has been repeatedly described in adult but not in young patients receiving tenofovir disoproxil fumarate (TDF) as part of their antiretroviral regimen.The present study was to verify the presence and the characteristics of the adverse effects of TDF on skeletal tissue by using the Danio rerio (zebrafish) model.
TDF administration via microinjection in the yolk has been used for embryo study. Water treatment with TDF and scale analysis by morphological, histological and biochemical experiments have been used for adult animals.
TDF administration via microinjection in the yolk did not induce any significant effect on mineralization rate and did not produce deformity of the skeletal structure as well as growth or vitality impairment of the embryos. TDF exposure to adult zebrafish induced an age-related reduction of the osteoblastic activity marker ALP (up to -44%) and an increase of the osteoclastic activity marker TRAP (up to +57%) in the scales. Old fish treated with TDF exhibited an osteoporotic-like phenotype with resorption area along the edge of the scale.
This study demonstrated that in zebrafish as in humans TDF shows a catabolic bone effect related to the age and underlined the ultimate utility of using teleost fish as model to assess the effects of drug on bone tissue.
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