Long-Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats.
Animals
Anti-HIV Agents
/ administration & dosage
Bone Density
/ drug effects
Bone and Bones
/ drug effects
Catalase
/ metabolism
Dideoxynucleosides
/ administration & dosage
Glutathione
/ metabolism
Glutathione Peroxidase
/ metabolism
Kidney
/ drug effects
Liver
/ drug effects
Male
Malondialdehyde
/ metabolism
Nitriles
/ administration & dosage
Oxidative Stress
Pyrimidines
/ administration & dosage
Rats
Rats, Wistar
Semen
/ drug effects
Superoxide Dismutase
/ metabolism
Testis
/ drug effects
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2021
2021
Historique:
received:
10
02
2021
revised:
24
05
2021
accepted:
05
07
2021
entrez:
10
8
2021
pubmed:
11
8
2021
medline:
7
1
2022
Statut:
epublish
Résumé
Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients' life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide-redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide-redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young's modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D
Identifiants
pubmed: 34373766
doi: 10.1155/2021/5596090
pmc: PMC8349296
doi:
Substances chimiques
Anti-HIV Agents
0
Dideoxynucleosides
0
Nitriles
0
Pyrimidines
0
etravirine
0C50HW4FO1
Malondialdehyde
4Y8F71G49Q
Catalase
EC 1.11.1.6
Glutathione Peroxidase
EC 1.11.1.9
Superoxide Dismutase
EC 1.15.1.1
Glutathione
GAN16C9B8O
abacavir
WR2TIP26VS
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5596090Informations de copyright
Copyright © 2021 Agnieszka Matuszewska et al.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest regarding the publication of this paper.
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