Combination antiretroviral therapy (cART)-induced hippocampal disorders: Highlights on therapeutic potential of Naringenin and Quercetin

Autor: Alani S Akanmu, Olufunke O. Dosumu, Daniel D. Osiagwu, Adeola M. Fagoroye, Isilamiyat T. Usman, Olasunmbo O. Afolayan, Ademola A Oremosu, E. N. Akang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Naringenin
GSH
reduced glutathione
Morris water navigation task
Pharmacology
DMSO
dimethyl sulfoxide
medicine.disease_cause
Hippocampus
chemistry.chemical_compound
0302 clinical medicine
immune system diseases
HCL
hydrochloric acidE
Medicine
heterocyclic compounds
biology
General Neuroscience
cART
combination antiretroviral therapy
virus diseases
food and beverages
ELISA
enzyme-linked immunosorbent assay
Malondialdehyde
3. Good health
Nar
naringenin
Quercetin
Quer
quercetin
MAO-B
monoamine oxidase B
TNFα
tumor necrosis factor alpha
cART
DTA
ethylenediaminetetraacetic acid
TBA
thiobarbituric acid
Article
lcsh:RC321-571
Superoxide dismutase
03 medical and health sciences
ROS
reactive oxygen species
SOD
superoxide dismutase
Neurodegeneration
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
MDA
malondialdehyde
cA/N
24 mg/kg combination antiretroviral therapy + 50 mg Naringenin
business.industry
Dentate gyrus
Glutathione
CA/Q
24 mg/kg combination antiretroviral therapy + 50 mg Quercetin
030104 developmental biology
chemistry
nervous system
Oxidative stress
biology.protein
CAT
catalase
business
030217 neurology & neurosurgery
Zdroj: IBRO Reports
IBRO Reports, Vol 6, Iss, Pp 137-146 (2019)
ISSN: 2451-8301
Popis: Highlights • Naringenin and Quercetin decrease ROS and potentiate enzymatic antioxidant production in the hippocampus. • cART induced marked cytoplasmic shrinkage and several pyknotic nuclei in the dentate gyrus and cornus ammonis region. • Naringenin and Quercetin attenuates cART-induced upregulation of monoamine oxidase-B expression in neurons. • Naringenin and Quercetin also ameliorates cART-induced spatial memory impairments. • Naringenin and Quercetin acted as effective antioxidants in vivo against cART-induced neurotoxicity.
Introduction In spite of the multiple benefits of combination antiretroviral therapy (cART) on HIV positive patients, prolonged usage has been reported to exacerbate oxidative stress, and induce neurological and cognitive dysfunction, thus, the need to search for an adjuvant therapy to ameliorate the oxidative and improve treatment adherence with better virological outcome. This study aimed at determining the potential therapeutic effects of Quercetin and Naringenin on cART-induced cyto-architectural, neuro-behavioral and immunohistochemical changes in the hippocampus of the adult Wister rats. Materials and Methods The animals were grouped as follows: Control, DMSO, 24 mg/kg cART (Tenovovir 300 mg, Lamivudine 300 mg and Efavirenz 600 mg), 50 mg/kg Naringenin, 50 mg/kg Quercetin, cART + Naringenin, cART + Quercetin were administered orally for 8 weeks. At the end of administration, neurobehavioural test was conducted, animals were euthanized and hippocampus was processed for oxidative stress markers, histology, TNF-α, and Monoamine oxidase-B expression. Results At the end of 8 weeks of administration, 24 mg/kg cART decreased superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and increased Malondialdehyde (MDA). Whereas, 50 mg/kg quercetin, and 50 mg/kg Naringenin decreased the oxidative stress (increased SOD, CAT, GSH, and reduced MDA) induced by cART (reduced SOD, CAT, GSH, and increased MDA). In addition, hematoxylin and eosin stained hippocampus showed that quercetin and naringenin prevented neurodegenerative changes (marked cytoplasmic shrinkage and several pyknotic nuclei in the dentate gyrus and cornus ammonis regions) in cART-treated rats. Furthermore, immunohistochemical studies revealed that quercetin and naringenin attenuates cART-induced upregulation of monoamine oxidase-B (MAO-B) expression. Likewise, from the Morris water maze neurobehavioral studies, naringenin and quercetin also ameliorated cART-induced memory impairments (initial spatial memory, reversal spatial memory and probe tests). Conclusion This study shows that Naringenin and Quercetin have a good potential in reversing cART-induced hippocampal disorders in Wistar rats.
Databáze: OpenAIRE
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