Insights into Gastrointestinal Redox Dysregulation in a Rat Model of Alzheimer’s Disease and the Assessment of the Protective Potential of D-Galactose DOI Creative Commons
Jan Homolak, Konstantinos Varvaras,

Vittorio Sciacca

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(10), P. 11288 - 11304

Published: Feb. 27, 2024

Recent evidence suggests that the gut plays a vital role in development and progression of Alzheimer's disease (AD) by triggering systemic inflammation oxidative stress. The well-established rat model AD, induced intracerebroventricular administration streptozotocin (STZ-icv), provides valuable insights into GI implications neurodegeneration. Notably, this leads to pathophysiological changes gut, including redox dyshomeostasis, resulting from central neuropathology. Our study aimed investigate mechanisms underlying dyshomeostasis assess effects D-galactose, which is known benefit homeostasis alleviate cognitive deficits model. Duodenal rings isolated STZ-icv animals control groups were subjected prooxidative environment using 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) or H2O2 with without D-galactose oxygenated Krebs buffer ex vivo. Redox was analyzed through protein microarrays functional biochemical assays alongside cell survival assessment. Structural equation modeling univariate multivariate models employed evaluate differential response samples controlled challenge. showed suppressed expression catalase glutathione peroxidase 4 (GPX4) increased baseline activity enzymes involved superoxide homeostasis. altered status associated an inability respond challenges D-galactose. Conversely, presence antioxidant capacity, enhanced activity, upregulated dismutases samples. STZ-icv-induced dysfunction characterized diminished ability regulatory system maintain long-term protection transcription genes as well compromised activation responsible for immediate defense. can exert beneficial on under physiological conditions.

Language: Английский

The Absence of Gastrointestinal Redox Dyshomeostasis in the Brain-First Rat Model of Parkinson’s Disease Induced by Bilateral Intrastriatal 6-Hydroxydopamine DOI Creative Commons
Jan Homolak, Mihovil Joja, Gracia Grabarić

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5481 - 5493

Published: Jan. 10, 2024

The gut-brain axis plays an important role in Parkinson's disease (PD) by acting as a route for vagal propagation of aggregated α-synuclein the gut-first endophenotype and mediator gastrointestinal dyshomeostasis via nigro-vagal pathway brain-first disease. One mechanism which may promote PD is regulating redox homeostasis overwhelming evidence suggests that oxidative stress key etiopathogenesis progression tract maintains organism critical barrier to environmental microbiological electrophilic challenges. present aim was utilize bilateral intrastriatal 6-hydroxydopamine (6-OHDA) model study effects isolated central pathology on tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or bilaterally intrastriatally with vehicle (CIS) 6-OHDA (6-OHDA). Motor deficits assessed rotarod performance test, duodenum, ileum, colon dissected biochemical analyses 12 weeks after treatment. Lipid peroxidation, total antioxidant capacity, low-molecular-weight thiols, protein sulfhydryls, activity Mn/Fe superoxide dismutases, azide-insensitive catalase/peroxidase measured. Both univariate multivariate models analyzing biomarkers indicate significant disturbances balance are present. findings demonstrate motor impairment observed can occur without concurrent imbalances system.

Language: Английский

Citations

5
Insights into Gastrointestinal Redox Dysregulation in a Rat Model of Alzheimer’s Disease and the Assessment of the Protective Potential of D-Galactose DOI Creative Commons
Jan Homolak, Konstantinos Varvaras,

Vittorio Sciacca

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(10), P. 11288 - 11304

Published: Feb. 27, 2024

Recent evidence suggests that the gut plays a vital role in development and progression of Alzheimer's disease (AD) by triggering systemic inflammation oxidative stress. The well-established rat model AD, induced intracerebroventricular administration streptozotocin (STZ-icv), provides valuable insights into GI implications neurodegeneration. Notably, this leads to pathophysiological changes gut, including redox dyshomeostasis, resulting from central neuropathology. Our study aimed investigate mechanisms underlying dyshomeostasis assess effects D-galactose, which is known benefit homeostasis alleviate cognitive deficits model. Duodenal rings isolated STZ-icv animals control groups were subjected prooxidative environment using 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) or H2O2 with without D-galactose oxygenated Krebs buffer ex vivo. Redox was analyzed through protein microarrays functional biochemical assays alongside cell survival assessment. Structural equation modeling univariate multivariate models employed evaluate differential response samples controlled challenge. showed suppressed expression catalase glutathione peroxidase 4 (GPX4) increased baseline activity enzymes involved superoxide homeostasis. altered status associated an inability respond challenges D-galactose. Conversely, presence antioxidant capacity, enhanced activity, upregulated dismutases samples. STZ-icv-induced dysfunction characterized diminished ability regulatory system maintain long-term protection transcription genes as well compromised activation responsible for immediate defense. can exert beneficial on under physiological conditions.

Language: Английский

Citations

2