Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 19, 2024

Introduction: Nephrotoxicity represents a major complication of using doxorubicin (DOX) in the management several types cancers. Increased oxidative stress and activation inflammatory mediators play outstanding roles development DOX-induced kidney damage. This study aimed to investigate whether two pathways incretin-based therapy, glucagon-like peptide-1 receptor agonist (presented as semaglutide, SEM) dipeptidyl peptidase-4 inhibitor alogliptin, ALO), differentially protect against nephrotoxicity rats clarify underlying molecular mechanisms. Methods: Adult male were divided into six groups: control (received vehicle), DOX (20 mg/kg, single I.P. on day 8), + ALO mg/kg/day, P.O. for 10 days), SEM (12 μg/kg/day, S.C. ALO-alone, SEM-alone groups. At end study, animals sacrificed their functions, stress, markers assessed. Kidney sections also subjected histopathological examinations. Results: The co-treatment with either or manifested an improvement evidenced by lower serum concentrations creatinine, urea, cystatin C compared group. Lower levels MDA, higher GSH, increased SOD activity observed ALO- SEM-treated groups than those administration resulted decreased renal expressions sirtuin 1 (SIRT1) Nrf2 NF-κB TNF-α expressions, these effects ameliorated treatment SEM. Discussion: Co-treatment showed renoprotective effect that was mediated antioxidant anti-inflammatory via SIRT1/Nrf2/NF-κB/TNF-α pathway. fact both therapy demonstrate equally positive alleviating damage is noteworthy.

Язык: Английский

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A Systematic Review of Semaglutide’s Influence on Cognitive Function in Preclinical Animal Models and Cell-Line Studies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4972 - 4972

Опубликована: Май 2, 2024

Since we aim to test new options find medication for cognitive disorders, have begun assess the effect of semaglutide and conduct a review gathering studies that attempted this purpose. This systematic focuses on effects semaglutide, glucagon-like peptide 1 receptor agonist (GLP-1 RA), in context neurological impairment. Semaglutide, synthetic GLP-1 analog, showcased neuroprotective beyond metabolic regulation. It mitigated apoptosis improved dysfunction cerebrovascular disease, suggesting broader implications well-being. Also, highlighted RAs’ positive impact olfactory function obese individuals with type 2 diabetes, neurodegenerative multiple sclerosis, endotoxemia. In order analyze current function, literature search was conducted up February 2024 two online databases, MEDLINE (via PubMed) Web Science Core Collection, as well various websites. Fifteen mice populations cell lines were included, analyzed, assessed bias-specific tools. The anti-apoptotic properties its analogs emphasized, animal models line demonstrating enhanced function. While promising, limitations include fewer studies, highlighting need extensive research, particularly human population. Even though seems there are significant limitations, one which is lack subjects. Therefore, aims gather evidence.

Язык: Английский

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Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Язык: Английский

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Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway

Inflammopharmacology, Год журнала: 2023, Номер 32(2), С. 1499 - 1518

Опубликована: Дек. 19, 2023

Abstract Multiple sclerosis (MS) is an incurable chronic neurodegenerative disease where autoimmunity, oxidative stress, and neuroinflammation collaboration predispose myelin sheath destruction. Interestingly, curcumin, a natural polyphenol, showed neuroprotective effect in numerous diseases, including MS. Nevertheless, the influence of curcumin against MS-induced cognitive impairment still vague. Hence, we induced experimental autoimmune encephalomyelitis (EAE) mice using spinal cord homogenate (SCH) complete Freund’s adjuvant, which eventually mimic This study aimed not only to evaluate efficacy EAE-induced motor dysfunction, but also explore novel mechanism action, by exerts its beneficial effects Curcumin (200 mg/kg/day) was evaluated behavioral tests, histopathological examination, biochemical tests. Concisely, amended impairments, as demonstrated tests examination hippocampus. activated adenosine monophosphate (AMP)-activated protein kinase/silent mating type information regulation 2 homolog 1 (AMPK/SIRT1) axis, triggered cyclic AMP response element-binding protein/brain-derived neurotrophic factor/myelin basic (CREB/BDNF/MBP) pathway, hindering demyelination corpus callosum. Furthermore, AMPK/SIRT1 activation augmented nuclear factor erythroid 2-related (Nrf2), powerful antioxidant, amending stress. Additionally, abolished inhibiting Janus kinase /signal transducers activators transcription 3 (JAK2/STAT3) various pathways, activation. JAK2/STAT3 inhibition halts inflammatory cytokines synthesis. In conclusion, curcumin’s EAE controlled, at least part, activation, ultimately minimizes neuronal demyelination, neuroinflammation. Graphical illustration putative molecular pathways implicated management curcumin. activates AMPK/SIRT1, turn multiple that hinder neurodegeneration, Moreover, conquers pathway JAK2/STAT3/NF-kβ.

Язык: Английский

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Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(6), С. 5929 - 5949

Опубликована: Июнь 13, 2024

Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s (PD). This review provides comprehensive description of SEM’s mechanism action preclinical studies these debilitating conditions. In animal models AD, SEM proved beneficial on multiple pathological hallmarks the disease. administration been associated with reductions amyloid-beta plaque deposition mitigation neuroinflammation. Moreover, treatment shown to ameliorate behavioral deficits related anxiety social interaction. SEM-treated animals exhibit improvements spatial learning memory retention tasks, evidenced by enhanced performance maze navigation tests novel object recognition assays. Similarly, PD, demonstrated promising neuroprotective through various mechanisms. These include modulation neuroinflammation, enhancement mitochondrial function, promotion neurogenesis. Additionally, improve motor function dopaminergic neuronal loss, offering disease-modifying strategies. Overall, accumulating evidence from suggests that holds promise approach AD PD. Further research is warranted elucidate underlying mechanisms translate findings into clinical applications devastating disorders.

Язык: Английский

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The SIRT-1/Nrf2/HO-1 Axis: Guardians of Neuronal Health in Neurological Disorders

Behavioural Brain Research, Год журнала: 2024, Номер unknown, С. 115280 - 115280

Опубликована: Окт. 1, 2024

Язык: Английский

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Neuroprotective effects of semaglutide and metformin against rotenone-induced neurobehavioral changes in male diabetic rats

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Abstract Pre-existing diabetes raises the likelihood of Parkinson’s disease (PD), according to epidemiological and animal research. Our study aimed investigating likely neuroprotective effect metformin (Met) and/or semaglutide (Sem) in model PD male diabetic rats possible underlying mechanism. Type 2 (T2DM) was induced by giving high-fat diet (HFD) for 3 weeks followed a single streptozotocin (STZ) injection (40 mg/kg, i.p., once dose) 9 doses rotenone every 48 ± h induction PD. Met Sema were administered DM+PD via gastric gavage daily 4 weeks. In comparison with group, Sem significantly lowered blood glucose levels, HOMA-IR, HbA1C, cholesterol, triglycerides, LDL increased insulin HDL levels. addition, there enhanced brain antioxidant status lower oxidative-inflammatory stress biomarkers associated improved rat cognitive, locomotor, olfactory functions. A significant downregulation caspase GFAP concomitant upregulation NRF2 protein expressions observed treated groups. Overall, co-treatment elicited more efficacy than that individual regimen. When combined, results this have demonstrated first time work concert create neuroprotection compared when taken separately. The study’s findings indicate restorative on T2DM PD-induced changes neurobehavioral biochemical/molecular indices ascribed improvement endogenous systems, decreased lipid peroxidation, suppression oxidative/inflammatory stress, and—most importantly—regulation Nrf2 3. Graphical abstract

Язык: Английский

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Inosine attenuates rotenone‐induced Parkinson's disease in rats by alleviating the imbalance between autophagy and apoptosis

Drug Development Research, Год журнала: 2023, Номер 84(6), С. 1159 - 1174

Опубликована: Май 12, 2023

Growing evidence points to impaired autophagy as one of the major factors implicated in pathophysiology Parkinson's disease (PD). Autophagy is a downstream target adenosine monophosphate-activated protein kinase (AMPK). Inosine has already demonstrated neuroprotective effect against neuronal loss neurodegenerative diseases, mainly due its anti-inflammatory and antioxidant properties. We, herein, aimed at investigating effects inosine rotenone-induced PD rats focus on activation AMPK-mediated autophagy. successfully increased p-AMPK/AMPK ratio improved their motor performance muscular co-ordination (assessed by rotarod, open field, grip strength tests, well manual gait analysis). Furthermore, was able mitigate histopathological alterations restore tyrosine hydroxylase immunoreactivity rats' substantia nigra. Inosine-induced AMPK resulted an enhancement, striatal Unc-S1-like kinase1 beclin-1 expression, also increment light chain 3II 3I ratio, along with decline mammalian rapamycin p62 expressions. The inosine-induced stimulation attenuated apoptosis promoted activity. Unsurprisingly, these were antagonized preadministration dorsomorphin (an inhibitor). In conclusion, exerted via through restoration imbalance between apoptosis. These findings support potential application treatment.

Язык: Английский

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Glucagon-like peptide 1 receptor activation: anti-inflammatory effects in the brain

Neural Regeneration Research, Год журнала: 2023, Номер 19(8), С. 1671 - 1677

Опубликована: Дек. 11, 2023

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and key in treating metabolic diseases such as diabetes obesity. Glucagon-like exerts its by activating membrane receptor identified many tissues, including different brain regions. activates several signaling pathways related to neuroprotection, like the support of cell growth/survival, enhancement promotion synapse formation, autophagy, inhibition secretion proinflammatory cytokines, microglial activation, apoptosis during neural morphogenesis. glial cells, astrocytes microglia, maintain homeostasis defense against pathogens central nervous system. After insult, microglia are first cells respond, followed reactive astrocytosis. These activated produce mediators cytokines or chemokines react insult. Furthermore, under these circumstances, can become chronically inflammatory losing their homeostatic molecular signature and, consequently, functions diseases. Several processes promote development neurological disorders influence pathological evolution: formation protein aggregates, accumulation abnormally modified cellular constituents, release injured neurons synapses molecules dampen function, critical importance, dysregulation control mechanisms. agonist emerges tool brain-related pathologies, restoring conditions, modulating activity, decreasing response. This review summarizes recent advances linked anti-inflammatory properties activation multiple sclerosis, Alzheimer's disease, Parkinson's vascular dementia, chronic migraine.

Язык: Английский

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Semaglutide ameliorated autism-like behaviors and DNA repair efficiency in male BTBR mice by recovering DNA repair gene expression

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2024, Номер 135, С. 111091 - 111091

Опубликована: Июль 18, 2024

Язык: Английский

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