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1.
Clin Exp Nephrol ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935212

ABSTRACT

BACKGROUND: Renal ischemia-reperfusion injury (RIRI) is a critical phenomenon that compromises renal function and is the most serious health concern related to acute kidney injury (AKI). Pioglitazone (Pio) is a known agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). PPAR-γ is a nuclear receptor that regulates genes involved in inflammation, metabolism, and cellular differentiation. Activation of PPAR-γ is associated with antiinflammatory and antioxidant effects, which are relevant to the pathophysiology of RIRI. This study aimed to investigate the protective effects of Pio in RIRI, focusing on oxidative stress and inflammation. METHODS: We conducted a comprehensive literature search using electronic databases, including PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar. RESULTS: The results of this study demonstrated that Pio has antioxidant, anti-inflammatory, and anti-apoptotic activities that counteract the consequences of RIRI. The study also discussed the underlying mechanisms, including the modulation of various pathways such as TNF-α, NF-κB signaling systems, STAT3 pathway, KIM-1 and NGAL pathways, AMPK phosphorylation, and autophagy flux. Additionally, the study presented a summary of various animal studies that support the potential protective effects of Pio in RIRI. CONCLUSION: Our findings suggest that Pio could protect the kidneys from RIRI by improving antioxidant capacity and decreasing inflammation. Therefore, these findings support the potential of Pio as a therapeutic strategy for preventing RIRI in different clinical conditions.

2.
Fundam Clin Pharmacol ; 38(2): 225-237, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37753585

ABSTRACT

BACKGROUND: Despite several hundred clinical trials of drugs that initially showed promise, there has been limited clinical improvement in Alzheimer's disease (AD). This may be attributed to the existence of at least 25 abnormal cellular pathways that underlie the disease. It is improbable for a single drug to address all or most of these pathways, thus even drugs that show promise when administered alone are unlikely to produce significant results. According to previous studies, eight drugs, namely, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, have been found to target multiple pathways that are involved in the development of AD. Among these drugs, riluzole is currently indicated for the treatment of medical conditions in both adult patients and children and has gained increased attention from scientists due to its potential in the excitotoxic hypothesis of neurodegenerative diseases. OBJECTIVE: The aim of this study was to investigate the effects of drugs on AD based on cellular and molecular mechanisms. METHODS: The literature search for this study utilized the Scopus, ScienceDirect, PubMed, and Google Scholar databases to identify relevant articles. RESULTS: Riluzole exerts its effects in AD through diverse pathways including the inhibition of voltage-dependent sodium and calcium channels, blocking AMPA and NMDA receptors and inhibiting the release of glutamic acid release and stimulation of EAAT1-EAAT2. CONCLUSION: In this review article, we aimed to review the neuroprotective properties of riluzole, a glutamate modulator, in AD, which could benefit patients with the disease.


Subject(s)
Alzheimer Disease , Neuroprotective Agents , Child , Humans , Riluzole/pharmacology , Riluzole/therapeutic use , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Amino Acid Antagonists/therapeutic use , Memantine/pharmacology , Memantine/therapeutic use
3.
Neuroscience ; 527: 52-63, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37499782

ABSTRACT

Spinal cord injury (SCI) following trauma is a devastating neurological event that can lead to loss of sensory and motor functions. However, the most effective measures to prevent the spread of damage are treatment measures in the early stages. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with epigallocatechin-3-gallate (EGCG) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley rats were randomly planned into five equal groups (n = 18). In addition to sham group that only underwent laminectomy, SCI rats were allocated into 4 groups as follows: control group; HBO group; EGCG group; and HBO + EGCG group. Tissue samples at the lesion site were obtained for stereological, immunohistochemical, biochemical, and molecular evaluation. In addition, behavioral tests were performed to assess of neurological functions. The finding indicated that the stereological parameters, antioxidant factors (CAT, GSH, and SOD), IL-10 gene expression levels and neurological functions were considerably increased in the treatment groups in comparison with control group, and these changes were more obvious in the HBO + EGCG group (P < 0.05). On the other hand, we observed that the density of apoptotic cells and gliosis, the biochemical levels of MDA and the expression levels of inflammatory genes (TNF-α and IL-1ß) in the treatment groups, especially the HBO + EGCG group, were considerably reduced in comparison with control group (P < 0.05). We conclude that co-administration of HBO and EGCG has a synergistic neuroprotective effects in animals undergoing SCI.


Subject(s)
Hyperbaric Oxygenation , Spinal Cord Injuries , Rats , Male , Animals , Rats, Sprague-Dawley , Spinal Cord/metabolism , Spinal Cord Injuries/metabolism , Oxygen/metabolism
4.
Wiad Lek ; 76(2): 360-369, 2023.
Article in English | MEDLINE | ID: mdl-37010174

ABSTRACT

OBJECTIVE: The aim: The current study was designed for evaluation the effect of oral magnesium l-lactate supplementation on blood pressure and corrected QT interval in a sample of Iraqi women. PATIENTS AND METHODS: Materials and methods: In this interventional prospective randomized trial, 58 female patients diagnosed with MetS according to the International Diabetic Federation (IDF) criteria and were randomly allocated to receive either placebo or magnesium l-lactate 84 mg, twice daily. RESULTS: Results: O#ce blood pressure showed a signi$cant drop in systolic blood pressure (SBP) (P<0.05), non-significant decline in diastolic blood pressure (DBP), heart rate (HR), and pulse pressure (PP) (P>0.05), while ambulatory blood pressure monitoring (ABPM) recorded a signi$cant reduction in HR in patients on magnesium supplement. Also, there was a signi$cant decline in the SBP (P<0.05) and non-signi$cant decline in DBP and PP (P>0.05) in patients with masked hypertension on Mg supplement. The changes in corrected QT- interval had no signi$cant e"ect within Mg group (P>0.05). CONCLUSION: Conclusions: From above results, one can conclude that oral Mg l-lactate supplement can improve, to a certain extent, blood pressure of women with MetS. Further studies in this aspect may be required.


Subject(s)
Hypertension , Metabolic Syndrome , Humans , Female , Blood Pressure/physiology , Magnesium/therapeutic use , Blood Pressure Monitoring, Ambulatory/methods , Lactic Acid/therapeutic use , Prospective Studies , Iraq
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