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1.
Neurochem Res ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38987448

RESUMO

Luteolin is an essential natural polyphenol found in a variety of plants. Numerous studies have supported its protective role in neurodegenerative diseases, yet the research for its therapeutic utility in D-galactose (D-gal)-induced brain ageing is still lacking. In this study, the potential neuroprotective impact of luteolin against D-gal-induced brain ageing was explored. Forty rats were randomly divided into four groups: control, luteolin, D-gal, and luteolin-administered D-gal groups. All groups were subjected to behavioural, cholinergic function, and hippocampal mitochondrial respiration assessments. Hippocampal oxidative, neuro-inflammatory, senescence and apoptotic indicators were detected. Gene expressions of SIRT1, BDNF, and RAGE were assessed. Hippocampal histopathological studies, along with GFAP and Ki67 immunoreactivity, were performed. Our results demonstrated that luteolin effectively alleviated D-gal-induced cognitive impairment and reversed cholinergic abnormalities. Furthermore, luteolin administration substantially mitigated hippocampus oxidative stress, mitochondrial dysfunction, neuro-inflammation, and senescence triggered by D-gal. Additionally, luteolin treatment considerably attenuated neuronal apoptosis and upregulated hippocampal SIRT1 mRNA expression. In conclusion, our findings revealed that luteolin administration attenuated D-gal-evoked brain senescence, improving mitochondrial function and enhancing hippocampal neuroregeneration in an ageing rat model through its antioxidant, senolytic, anti-inflammatory, and anti-apoptotic impacts, possibly due to upregulation of SIRT1. Luteolin could be a promising therapeutic modality for brain aging-associated abnormalities.

2.
Int J Mol Sci ; 24(11)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37298433

RESUMO

Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure and death. It has no definite treatment. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has protective potential in PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate the ameliorative effect of EMPA against bleomycin (BLM)-induced PF and the potential mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA treated, and EMPA+BLM treated. EMPA significantly improved the histopathological injuries illustrated by both hematoxylin and eosin and Masson's trichrome-stained lung tissue sections, as confirmed by electron microscopic examination. It significantly reduced the lung index, hydroxyproline content, and transforming growth factor ß1 levels in the BLM rat model. It had an anti-inflammatory effect, as evidenced by a decrease in the inflammatory cytokines' tumor necrosis factor alpha and high mobility group box 1, inflammatory cell infiltration into the bronchoalveolar lavage fluid, and the CD68 immunoreaction. Furthermore, EMPA mitigated oxidative stress, DNA fragmentation, ferroptosis, and endoplasmic reticulum stress, as evidenced by the up-regulation of nuclear factor erythroid 2-related factor expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, and a decrease in C/EBP homologous protein levels. This protective potential could be explained on the basis of autophagy induction via up-regulating lung sestrin2 expression and the LC3 II immunoreaction observed in this study. Our findings indicated that EMPA protected against BLM-induced PF-associated cellular stress by enhancing autophagy and modulating sestrin2/adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling.


Assuntos
Ferroptose , Fibrose Pulmonar , Ratos , Masculino , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Bleomicina/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Wistar , Pulmão/patologia
3.
Chem Biol Interact ; 306: 47-53, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30974099

RESUMO

Necroptosis is suggested to have an important role in the pathogenesis of rhabdomyolysis induced acute kidney injury (AKI). In this study, the renoprotective effect of diacerein on glycerol-induced AKI was investigated. Twenty four male albino rats were included in this study and divided into four groups: (group I) saline control group, (group II) glycerol-treated group, (groups III&IV) diacerein + glycerol -treated groups (25 and 50 mg/kg/day) respectively. Renal malondialdehyde (MDA) level in addition to catalase and heme oxygenase (HO) activities were estimated. Comet assay and histopathological changes were evaluated. The levels of pro-apoptotic Bcl-2-associated X (Bax) protein, tumor necrosis factor alpha (TNF-α) and receptor-interacting serine/threonine-protein kinases 3 (RIPK3) were measured by ELISA. RIPK3 and mixed lineage kinase domain-like pseudokinase (MLKL) mRNA expression were assessed by real time PCR. Glycerol treatment caused significant renal histological abnormalities and functional impairment (increased urea and creatinine). Increased levels of renal MDA with concomitant decrease in renal catalase activity and significant DNA damage in comet assay were observed. High expression of RIPK3 and MLKL in the glycerol-treated group with marked elevation of Bax, TNF-α and RIPK3 levels and HO-1 activity were also documented. Diacerein treatment dependently attenuated glycerol induced structural and functional changes in kidney and significantly elicit reduction of renal tissue oxidative damage whereas it decreased renal expression of RIPK3 and MLKL, and decreased Bax, TNF-α and RIPK3 levels and HO-1 activity. CONCLUSION: These results demonstrated that diacerein might have potential application in the amelioration of AKI via its anti-oxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic effects.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antraquinonas/farmacologia , Apoptose/efeitos dos fármacos , Glicerol/farmacologia , Inflamação/prevenção & controle , Necrose/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Dano ao DNA/efeitos dos fármacos , Glicerol/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Necrose/induzido quimicamente , Necrose/patologia , Ratos , Ratos Wistar
4.
J Biochem Mol Toxicol ; : e22231, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30276927

RESUMO

The aim of this study was to investigate the protective effect of montelukast (MTK) against prednisolone-induced hepatic injury in rats. Twenty-eight male albino rats were categorized into four equal groups. Group I served as the control group; group II: rats orally received prednisolone (5 mg·kg-1 ·d-1 ) for 30 days; groups III and IV: rats orally received MTK at 10 and 20 mg·kg-1 ·d-1 , respectively, simultaneously with prednisolone for 30 days. Serum liver enzymes, hepatic mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic markers were evaluated, and the results were confirmed by histopathological examination. MTK showed significant hepatic protection evidenced by alleviated histological lesion and improvement of mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic changes induced by prednisolone, with more profound protection in higher MTK dose (20 mg·kg-1 ). In view of these findings, we can conclude that MTK may have hepatoprotective potential, beyond its therapeutic value for asthmatic patients during their course of corticosteroid therapy.

5.
Can J Physiol Pharmacol ; 96(11): 1161-1170, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30011378

RESUMO

The protective effect of N-acetylcysteine (NAC) and genistein (GEN) on an experimental model of indomethacin (IND)-induced gastric injury was investigated. A total of 50 male rats were divided into 5 groups: (1) control, (2) IND, (3) NAC pretreated, (4) GEN pretreated, and (5) NAC+GEN pretreated. Rats in groups 3-5 were orally administered NAC (500 mg/kg), GEN (10 mg/kg), or both, respectively, once daily for 7 days before the induction of gastric injury by IND (50 mg/kg). The stomach was removed for biochemical analysis and histopathological examination. Pretreatment with NAC, GEN, or both significantly improved ulcer indices and increased nitric oxide level and superoxide dismutase activity. They also significantly decreased malondialdehyde, tumour necrosis factor α levels, and myeloperoxidase activity, and downregulated matrix metalloproteinase 9 (MMP-9) gene expression compared to the IND group. NAC alone ameliorated IND-induced apoptosis, whereas GEN only significantly increased prostaglandin E2 level. Further, coadministration of both resulted in a significantly better gastroprotective effect versus solo administration. Coadministration of NAC and GEN has an additive gastroprotective effect in IND-induced gastric injury, which may be through interaction of their potential cytoprotective, antioxidant, anti-inflammatory, and antiapoptotic mechanisms together with regulation of MMP-9 expression.


Assuntos
Acetilcisteína/farmacologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/farmacologia , Genisteína/farmacologia , Indometacina/efeitos adversos , Úlcera Gástrica/prevenção & controle , Acetilcisteína/uso terapêutico , Animais , Antiulcerosos/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Genisteína/uso terapêutico , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
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