GSK‐3β/Notch‐1 Activation Promotes Radiation‐Induced Renal Damage: The Role of Gallic Acid in Mitigation of Nephrotoxicity DOI
Doaa H. Abdel‐Naby, Marwa M. El‐Sheikh,

Sahar S. Abd El‐Rahman

et al.

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(11), P. 4871 - 4883

Published: June 18, 2024

ABSTRACT Despite the therapeutic advances in treating malignancies, efficient radiotherapeutic approaches with deprived adverse reactions still represent a potential clinical inquiry. The current study aims to elucidate role of gallic acid (GA) modifying hazardous renal cytotoxicity induced by acute exposure radiation. MTT test was used evaluate viability Vero cells exposed 2 Gy gamma radiation or without incubation GA. In an vivo model, male Wistar rats were divided into four experimental groups ( n = 6): Control, Irradiated (IRR, 5 Gy), GA (100 mg/kg, i.p.) + IRR, and Glycogen synthase kinase inhibitor (GSKI, 3 IRR. Based on toxicity assay, from 0 up μM dosages did not demonstrate any cells. optimal dose that could protect μM. Furthermore, exerted protective effect tissue as indicated corrected functions, decreased LDH level serum, balanced oxidative status, which is contents NOx TBARS significant increase reduced GSH. These outcomes inferred upregulation nuclear factor erythroid 2‐related (Nrf2) expression. overall molecular impact damaging may be explained upstream AKT activity its downstream targets GSK‐3β/Notch‐1. Here, we concluded anticipated reaction course protected daily administration

Language: Английский

Repurposing Secukinumab and Dapagliflozin as Candidate Therapies to Mitigate the Renal Toxicity of Sunitinib in Rats Through Suppressing IL‐17‐Mediated Pyroptosis and Promoting Autophagy DOI Open Access
Rania A. Elrashidy,

Hoda E. Mohamad,

Sara M. Abdel Aal

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: March 1, 2025

Sunitinib (SUN) is a chemotherapeutic agent showing renal toxicity that limits its clinical applications. The present research aimed to clarify the potential ameliorative effects of secukinumab (SEC) and dapagliflozin (DAPA) against SUN-induced underpinning molecular mechanisms. For this purpose, adult Wistar albino rats were received SUN (25 mg/kg 3 times/week, po) co-treated with SEC (3 mg/kg/every 2 weeks, subcutaneously) or DAPA (10 mg/kg/day, for 4 weeks compared age-matched control group (CON). Markers kidney functions assessed in serum samples. Kidneys harvested biochemical histological examination. Compared CON group, SUN-treated displayed signs dysfunction along changes ameliorated by DAPA. Both drugs significantly lowered levels IL-17, but exerted more inhibitory effect than Additionally, SUN-subjected showed significant increases expression NLRP3 inflammasome other inflammatory mediators including IL-1β, END-1, MCP-1. This was associated marked decline beclin-1. Co-treatment suppressed NLRP3-induced inflammation while enhanced beclin-1-mediated autophagy. modulatory on beclin-1 superior SEC. Moreover, both similarly attenuated cleaved caspase-3 interstitial fibrosis tissue rats. Collectively, these findings may repurpose as candidate therapies alleviate rescue functionality cancer cases.

Language: Английский

Citations

0
Oleuropein mitigates acetaminophen overdose-induced kidney injury in male rats by enhancing antioxidant defense and suppressing inflammatory and apoptotic pathways DOI

Zahra Sedghi,

Ayat Kaeidi, Jalal Hassanshahi

et al.

Drug and Chemical Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: March 26, 2025

Acetaminophen (APAP) is a well-known analgesic, and antipyretic drug its overdose or chronic consumption can lead to kidney damage. Oleuropein (OLE) exhibits various pharmacological properties. This study aimed determine the possible therapeutic benefits of OLE in improving APAP-induced injury. In this experimental study, 36 male Wistar rats were assigned six groups (n = 6). The initially received single dose APAP (500 mg/kg) then 1 hour later treated with at 50, 100, 200 mg/kg depending on their groups. 24 hours after treatment OLE, indicators including biochemical tests, histopathological changes, oxidative stress markers, anti-apoptotic anti-inflammatory parameters investigated renal tissue. (100 significantly decreased serum creatinine, caspase-3, tissue damage score (P < 0.05), malondialdehyde (MDA) 0.01), increased superoxide dismutase (SOD) total antioxidant capacity (TAC) 0.05) + 100 group versus group. Additionally, (200 reduced blood urea nitrogen (BUN), NF-κB, p53, Bax (p TNF-α, MDA, Bax: Bcl-2 ratio 0.001) Also, enhanced glutathione peroxidase (GPx), SOD, TAC 0.01) contrasted However, 50 didn't alter measured parameters. These findings demonstrate that could attenuate acetaminophen-induced injury through anti-oxidant, anti-inflammatory, anti-apoptosis

Language: Английский

Citations

0
Efficient recovery of antioxidants from olive leaves through green solvent extraction and enzymatic hydrolysis: Experimental evaluation and COSMO-RS analysis DOI Creative Commons
Andrea Sánchez-Monedero, Rubén Santiago, Ismael Díaz

et al.

Journal of Molecular Liquids, Journal Year: 2024, Volume and Issue: 408, P. 125368 - 125368

Published: June 26, 2024

The present study focuses on the valorization of olive leaves (Olea europaea L.) through recovery high-value antioxidants using green solvents (i.e., bio-based (BioS) and natural eutectic (NAES)) while evaluating implementation an enzymatic hydrolysis step for biomass pretreatment. Overall, 12 BioS including water, alcohols, ethers, esters, terpenes, 7 NAES composed choline chloride, proline, betaine combined with polyols, were studied as solid–liquid extraction from leaves. generally performed better than BioS, Proline:1,2-butanediol [1:4] being most efficient, yielding 75 mg total polyphenols/g dried sample in non-pretreated extract. As composition, 95 % extract was constituted by oleuropein, while, average, 65 pretreated found to be a mixture hydroxytyrosol oleuropein. In all cases, polyphenols extracted determined high-performance liquid chromatography. Finally, experimental results analyzed COSMO-RS methodology, obtaining reliable solubility trends target proposed solvents, explaining thermodynamic interactions systems terms molecular behavior. This work can serve guideline develop flexible biorefinery schemes production oleuropein based different approaches, silico tools providing further insights into role novel olive-derived processes.

Language: Английский

Citations

1
GSK‐3β/Notch‐1 Activation Promotes Radiation‐Induced Renal Damage: The Role of Gallic Acid in Mitigation of Nephrotoxicity DOI
Doaa H. Abdel‐Naby, Marwa M. El‐Sheikh,

Sahar S. Abd El‐Rahman

et al.

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(11), P. 4871 - 4883

Published: June 18, 2024

ABSTRACT Despite the therapeutic advances in treating malignancies, efficient radiotherapeutic approaches with deprived adverse reactions still represent a potential clinical inquiry. The current study aims to elucidate role of gallic acid (GA) modifying hazardous renal cytotoxicity induced by acute exposure radiation. MTT test was used evaluate viability Vero cells exposed 2 Gy gamma radiation or without incubation GA. In an vivo model, male Wistar rats were divided into four experimental groups ( n = 6): Control, Irradiated (IRR, 5 Gy), GA (100 mg/kg, i.p.) + IRR, and Glycogen synthase kinase inhibitor (GSKI, 3 IRR. Based on toxicity assay, from 0 up μM dosages did not demonstrate any cells. optimal dose that could protect μM. Furthermore, exerted protective effect tissue as indicated corrected functions, decreased LDH level serum, balanced oxidative status, which is contents NOx TBARS significant increase reduced GSH. These outcomes inferred upregulation nuclear factor erythroid 2‐related (Nrf2) expression. overall molecular impact damaging may be explained upstream AKT activity its downstream targets GSK‐3β/Notch‐1. Here, we concluded anticipated reaction course protected daily administration

Language: Английский

Citations

0