Ameliorative Effect of N-Acetylcysteine Against 5-Fluorouracil-Induced Cardiotoxicity via Targeting TLR4/NF-κB and Nrf2/HO-1 Pathways DOI Creative Commons
Omer Abdelbagi, Medhat Taha,

Abdullah G. Al-Kushi

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 335 - 335

Published: Feb. 14, 2025

Background and Objectives: 5-Fluorouracil (5-FU) is a widely prescribed effective chemotherapeutic drug, but its cardiotoxic side effects pose significant challenge to use. Identifying protective agent that does not affect anticancer efficacy essential. Our study aimed investigate the cardioprotective effect of N-acetyl cysteine (NAC) against 5-FU-induced cardiac injury elucidate underlying mechanisms. Materials Methods: This included four experimental groups, each with eight rats (n = 8): Group I (control group), II (NAC III (5-FU IV (combined group 5-FU+NAC). Cardiac enzymes, oxidative stress, inflammatory, apoptotic markers were investigated, sections from different groups histologically examined. Results: Co-treatment 5-FU NAC resulted in significantly lower levels enzymes (alanine transaminase (ALT) by 62.1%, aspartate (AST) 73.6%, lactate dehydrogenase (LDH) 55.8%, creatine kinase (CK) 57.3%) compared group, along marked improvements heart tissue histology. Additionally, enhanced activity antioxidant (superoxide dismutase (SOD) 295.6%, catalase (CAT) 181%, glutathione peroxidase (GPx) 320.9%) while decreasing malondialdehyde (MDA) 51.1%, marker membranous lipid peroxidation. might be due upregulation nuclear factor erythroid-2-related 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway at gene protein levels. The combined treatment decreased expression toll-like receptor 4 (TLR4)/nuclear kappa-light-chain-enhancer activated B-cell (NF-κB) pathway. Furthermore, it downregulated inflammatory markers, including tumor necrosis factor-alpha (TNF-α) 29.9%, interleukin-1 beta (IL-1β) 21.9%, interleukin-6 (IL-6) 49.3%. Moreover, upregulated antiapoptotic lymphoma (Bcl-2) 269% indicators Bcl-2-associated x (Bax) 57.9% caspase-3 30.6% group. Conclusions: confirmed prevented through antioxidant, anti-inflammatory, properties, suggesting potential application as an adjuvant therapy chemotherapy alleviate cardiotoxicity.

Language: Английский

Alterations in Autophagic Function and Endoplasmic Reticulum Stress Markers in the Peripheral Blood Mononuclear Cells of Patients on Hemodialysis DOI Open Access
Wen‐Chih Liu,

Ming-Yin Wu,

Paik‐Seong Lim

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 447 - 447

Published: Jan. 7, 2025

Oxidative stress, endoplasmic reticulum (ER) and alterations in autophagy activity have been described as prominent factors mediating many pathological processes chronic kidney disease (CKD). The accumulation of misfolded proteins the ER may stimulate unfolded protein response (UPR). interplay between UPR hemodialysis (HD) patients remains unclear. aim present study was to explore associations serum oxidative stress markers, activity, markers peripheral blood mononuclear cells (PBMCs) on HD. Autophagy stress-related expression levels PBMCs were measured using western blotting. redox state human albumin via high-performance liquid chromatography. Levels microtubule associated light chain 3 (LC3)-II, BECLIN1, p62/SQSTM1 significantly increased HD compared healthy subjects. also displayed augmented glucose-regulated 78 kDa (GRP78), phosphorylated eukaryotic translation initiation factor 2, subunit 1 alpha (p-eIF2α), activating transcription 6 (ATF6) (p < 0.05). Additionally, nuclear erythroid 2 (NF-E2)-related (NRF2) elevated patients, those Correlation analysis showed that status correlated with p62 level PBMCs. Compared controls, we found autophagosome formation patients. Increased observed Furthermore, positively NRF2, well a reduced form (human mercaptalbumin; HMA),

Language: Английский

Citations

0
Ameliorative Effect of N-Acetylcysteine Against 5-Fluorouracil-Induced Cardiotoxicity via Targeting TLR4/NF-κB and Nrf2/HO-1 Pathways DOI Creative Commons
Omer Abdelbagi, Medhat Taha,

Abdullah G. Al-Kushi

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 335 - 335

Published: Feb. 14, 2025

Background and Objectives: 5-Fluorouracil (5-FU) is a widely prescribed effective chemotherapeutic drug, but its cardiotoxic side effects pose significant challenge to use. Identifying protective agent that does not affect anticancer efficacy essential. Our study aimed investigate the cardioprotective effect of N-acetyl cysteine (NAC) against 5-FU-induced cardiac injury elucidate underlying mechanisms. Materials Methods: This included four experimental groups, each with eight rats (n = 8): Group I (control group), II (NAC III (5-FU IV (combined group 5-FU+NAC). Cardiac enzymes, oxidative stress, inflammatory, apoptotic markers were investigated, sections from different groups histologically examined. Results: Co-treatment 5-FU NAC resulted in significantly lower levels enzymes (alanine transaminase (ALT) by 62.1%, aspartate (AST) 73.6%, lactate dehydrogenase (LDH) 55.8%, creatine kinase (CK) 57.3%) compared group, along marked improvements heart tissue histology. Additionally, enhanced activity antioxidant (superoxide dismutase (SOD) 295.6%, catalase (CAT) 181%, glutathione peroxidase (GPx) 320.9%) while decreasing malondialdehyde (MDA) 51.1%, marker membranous lipid peroxidation. might be due upregulation nuclear factor erythroid-2-related 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway at gene protein levels. The combined treatment decreased expression toll-like receptor 4 (TLR4)/nuclear kappa-light-chain-enhancer activated B-cell (NF-κB) pathway. Furthermore, it downregulated inflammatory markers, including tumor necrosis factor-alpha (TNF-α) 29.9%, interleukin-1 beta (IL-1β) 21.9%, interleukin-6 (IL-6) 49.3%. Moreover, upregulated antiapoptotic lymphoma (Bcl-2) 269% indicators Bcl-2-associated x (Bax) 57.9% caspase-3 30.6% group. Conclusions: confirmed prevented through antioxidant, anti-inflammatory, properties, suggesting potential application as an adjuvant therapy chemotherapy alleviate cardiotoxicity.

Language: Английский

Citations

0