Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway DOI Creative Commons
Samar Ibrahim,

Eman H. Yousef,

Ahmed M. El‐Dessouki

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Although gemcitabine is a primary chemotherapy for pancreatic cancer, its effectiveness limited by chemoresistance and nephrotoxicity, posing significant clinical challenges. Therefore, the development of novel therapeutic approaches to prevent malignancy remains crucial. This study aimed investigate potential melatonin in enhancing gemcitabine’s anticancer efficacy while mitigating nephrotoxic effects through modulation Keap1/p62 pathway. A cancer xenograft model was established rats, which received either (50 mg/kg, I.P.), or their combination three times per week 2 weeks. Our findings demonstrate that potentiates cancer-suppressing via Kelch-like-ECH associated protein-1 (Keap1)/p62 pathway, resulting reduced fibrosis, oxidative stress, inflammatory markers. Additionally, significantly mitigated gemcitabine-induced nephrotoxicity. These results suggest may serve as an adjuvant therapy treatment, reducing adverse effects.

Language: Английский

Advances in micro- and nano- delivery systems for increasing the stability, bioavailability and bioactivity of coenzyme Q 10 DOI

Ruoxuan Hong,

Yahong Han, Shuai Chen

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: Jan. 16, 2025

Coenzyme Q10 acts as a liposoluble quinone compound in mitochondrial oxidative phosphorylation, serving an electron carrier and protecting the cell membrane structure antioxidant. has notable health benefits, including anti-aging, anti-inflammatory, prevention of cardiovascular diseases, assistance cancer treatment. However, its poor water solubility, unstable chemical properties, low bioavailability significantly limit application. This article reviewed design development processes various delivery systems for coenzyme Q10, discussing advantages disadvantages different their improvement strategies, improvements stability accessibility emulsions, achieving higher penetration rates oleogels, reducing use toxic substances production process liposomes. The mechanisms behind Q10's were analyzed, bioactivity research prospects also discussed. In summary, this review offered valuable insights into application which may provide reference pharmaceuticals, cosmetics, products, other industries future.

Language: Английский

Citations

0
Cadmium exposure induced spleen inflammation by activating the MAPK/NF-κB/ NLRP3 signaling pathway and the intervention effect of Astilbin DOI
Tiezhu Chen, Tianyu Han,

Yusong Miao

et al.

Veterinary Immunology and Immunopathology, Journal Year: 2025, Volume and Issue: 281, P. 110889 - 110889

Published: Jan. 31, 2025

Language: Английский

Citations

0
Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways DOI Creative Commons
Ahmed M. El‐Dessouki,

Mohamed E. Kaml,

Mohammed F. EL-Yamany

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Abstract This research investigated the hepatoprotective effects of esomeprazole (ESOM) and canagliflozin (CANA) against methotrexate-induced liver toxicity, focusing on AMPK modulation its regulation MAPK/JNK/ERK, JAK1/STAT3, PI3K/Akt pathways. Fifty male Wistar rats were divided into five groups: control, MTX, three pretreatment groups receiving ESOM (30 mg/kg), CANA or their combination. administered for 8 days before 1 day after a single MTX injection (20 mg/kg, intraperitoneally) 9 to induce hepatotoxicity. Liver injury, oxidative stress, inflammation, apoptosis assessed using biochemical, histopathological, immunohistochemical, qRT-PCR, western blot analyses. Data analyzed by one-way analysis variance (ANOVA) Tukey’s post hoc test, with significance at p < 0.05. Results presented as mean ± standard error (SE). Rats that received showed significant damage, marked elevated ALT, AST, MDA, MPO, iNOS, TNF-α, IL-6, IL-1β levels ( 0.01) decreased antioxidant enzymes (HO-1, Nrf2, GSH). Immunohistochemistry revealed increased NF-kB p65 caspase-9 expression 0.01), correlating histopathological changes. Pretreatment reduced enzyme levels, improved histology, restored balance, inhibited inflammatory pathways via p38MAPK/NF-kB JAK1/STAT3 0.01). Moreover, preserved activity prevented caspase-dependent Additionally, combination treatment synergistic effects, demonstrated improvements in all measured parameters. These findings suggested had potential therapeutic agents alleviating MTX-induced hepatotoxicity warranted further investigation future research.

Language: Английский

Citations

0
Regulation of pyroptosis by NF-κB signaling DOI Creative Commons
Ling Yang, Yan Zhang,

Zhuodong Chai

et al.

Frontiers in Cell Death, Journal Year: 2025, Volume and Issue: 3

Published: Jan. 7, 2025

Pyroptosis is a form of proinflammatory cell death characterized by inflammasome activation, pore formation, and the release pro-inflammatory cytokines such as interleukin-1β (IL-1β) IL-18 upon rupture. Nuclear factor-κB (NF-κB), prototypical transcription factor, plays critical role in immune system regulation. Recent research highlights multifaceted roles NF-κB signaling pyroptosis. Various immunologically relevant ligands their receptors can activate pathway to promote pyroptosis, with Toll-like (TLRs), IL-1 (IL-1Rs), TNF (TNFRs) being most prominent. regulates key components inflammasomes involved particularly NLRP3 inflammasome. studies also indicate that modulates activation NLRC4 AIM2 through distinct pathways diverse inflammatory conditions, acute lung injury neuroinflammation. Additionally, mediates production cytokines, including IL-1β, IL-33, TNF-α, which further regulate This review examines recent advances understanding regulating pyroptosis during infection inflammation.

Language: Английский

Citations

0
Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway DOI Creative Commons
Samar Ibrahim,

Eman H. Yousef,

Ahmed M. El‐Dessouki

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Although gemcitabine is a primary chemotherapy for pancreatic cancer, its effectiveness limited by chemoresistance and nephrotoxicity, posing significant clinical challenges. Therefore, the development of novel therapeutic approaches to prevent malignancy remains crucial. This study aimed investigate potential melatonin in enhancing gemcitabine’s anticancer efficacy while mitigating nephrotoxic effects through modulation Keap1/p62 pathway. A cancer xenograft model was established rats, which received either (50 mg/kg, I.P.), or their combination three times per week 2 weeks. Our findings demonstrate that potentiates cancer-suppressing via Kelch-like-ECH associated protein-1 (Keap1)/p62 pathway, resulting reduced fibrosis, oxidative stress, inflammatory markers. Additionally, significantly mitigated gemcitabine-induced nephrotoxicity. These results suggest may serve as an adjuvant therapy treatment, reducing adverse effects.

Language: Английский

Citations

0