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Naraki, Karim, Ghasemzadeh Rahbardar, Mahboobeh, Razavi, Bibi Marjan, Aminifard, Tahereh, Khajavirad, Abolfazl, Hosseinzadeh, Hossein. (1404). Examining the role of trans-sodium crocetinate in alleviating colistin-induced cytotoxicity through apoptosis and autophagy pathways on HEK-293 cells. , (), -. doi: 10.22038/ijbms.2025.82430.17820
Karim Naraki; Mahboobeh Ghasemzadeh Rahbardar; Bibi Marjan Razavi; Tahereh Aminifard; Abolfazl Khajavirad; Hossein Hosseinzadeh. "Examining the role of trans-sodium crocetinate in alleviating colistin-induced cytotoxicity through apoptosis and autophagy pathways on HEK-293 cells". , , , 1404, -. doi: 10.22038/ijbms.2025.82430.17820
Naraki, Karim, Ghasemzadeh Rahbardar, Mahboobeh, Razavi, Bibi Marjan, Aminifard, Tahereh, Khajavirad, Abolfazl, Hosseinzadeh, Hossein. (1404). 'Examining the role of trans-sodium crocetinate in alleviating colistin-induced cytotoxicity through apoptosis and autophagy pathways on HEK-293 cells', , (), pp. -. doi: 10.22038/ijbms.2025.82430.17820
Naraki, Karim, Ghasemzadeh Rahbardar, Mahboobeh, Razavi, Bibi Marjan, Aminifard, Tahereh, Khajavirad, Abolfazl, Hosseinzadeh, Hossein. Examining the role of trans-sodium crocetinate in alleviating colistin-induced cytotoxicity through apoptosis and autophagy pathways on HEK-293 cells. , 1404; (): -. doi: 10.22038/ijbms.2025.82430.17820

Examining the role of trans-sodium crocetinate in alleviating colistin-induced cytotoxicity through apoptosis and autophagy pathways on HEK-293 cells

Iranian Journal of Basic Medical Sciences
مقالات آماده انتشار، پذیرفته شده، انتشار آنلاین از تاریخ 16 تیر 1404    اصل مقاله (615.18 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2025.82430.17820
نویسندگان
Karim Naraki1، 2؛ Mahboobeh Ghasemzadeh Rahbardar2؛ Bibi Marjan Razavi3، 1؛ Tahereh Aminifard1؛ Abolfazl Khajavirad4، 5؛ Hossein Hosseinzadeh* 2، 6
1Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
2Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
3Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
4Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5Applied biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
6Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran 2 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran 3 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran 4 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 5 Applied biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
چکیده
Objective(s): Colistin is a crucial antibiotic for multidrug-resistant Gram-negative bacterial infections, but its nephrotoxicity limits clinical use. Trans sodium crocetinate (TSC), a synthetic crocetin derivative, exhibits anti-oxidative, antiapoptotic, and renal-protective effects. This study investigated whether TSC could alleviate colistin-induced cytotoxicity in HEK-293 cells, a human renal epithelial model.
Materials and Methods: HEK-293 cells were pretreated with varying TSC concentrations for 24 hr, followed by 200 µM colistin for another 24 hr. Cell viability was measured via MTT assay, and reactive oxygen species (ROS) levels were quantified using DCFH-DA fluorescence. Apoptotic markers (Bax, Bcl-2, caspase-3) and autophagy-related proteins (LC3, Beclin-1) were analyzed by western blotting.
Results: Colistin reduced HEK-293 cell viability by 50%, increased ROS by 43%, and elevated autophagy markers (LC3, Beclin-1) by 50%. The Bax/Bcl-2 ratio rose by 50%, and cleaved caspase-3 increased by 33% compared to controls. However, TSC pretreatment significantly attenuated these effects: viability improved by 35%, ROS decreased by 50%, and the Bax/Bcl-2 ratio dropped by 50%. Additionally, TSC reduced Bax (40%), cleaved caspase-3 (55%), LC3 (35%), and Beclin-1 (45%) levels compared to colistin-only treatment.
Conclusion: These findings suggest that TSC protects HEK-293 cells from colistin-induced toxicity by reducing oxidative stress, suppressing apoptosis, and modulating autophagy. Thus, TSC may serve as a potential adjunct therapy to mitigate colistin-associated nephrotoxicity.
کلیدواژه‌ها
Anti-oxidants؛ Apoptosis markers؛ Autophagy markers؛ Colistin؛ HEK-293؛ Nephrotoxicity؛ Reactive oxygen species؛ Saffron
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