Low Molecular Weight Dextran Sulfate Mitigates Acute Kidney Injury Induced by Renal Ischemia/Reperfusion: Implication of JNK/p38 MAPK and Caspase-3.
- 1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
- 2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
- 3Experimental Surgery and Animal Lab, Prince Naif for Health Research Center (PNHRC), College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11451, Saudi Arabia.
Abstract
Renal ischemia/reperfusion injury (RI/RI) is one of the major causes of acute kidney injury (AKI). Low molecular weight-dextran sulphate (LMW-DS) is a bioactive polysaccharide with anti-inflammatory and cytoprotective properties. This study investigated the nephroprotective potential of LMW-DS against the RI/RI. RI/RI rat model underwent surgery that involved a complete bilateral clamping of renal hila for 30 min, followed by unclamping for 30 min. LMW-DS (5 mg/kg, s.c.) was injected 5 min before unclamping. After 24 h, kidneys were collected for biochemical, histopathological, and immunohistochemical examinations. RI/RI dramatically induced renal deterioration, as reflected by marked elevation in the levels of renal oxidative stress, tumor necrosis factor-α, interleukin-6, and toll-like receptor-4, indicating lipid peroxidation and inflammatory response. Furthermore, RI/RI caused upregulation of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Additionally, morphological alterations and collagen deposition were also detected in kidney tissues. The immunohistochemical analysis revealed a strong positive immunoreaction for p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and caspase-3. Treatment with LMW-DS produced a pronounced amelioration in the altered parameters induced by RI/RI. In conclusion, LMW-DS exerts nephroprotective effects against RI/RI by restoring redox balance, suppressing inflammatory signaling, JNK/p38 MAPK, and caspase-3, highlighting its potential as a therapeutic strategy for renal I/R-induced AKI.
Related
- BD2-selective BRD4 inhibitor ZX29 mitigates myocardial ischemia-reperfusion injury via BRD4-YY1-NCOA4 axis disruption and ferroptosis inhibition.
- Caffeic acid mitigates myocardial fibrosis via suppressing MAPKs/CREB-mediated inflammation in myocardial ischemia-reperfusion injury mice.
- Myocardial Ischemia-Reperfusion Injury: Molecular Mechanisms and Innovative Therapeutic Strategies
- Volatile Anesthetic-Based Combination Strategies Against Ischemia–Reperfusion Injury: Experimental Evidence, Molecular Mechanisms, and Translational Limitations
- Dynamics of cell states and alternative splicing following kidney ischemia-reperfusion injury
BibTeX
@article{alamri2026molecular,
title = {{Low Molecular Weight Dextran Sulfate Mitigates Acute Kidney Injury Induced by Renal Ischemia/Reperfusion: Implication of JNK/p38 MAPK and Caspase-3.}},
author = {Nadrah S Alamri and Ahlam M Alhusaini and Wedad S Sarawi and Hala A Attia and Iman H Hasan and Alia O Alshabanah and Ragad A Alharajeen and Ahmed A Altuwaijri and Faris A Almutairi and Hanaa M Altuwaijri and Dalal A Alkhelb and Sahar S Alotaibi and Abdullah Y Almubarak and Yasser A Alshawakir},
journal = {Antioxidants (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/antiox15101238},
url = {https://europepmc.org/article/MED/42939812},
note = {CC BY},
}
RIS
TY - JOUR
TI - Low Molecular Weight Dextran Sulfate Mitigates Acute Kidney Injury Induced by Renal Ischemia/Reperfusion: Implication of JNK/p38 MAPK and Caspase-3.
AU - Nadrah S Alamri
AU - Ahlam M Alhusaini
AU - Wedad S Sarawi
AU - Hala A Attia
AU - Iman H Hasan
AU - Alia O Alshabanah
AU - Ragad A Alharajeen
AU - Ahmed A Altuwaijri
AU - Faris A Almutairi
AU - Hanaa M Altuwaijri
AU - Dalal A Alkhelb
AU - Sahar S Alotaibi
AU - Abdullah Y Almubarak
AU - Yasser A Alshawakir
PY - 2026
DA - 2026/09/25
JO - Antioxidants (Basel, Switzerland)
DO - 10.3390/antiox15101238
UR - https://europepmc.org/article/MED/42939812
AB - Renal ischemia/reperfusion injury (RI/RI) is one of the major causes of acute kidney injury (AKI). Low molecular weight-dextran sulphate (LMW-DS) is a bioactive polysaccharide with anti-inflammatory and cytoprotective properties. This study investigated the nephroprotective potential of LMW-DS against the RI/RI. RI/RI rat model underwent surgery that involved a complete bilateral clamping of renal hila for 30 min, followed by unclamping for 30 min. LMW-DS (5 mg/kg, s.c.) was injected 5 min before unclamping. After 24 h, kidneys were collected for biochemical, histopathological, and immunohistochemical examinations. RI/RI dramatically induced renal deterioration, as reflected by marked elevation in the levels of renal oxidative stress, tumor necrosis factor-α, interleukin-6, and toll-like receptor-4, indicating lipid peroxidation and inflammatory response. Furthermore, RI/RI caused upregulation of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Additionally, morphological alterations and collagen deposition were also detected in kidney tissues. The immunohistochemical analysis revealed a strong positive immunoreaction for p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and caspase-3. Treatment with LMW-DS produced a pronounced amelioration in the altered parameters induced by RI/RI. In conclusion, LMW-DS exerts nephroprotective effects against RI/RI by restoring redox balance, suppressing inflammatory signaling, JNK/p38 MAPK, and caspase-3, highlighting its potential as a therapeutic strategy for renal I/R-induced AKI.
SN - 2076-3921
ER -