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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Molsidomine Pretreatment Modulates Renal Redox and Endothelial Activation Markers in Experimental Polymicrobial Sepsis

  • Adem Kose1
  • Zeynep Busra Keser1
  • Mehmet Gul2
  • Seyma Yasar3
  • Onural Ozhan4
  • Zeynep Ulutas5
  • Feyzi Dogru6
  • Ezgi Kurucay2
  • Ayse Betul Levent2
  • Mehmet Ertugrul Balkar4
  • Hakan Parlakpinar4
6 affiliations
  1. 1Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Inonu University, 44280 Malatya, Türkiye
  2. 2Department of Histology and Embryology, Faculty of Medicine, Inonu University, 44280 Malatya, Türkiye
  3. 3Department of Biostatistics and Medical Informatics, Faculty of Medicine, Inonu University, 44280 Malatya, Türkiye
  4. 4Department of Pharmacology, Faculty of Medicine, Inonu University, 44280 Malatya, Türkiye
  5. 5Department of Cardiology, Faculty of Medicine, Inonu University, 44280 Malatya, Türkiye
  6. 6Department of Physiology, Faculty of Medicine, Malatya Turgut Ozal University, 44210 Malatya, Türkiye
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Abstract

Sepsis-associated renal injury involves oxidative, inflammatory, and microvascular disturbances. This study evaluated renal changes associated with molsidomine pretreatment in cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Forty Wistar rats were randomly allocated to Sham (n = 8), molsidomine (MOL; n = 8), CLP (n = 12), or MOL+CLP (n = 12) groups. Molsidomine (10 mg/kg/day) was administered orally for 14 days before surgery. Four animals in each septic group died before 24 h, leaving eight survivors per group. The primary outcome was total renal histopathological damage score; secondary outcomes included renal biochemical and immunohistochemical markers and serum renal indices. The total histopathological score differed across groups (overall p < 0.001) and was lower in surviving MOL+CLP than CLP animals (2.22 ± 0.97 vs. 5.38 ± 1.06). All four injury components were numerically lower, but adjusted pairwise differences were significant only for glomerular capillary collapse and renal tubular injury. Compared with CLP, MOL+CLP showed lower renal malondialdehyde (106.41 ± 9.03 vs. 136.45 ± 20.27 nmol/g), higher superoxide dismutase and glutathione peroxidase activities, and lower VEGF and P-selectin immunoreactivity. Renal nitric oxide, other redox and inflammatory markers, and serum creatinine, blood urea nitrogen, and urea did not differ significantly between septic groups after multiplicity adjustment. Among survivors, molsidomine pretreatment was associated with less pronounced renal structural injury and tissue-level abnormalities, without significant differences in conventional serum renal indices. Its effects when initiated after sepsis onset remain unknown. Further studies should evaluate post-sepsis dosing, antimicrobial and supportive care, and longer-term renal functional outcomes.

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Cite

BibTeXRIS
BibTeX
@article{kose2026molsidomine,
  title = {{Molsidomine Pretreatment Modulates Renal Redox and Endothelial Activation Markers in Experimental Polymicrobial Sepsis}},
  author = {Adem Kose and Zeynep Busra Keser and Mehmet Gul and Seyma Yasar and Onural Ozhan and Zeynep Ulutas and Feyzi Dogru and Ezgi Kurucay and Ayse Betul Levent and Mehmet Ertugrul Balkar and Hakan Parlakpinar},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209088},
  url = {https://www.mdpi.com/1422-0067/27/20/9088},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Molsidomine Pretreatment Modulates Renal Redox and Endothelial Activation Markers in Experimental Polymicrobial Sepsis
AU  - Adem Kose
AU  - Zeynep Busra Keser
AU  - Mehmet Gul
AU  - Seyma Yasar
AU  - Onural Ozhan
AU  - Zeynep Ulutas
AU  - Feyzi Dogru
AU  - Ezgi Kurucay
AU  - Ayse Betul Levent
AU  - Mehmet Ertugrul Balkar
AU  - Hakan Parlakpinar
PY  - 2026
DA  - 2026/10/14
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209088
UR  - https://www.mdpi.com/1422-0067/27/20/9088
AB  - Sepsis-associated renal injury involves oxidative, inflammatory, and microvascular disturbances. This study evaluated renal changes associated with molsidomine pretreatment in cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Forty Wistar rats were randomly allocated to Sham (n = 8), molsidomine (MOL; n = 8), CLP (n = 12), or MOL+CLP (n = 12) groups. Molsidomine (10 mg/kg/day) was administered orally for 14 days before surgery. Four animals in each septic group died before 24 h, leaving eight survivors per group. The primary outcome was total renal histopathological damage score; secondary outcomes included renal biochemical and immunohistochemical markers and serum renal indices. The total histopathological score differed across groups (overall p < 0.001) and was lower in surviving MOL+CLP than CLP animals (2.22 ± 0.97 vs. 5.38 ± 1.06). All four injury components were numerically lower, but adjusted pairwise differences were significant only for glomerular capillary collapse and renal tubular injury. Compared with CLP, MOL+CLP showed lower renal malondialdehyde (106.41 ± 9.03 vs. 136.45 ± 20.27 nmol/g), higher superoxide dismutase and glutathione peroxidase activities, and lower VEGF and P-selectin immunoreactivity. Renal nitric oxide, other redox and inflammatory markers, and serum creatinine, blood urea nitrogen, and urea did not differ significantly between septic groups after multiplicity adjustment. Among survivors, molsidomine pretreatment was associated with less pronounced renal structural injury and tissue-level abnormalities, without significant differences in conventional serum renal indices. Its effects when initiated after sepsis onset remain unknown. Further studies should evaluate post-sepsis dosing, antimicrobial and supportive care, and longer-term renal functional outcomes.
SN  - 1422-0067
ER  -