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

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.