Keywords
biomarkers of inflammation
antioxidant activity
ceruloplasmin
conjugated trienes
lipid peroxidation
Abstract
In press
Background. Nonsteroidal anti-inflammatory drugs are widely used to treat pain and inflammation, while combination formulations may modify treatment effects through complementary mechanisms.
Aim. To evaluate the anti-inflammatory activity of a pharmaceutical composition containing nimesulide and caffeine based on serum ceruloplasmin levels and to assess its antioxidant activity based on serum conjugated triene levels in rats with formalin-induced paw edema.
Materials and Methods. The study included 36 male Wistar Albino Glaxo rats allocated to six groups: intact control, formalin-induced paw edema, nimesulide (15 mg/kg), caffeine (0.6 mg/kg), nimesulide with caffeine (15 mg/kg and 0.6 mg/kg), and diclofenac sodium (8 mg/kg). Paw edema was induced by 2% formalin. Serum ceruloplasmin was measured by enzyme-linked immunosorbent assay (Cusabio, China), and conjugated trienes spectrophotometrically. Statistical analysis used one-way analysis of variance with Tukey's post hoc test or the Kruskal–Wallis test with Dunn's post hoc test; p<0.05 indicated significance. The study was performed within the research project "Chemical and Pharmaceutical Substantiation for the Development of Biologically Active Compositions with Anti-Inflammatory and Analgesic Activities" (2024–2026), state registration No.0124U002495.
Research Ethics. Procedures complied with the European Convention on experimental vertebrate animals and ARRIVE 2.0; the protocol was approved by the Bioethics Committee of Kharkiv National Medical University.
Results. Formalin increased serum ceruloplasmin and conjugated triene levels. The nimesulide-caffeine combination reduced ceruloplasmin to [139.83±18.42] mg/L and conjugated trienes to [0.124±0.012] arb. units/mL. These values were lower than with nimesulide or caffeine alone. Ceruloplasmin was also lower than with diclofenac sodium, while conjugated trienes did not differ significantly from the diclofenac sodium group or intact control.
Conclusions. Under the experimental conditions, the nimesulide-caffeine combination produced the largest reductions in the inflammatory and lipid-peroxidation biomarkers studied among the treatment groups. The findings support further investigation of this combination.
Keywords: experimental medicine, biomarkers of inflammation, antioxidant activity, ceruloplasmin, conjugated trienes, lipid peroxidation.
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