Bortezomib and quercetin as effective modulators of lipopolysaccharide-induced systemic inflammatory response and metabolic disorders
DOI:
https://doi.org/10.14739/mmt.2025.2.321622Keywords:
inflammation, systemic inflammatory response, lipopolysaccharide, bortezomib, quercetin, transcription factors, oxidative stress, nitrosative stress, carbohydrate metabolism, lipid metabolism, ratsAbstract
Aim. This study aimed to evaluate the effects of combined administration of bortezomib and quercetin on serum ceruloplasmin levels, carbohydrate and lipid metabolism parameters, and secondary products of lipid peroxidation in a lipopolysaccharide (LPS)-induced rat model.
Materials and methods. Systemic inflammatory response (SIR) was modeled in male Wistar rats by intraperitoneal administration of Salmonella typhi LPS. Rats were divided into groups: intact controls, LPS-induced SIR, and SIR groups treated with bortezomib, quercetin, or their combination. Serum ceruloplasmin, glucose, lipid profiles, nitric oxide synthase (NOS) activity, and thiobarbituric acid-reactive substances (TBARS) levels were measured. Biochemical analyses were conducted using validated spectrophotometric and enzymatic methods.
Results. Combined administration of bortezomib and quercetin showed superior efficacy in mitigating SIR markers and metabolic disruptions compared to individual treatments. Serum ceruloplasmin levels, a marker of acute-phase reaction, were normalized, indicating robust anti-inflammatory effects. Hyperglycemia associated with SIR was significantly reduced, with glucose levels returning to baseline in the combined treatment group. Lipid profile analysis revealed a marked increase in high-density lipoprotein cholesterol and reductions in very low-density lipoprotein cholesterol and triglycerides, demonstrating improved lipid metabolism. Oxidative and nitrosative stress markers, including TBARS and inducible NOS activity, were significantly lower in the combined treatment group. Enhanced constitutive NOS activity and arginase levels further supported the restoration of nitric oxide metabolism.
Conclusions. The dual administration of bortezomib and quercetin is an example of a synergistic approach to managing SIR and its metabolic consequences. This combination effectively targets both inflammatory (NF-κB inhibition) and oxidative stress (Nrf2 activation) pathways, providing better therapeutic results compared to monotherapy. These findings suggest potential clinical application of the combined use of bortezomib and quercetin in conditions characterized by chronic inflammation and metabolic disturbances.
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