Speaker
Abstract
Background: Cyclophosphamide (CYC) is a widely used antineoplastic agent whose clinical application is limited by several toxicities, including intestinal mucosal injury. Oxidative stress and inflammation play central roles in the development of chemotherapy-induced duodenal mucositis. Carnosic acid (CA) is a natural phenolic diterpene with potent antioxidant and anti-inflammatory properties, whereas alpha-lipoic acid (ALA) is a well-established antioxidant with additional anti-inflammatory activity.
Objective: This study aimed to investigate the protective effects of two doses of CA against CYC-induced duodenal mucositis in rats and to compare their effects with those of ALA.
Methods: Forty-two healthy male albino rats were randomly allocated into six groups (n=7/group): negative control, CYC, CA 20 mg/kg alone, CA 10 mg/kg + CYC, CA 20 mg/kg + CYC, and ALA 100 mg/kg + CYC. CA and ALA were administered orally once daily for 14 consecutive days, while CYC (150 mg/kg) was administered as a single intraperitoneal injection on day 14. Serum interleukin-17 (IL-17), interleukin-10 (IL-10), and L-citrulline levels were measured. Duodenal malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined. Nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) protein expression were assessed by Western blot analysis, while cyclooxygenase-2 (COX-2) mRNA expression was evaluated by quantitative real-time PCR. Histopathological changes in the duodenum were also examined.
Results: CYC administration markedly increased IL-17, MDA, NF-κB and TNF-α protein expression, and COX-2 mRNA expression, while decreasing IL-10, GSH, and L-citrulline levels. These biochemical and molecular alterations were accompanied by pronounced histopathological injury of the duodenal mucosa. Pretreatment with CA attenuated these alterations in a dose-dependent manner. CA at 10 mg/kg provided partial protection, whereas CA at 20 mg/kg produced greater improvement in inflammatory and oxidative stress parameters and more effectively preserved duodenal architecture. The protective effects of CA at 20 mg/kg were broadly comparable to those produced by ALA.
Conclusion: Carnosic acid attenuated CYC-induced duodenal mucositis through antioxidant and anti-inflammatory effects in a dose-dependent manner. The 20 mg/kg dose produced the most pronounced protective effect among the CA-treated groups and demonstrated an overall protective profile comparable to ALA. These findings support the potential of CA as a protective agent against chemotherapy-induced duodenal mucositis .
| Has the manuscript been published | not published |
|---|---|
| Intend to be published in the IJPS ? | NO |
