Antioxidant, anti-inflammatory and Uroprotective effects of LAMOTRIGINE Cinnamaldehyde silver complex in cyclophosphamide-induced cystitis.

Abstract

Cyclophosphamide (CYP)-induced cystitis is a significant clinical challenge in cancer patients, characterized by inflammation, oxidative stress, and muscle dysfunction. This study aimed to investigate the protective effects of lamotrigine cinnamaldehyde silver complex (LCSC) against CYP-induced cystitis. Sprague-Dawley rats were divided into six groups: Control, CYP-induced cystitis (Disease Control), mesna (standard drug), and three LCSC treatment groups (2.5, 5, and 10 mg/kg). Nociception, open-field test, bladder weight, edema, hemorrhage, vascular permeability, histopathological analysis, and the qRT-PCR expression of inflammatory and antioxidant genes were investigated. Molecular docking was performed using AutoDock Tools 1.5.6 software. LCSC treatment significantly reduced nociceptive responses and improved locomotor activity in a dose-dependent manner compared to the diseased control group. LCSC attenuated CYP-induced increases in bladder weight, edema, and hemorrhage. The higher doses of LCSC (5 and 10 mg/kg) were more effective in reducing vascular permeability. In vitro studies revealed that LCSC relaxed the urinary bladder strips in a concentration-dependent manner. LCSC also significantly upregulated the expression of antioxidant genes (catalase and superoxide dismutase) and downregulated inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor-α, and transforming growth factor-β) in a dose-dependent manner. The histopathological evaluation confirmed the preservation of bladder architecture in LCSC-treated rats. LCSC demonstrated strong binding affinities and lower inhibition constants with key inflammatory and muscle protein receptors, including IL-1β, TNF-α, MLCP, and PKC, compared to Mesna. LCSC exhibited potent antioxidant, anti-inflammatory, and uroprotective effects in the CYP-induced rat model of cystitis as a potential therapeutic drug.