Evaluation of Lacticaseibacillus casei 39 Paraprobiotic in Modulating Inflammatory and Oxidative Pathways in Acetic Acid Induced Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by mucosal inflammation, oxidative stress, and increased apoptosis. This study investigated the therapeutic effects of UV-C-inactivated Lacticaseibacillus casei 39 (paraprobiotic) in an acetic acid-induced UC rat model. The study evaluated its effects on clinical symptoms, inflammatory cytokines, oxidative stress, growth factor expression, PI3K/AKT pathway activation, and apoptotic markers. Paraprobiotic was obtained by UV-C inactivation of 108 CFU/mL L. casei 39. Female Wistar rats were divided into four groups: Control, UC, UC + Probiotic, and UC + Paraprobiotic (n = 10/group for clinical, ELISA, and oxidative stress analyses; n = 3 pooled/group for Western blot). UC was induced by rectal acetic acid administration, followed by daily oral treatments for 6 days. Clinical signs (DAI, weight change), plasma/tissue cytokines (ELISA, Western blot), oxidative stress (colon TOC/TAC), VEGF/EGF mRNA (qRT-PCR), and apoptosis/PI3K/AKT pathway proteins (Western blot) were assessed. The UC group showed severe colitis, increased TNF-α and IL-6, decreased IL-10, elevated TOC, reduced TAC, altered VEGF/EGF mRNA, PI3K/AKT activation, and increased apoptosis (Bax/Bcl-2 ratio, Cytochrome c, Caspase-9, Caspase-3). Paraprobiotic treatment improved clinical symptoms, reduced pro-inflammatory cytokines, and increased anti-inflammatory cytokines, modulated growth factor expression, reduced oxidative stress, suppressed PI3K/AKT signaling, and downregulated apoptotic markers. TOC decreased 2.10-fold (p < 0.01), TAC increased 5.43-fold (p < 0.001), and Bax/Bcl-2 ratio and Caspase-3 expression were significantly reduced (p < 0.001 vs. UC; Caspase-3 also p < 0.05 vs. UC + Probiotic). L. casei 39 paraprobiotic exhibits potent anti-inflammatory, antioxidant, and anti-apoptotic effects in UC, suggesting its promise as a novel, multi-target therapeutic agent.