Anti-inflammatory and protective effects of Aripiprazole on TNBS-Induced colitis and associated depression in rats: Role of kynurenine pathway

• Published in: International immunopharmacology Vol. 133; p. 112158
• Main Authors: Mohammadgholi-Beiki, Afrooz, Sheibani, Mohammad, Jafari-Sabet, Majid, Motevalian, Manijeh, Rahimi-Moghaddam, Parvaneh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-05-2024
• Subjects: Aripiprazole; Depression; Inflammation; Inflammatory bowel disease; Kynurenine pathway; Rat; KYNA; BBB; Rat; CNS; IBD; Aripiprazole; UC; LPS; NF-κB; IFN-γ; IDO; ANOVA; SPT; NMDA; OFT; Kynurenine pathway; CD; BCA; KP; D2R; FST; H&E; TBST; Depression; i.p; Inflammation; IL-13; IL-1β; TNBS; PVDF; IL-6; 5-HTR; QUIN; Inflammatory bowel disease; SDS-PAGE; ZO-1; PEG; TNF-α; ARP; ELISA
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.112158

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•ARP’s effect on TNBS-induced colitis and depression was studied for the first time.•ARP significantly ameliorated intestinal damage at macroscopic and microscopic levels.•ARP could reduce the expression of NF-κB and inflammatory cytokines in the colon.•ARP significantly improved depressive-like behaviors in TNBS-treated (colitis) rats.•ARP could modulate the KP in the colon and hippocampus tissues of IBD animals.
The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Inflammatory cytokines and the kynurenine pathway (KP) play important roles in IBD and associated depression. Aripiprazole (ARP), an atypical antipsychotic, shows various anti-inflammatory properties and may be useful in treating major depressive disorder. This study aimed to evaluate the protective effects of ARP on TNBS-induced colitis and subsequent depression in rats, highlighting the role of the KP.
Fifty-six male Wistar rats were used, and all groups except for the normal and sham groups received a single dose of intra-rectal TNBS. Three different doses of ARP and dexamethasone were injected intraperitoneally for two weeks in treatment groups. On the 15th day, behavioral tests were performed to evaluate depressive-like behaviors. Colon ulcer index and histological changes were assessed. The tissue levels of inflammatory cytokines, KP markers, lipopolysaccharide (LPS), nuclear factor-kappa-B (NF-κB), and zonula occludens (ZO-1) were evaluated in the colon and hippocampus.
TNBS effectively induced intestinal damages and subsequent depressive-like symptoms in rats. TNBS treatment significantly elevated the intestinal content of inflammatory cytokines and NF-κB expression, dysregulated the KP markers balance in both colon and hippocampus tissues, and increased the serum levels of LPS. However, treatment with ARP for 14 days successfully reversed these alterations, particularly at higher doses.
ARP could alleviate IBD-induced colon damage and associated depressive-like behaviors mainly via suppressing inflammatory cytokines activity, serum LPS concentration, and affecting the NF-κB/kynurenine pathway.