Sunset Yellow dye effects on gut microbiota, intestinal integrity, and the induction of inflammasomopathy with pyroptotic signaling in male Wistar rats.

Although concern persists regarding possible adverse effects of consumption of synthetic azo food dyes, the mechanisms of any such effects remain unclear. We have tested the hypothesis that chronic consumption of the food dye Sunset Yellow (SY) perturbs the composition of the gut microbiota and alters gut integrity. Male rats were administered SY orally for 12 weeks. Analysis of fecal samples before and after dye administration demonstrated SY-induced microbiome dysbiosis. SY treatment reduced the abundance of beneficial taxa such as Treponema 2, Anaerobiospirillum, Helicobacter, Rikenellaceae RC9 gut group, and Prevotellaceae UCG-003, while increasing the abundance of the potentially pathogenic microorganisms Prevotella 2 and Oribacterium. Dysbiosis disrupted gut integrity, altering the jejunal adherens junction complex E-cadherin/ß-catenin and decreasing Trefoil Factor (TFF)-3. SY administration elevated LPS serum levels, activated the inflammatory inflammasome cascade TLR4/NLRP3/ASC/cleaved-activated caspase-1 to mature IL-1ß and IL-18, and activated caspase-11 and gasdermin-N, indicating pyroptosis and increased intestinal permeability. The possibility that consumption of SY by humans could have effects similar to those that we have observed in rats should be examined.

Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway

Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich's solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich's ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3ß, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways