Rabbit Anti-Human FOS Polyclonal Antibody

Although physiological levels of iron are essential for numerous biological processes, excess iron causes critical tissue injury. Under iron overload conditions, non-chelated iron generates reactive oxygen species that mediate iron-induced tissue injury with subsequent induction of apoptosis, necrosis, and inflammatory responses. Because liver is a central player in iron metabolism and storage, it is vulnerable to iron-induced tissue injury. Taxifolin is naturally occurring compound that has shown potent antioxidant and potential iron chelation competency. The aim of the current study was to investigate the potential protective effects of taxifolin against iron-induced hepatocellular injury and to elucidate the underlining mechanisms using rats as a mammalian model. The results of the current work indicated that taxifolin inhibited iron-induced apoptosis and enhanced hepatocellular survival as demonstrated by decreased activity of caspase-3 and activation of the pro-survival signaling PI3K/AKT, respectively. Western blotting analysis revealed that taxifolin enhanced liver regeneration as indicated by increased PCNA protein abundance. Taxifolin mitigated the iron-induced histopathological aberration and reduced serum activity of liver enzymes (ALT and AST), highlighting enhanced liver cell integrity. Mechanistically, taxifolin modulated the redox-sensitive MAPK signaling (p38/c-Fos) and improved redox status of the liver tissues as indicated by decreased lipid peroxidation and protein oxidation along with enhanced total antioxidant capacity. Interestingly, it decreased liver iron content and down-regulated the pro-inflammatory cytokines TNF-alpha, IL-6, and IL-1 beta. Collectively, these data highlight, for the first time, the ameliorating effects of taxifolin against iron overload-induced hepatocellular injury that is potentially mediated through anti-inflammatory, antioxidant, and potential iron chelation activities.

Intestinal epithelial barrier dysfunction with dysbiosis of gut microbiota contributes to the occurrence and acceleration of colitis. This study aimed to evaluate the effect of flaxseed oligosaccharides (FOSs) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice and to elucidate the underlying mechanisms. UC was induced in mice by administering 2% DSS in drinking water for 8 days. Then, FOS (50 mg kg(-1)d(-1), 100 mg kg(-1)d(-1)and 200 mg kg(-1)d(-1)) was administered by gavage for 14 days. The results showed that FOS treatment (200 mg kg(-1)d(-1)) significantly ameliorated colitis by decreasing disease activity index (DAI), increasing colon length and improving colonic histology. FOS treatment (200 mg kg(-1)d(-1)) down-regulated the critical markers of oxidative stresses, including malondialdehyde (MDA) and myeloperoxidase (MPO). Furthermore, FOS (200 mg kg(-1)d(-1)) significantly suppressed the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and interleukin (IL)-1 beta but increased that of anti-inflammatory cytokine interleukin (IL)-10. The 16S rDNA gene high-throughput sequencing results indicated that FOS treatment increased the gut microbial diversity and inhibited the proliferation of inflammation-related bacteria such asunidentified_Clostridiales. An increase in total short-chain fatty acids (SCFAs), propionic acid and butyric acid, was also observed by FOS supplementation. FOS (200 mg kg(-1)d(-1)) also protected the intestinal barrier by increasing the protein levels of Claudin1 and Occludin. In conclusion, FOS attenuated DSS-induced colitis by modulating the gut microbiota and repairing the intestinal barrier.