Uslu, Gozde Atila; Uslu, Hamit; Çoban, Taha Abdulkadir; Özkan, Ebru Bardas

Nobiletin (NOB) is an important flavonoid obtained from citrus fruits such as Citrus depressa, Citrus reticulata, Citrus sinensis and Citrus limon. Studies have demonstrated that effects are anti-inflammatory, antioxidant, immunomodulatory, anticancer, neuroprotective, anti-atherosclerosis, antiapoptotic, and antidiabetic. There are still limited studies on the efficacy of nobiletin on the pathways underlying gastric damage. Therefore, in the present study, we investigated both the effects of nobiletin on the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-kappa B) signaling pathway, one of the pathways in indomethacin (IND)-induced inflammation and whether it has gastroprotective activity. NOB+IND and PAN+IND groups were treated with substances for 7 days (10 mg/kg NOB, 5 mg/kg PAN). On the 8th day, gastric damage model was created with a single dose of 100 mg/kg indomethacin. In indomethacin-induced gastric injury, nobiletin significantly decreased NF-kappa B-p65, MAPK levels and significantly increased prostaglandin E2 (PGE2) production in the stomach. In addition, nobiletin administration caused a decrease in interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha) levels and an increase in interleukin 10 (IL-10) levels against indomethacin-induced inflammation. When the ulcerative areas were evaluated, it was found that ulcerative areas were significantly reduced in the nobiletin group compared to the indomethacin only group, and when the ulcer inhibition levels of nobiletin and pantoprazole administration were examined, both substances showed similar results. When these results were evaluated as a whole, it was determined that nobiletin had a candidate anti-inflammatory potential for the prevention of inflammation in the stomach and showed a strong gastroprotective effect.

Çolak, Deniz Altun; Uysal, Handan

Dioxins, furans and other polychlorinated biphenyls (coplanar PCBs) are three structural and toxicologically related families of compounds classified as the most toxic synthetic chemical. In this study, we investigated possible genotoxic effects of polychlorinated dibenzo-p-dioxins (PCDDs), man-made environmental contaminant, in Drosophila melanogaster by somatic mutation and recombination test (SMART). In this, we observe the chemical effects on wing phenotype of the transheterozygote flies carrying marker gene. Lethal doses of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,7,8,9-HXCDD, and 1,2,3,4,6,7,8,9-OCDD were determined. Doses of 1x10(-7), 2.5x10(-7), 5x10(-7), and 10x10-7 mu g/mL of PCDDs were used. In addition, the observed mutations were classified according to the size and the type of the mutations per wing. Results revealed no significant genotoxic effect of any of the dioxins tested. According to the mechanisms involved in the antigenotoxicity of PCDDs, it is suggested that the observed effects can be linked to the differences in the aryl hydrocarbon receptor (AHR) amino acid sequences in the gene protein of D. melanogaster.