Uslu, Hamit; Atila Uslu, Gözde; Çoban, Taha Abdulkadir; Özkaraca, Mustafa; Kurt, Nezahat; Mendil, Ali Sefa

Background: Chemotherapeutics target cancerous cells, but they also have unavoidable toxicities in healthy tissues. Aim: In this study, the effects of the commonly used chemotherapeutic 5-fluorouracil (5FU) on lung tissue were investigated, along with the possible protective benefits of apigenin (API), hesperidin (HES), and their combination. Methodology: The study consisted of control, 5FU, API + 5FU, HES + 5FU, and API+HES + 5FU groups. API 50 mg/kg and HES 200 mg/kg were administered for 7 days. On the 8th day, 5FU was administered a dose of 100 mg/kg. Results: Analyses showed that API and HES were effective in preventing oxidative stress induced by 5FU in lung tissue, attenuating inflammation and apoptosis by suppressing MAPK/NFκB and Caspase-3/Bax/Bcl-2 pathways, suppressing autophagy by decreasing LC3B expression, and regulating Sigmar1 expression. Conclusion: These results suggest that the two flavonoids, when administered separately or in combination, may be useful in reducing side effects that often occur during the use of chemotherapeutics.

Ergul Erkec, Ozlem; Huyut, Zubeyir; Acikgoz, Eda; Huyut, Mehmet Tahir

In this study, the anti-inflammatory, antioxidative, and protective effects of ghrelin were investigated in a fat-fed streptozotocin (STZ) rat model and compared with metformin, diabetes and the healthy control groups. Histopathological evaluations were performed on H&E-stained pancreas and brain sections. Biochemical parameters were investigated by enzyme-linked immunosorbent assay. Blood glucose levels were significantly decreased with ghrelin or metformin treatments than the diabetes group. STZ administration increased brain, renal and pancreatic IL-1β, TNF-α and MDA while decreasing GPX, CAT, SOD, and NGF levels. Ghrelin increased renal GPX, CAT, NGF pancreatic GPX, SOD, CAT, NGF and brain SOD, NGF while it decreased renal, pancreatic and brain IL-1β, TNF-α and MDA levels. Ghrelin reduced neuronal loss and degeneration in the cerebral cortex and hippocampus and greatly ameliorated diabetes-related damage in pancreas. In conclusion, the data suggested that ghrelin is an effective candidate as a protectant for reducing the adverse effects of diabetes.

Uslu, Hamit; Atila Uslu, Gözde; Çiçek, Betül; Bolat, İsmail; Yıldırım, Serkan

Background: One of the most popular chemotherapy medications is doxorubicin (DOX), however it can have non-negligible damage. When the underlying mechanisms of damage are investigated, the most prominent pathways are oxidative stress, inflammation and apoptosis. Aim: We investigated the NF-κB/MAPK inflammatory pathway and cellular apoptosis to determine the efficacy of trigonelline alkaloid (TRIG) in preventing DOX-induced lung injury. Methodology: The study consisted of C, TRIG, DOX and TRIG+DOX groups. TRIG and TRIG+DOX groups received 50 mg/kg TRIG for 7 days. On day 8, DOX and TRIG+DOX groups received a single dose of 15 mg/kg DOX. Results: Our results showed that apoptosis markers and inflammation were higher in the DOX group. In contrast, TRIG pretreatment partially suppressed apoptosis and decreased inflammation by blocking the activation of the MAPK/NF-κB pathway, lowering IL-6 levels, and protecting the lung from apoptotic cell death. Conclusion: Assessing TRIG’s effectiveness in lung tissue injury, this study may be a crucial first step.

Huyut, Zübeyir; Bakan, Nuri; Yıldırım, Serkan; Akbay, Halil İbrahim; Huyut, Mehmet Tahir; Ahlatçı, Adem; Uçar, Bünyamin

Objective: This study investigated effects of zaprinast and avanafil on angiogenesis, vascular endothelial growth factor (VEGF), bone morphogenic protein (BMP) 2, 4 and 7. Methods: Female rats were randomly divided into four groups (n = 6). Sham; abdomen was approximately 2 cm opened and closed. Ovariectomised (OVX); abdomen was opened 2 cm and the ovaries were cut. OVX + zaprinast and OVX + avanafil groups; after the same procedure with OVX, 10 mg/kg zaprinast and avanafil were orally administered for 2 month, respectively. Angiogenesis and the levels of VEGF, BMP2, 4 and 7 were determined. Results: VEGF, BMP2, 4 and 7 levels in OVX + zaprinast and especially OVX + avanafil groups were higher than the sham and OVX (p <.05). However, only VEGF and BMP2 levels in OVX + zaprinast group were significant according to sham (p <.05). Also, angiogenesis in OVX + zaprinast and OVX + avanafil groups was dominant according to sham and OVX (p <.05). Conclusions: Zaprinast and avanafil induced BMP2, 4 and 7 levels synergistically with increased VEGF and angiogenesis in renal tissue.

Altay, Ahmet; Caglar, Sema; Caglar, Bulent

We investigated the anti-cancer activity of [Ag(μ-dicl)] n 1 and [AgH(nif)2] 2 complexes against human cancer cell lines (MCF-7, HT-29, and HepG2) and mouse fibroblast (3T3-L1) cell line. Anti-proliferative activity was monitored by XTT cell viability and LDH leakage assays. Cell death mode was evaluated by multi-caspase activity, annexin V cytofluorimetric, MMP, cell cycle arrest, and ROS generation assays. Antioxidant capacity was evaluated on SOD, GPx, GR, and CAT enzymes. The XTT and LDH assay results showed that both complexes exhibited strong cytotoxicity against the tested cancer cell lines. The apoptotic mechanisms of the complexes were demonstrated by loss of MMP and increase in phosphatidylserine translocation, sub-G1 phase, and multi-caspase activity. Besides, both complexes induced the oxidative stress in MCF-7 cells by decreasing the activity of GPx, GR, and CAT enzymes. In conclusion, both Ag(I) complexes, especially 1, warrant for further in vivo evaluation as a new alternative in cancer treatment.Highlights Ag(I) complexes inhibited cell proliferation and induced LDH leakage in human cancer cell lines. Ag(I) complexes induced apoptosis through MMP disruption and ROS generation. Ag(I) complexes mimicked the multi-caspase activity. Ag(I) complexes increased the accumulation of sub-G1 phase. Ag(I) complexes inhibited the activity of antioxidant system enzymes.

Burmaoglu, Serdar; Yilmaz, Ali Osman; Polat, M. Fatih; Kaya, Rüya; Gulcin, İlhami; Algul, Oztekin

In this study, we report the synthesis of novel tris-chalcones and testing of human carbonic anhydrase I, and II isoenzymes (hCA I, and hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly) inhibitors for the development of novel chalcone structures towards for treatment of some diseases. The compounds demonstrated K i values between 13.6 ± 1.1 and 50.0 ± 17.1 nM on hCA I, 9.9 ± 0.8 and 39.5 ± 15.1 nM on hCA II, 3.1 ± 0.2 and 20.1 ± 1.9 nM on AChE, 4.9 ± 0.4 and 14.7 ± 5.2 nM on BChE and 3.9 ± 0.2 and 22.4 ± 10.7 nM on α-Gly enzymes. The results revealed that novel tris-chalcones can have promising drug potential for glaucoma, leukaemia, epilepsy; Alzheimer’s disease that was associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes.

Dilek, Esra; Erol, Hüseyin Serkan; Cakir, Ahmet; Koc, Murat; Halici, Mesut Bünyami

The aim of this study is to purify carbonic anhydrase I and II isoenzymes from human erythrocyte, isolate two natural products osajin (OSJ) and pomiferin (PMF) from Maclura pomifera fruits, and evaluate the in vitro effect of these natural metabolites on these isoenzymes. These natural products may be used as starting points for drug discovery (like drugs used in several therapeutic applications, including antiglaucoma activity). For the purification procedure, the Sepharose-4B-l-tyrosine-sulphonamide affinity chromatography was used. Column chromatography and thin layer chromatography methods were used for isolation of OSJ and PMF from M. pomifera fruits and their chemical structures were elucidated by IR, 1D, and 2D NMR methods. We compared inhibitory effects of these natural products with inhibitory effects of phenolic compounds and found that these products demonstrated average inhibition effects. We thought that this study will give inspiration to scientists interested in this issue.