Züleyha Doğanyiğit’s research while affiliated with Bozok University and other places

The onset of Alzheimer’s disease (AD) is attributed to widespread amyloid beta (Aβ) plaque accumulation, tau hyperphosphorylation, oxidative stress, and neuroinflammation. However, the underlying mechanism of AD remains unclear, and no curative treatment currently exists. The aim was to investigate the effect of thymoquinone by suppressing the RAGE/NOX4 pathway in AD. Mice (n = 60) were divided into five groups, and an experimental AD model induced by an Aβ1–42 peptide was established in two groups. We also administered 5 mg/kg thymoquinone (TMQ) to the mice for its properties to slow or treat neurodegeneration in AD. Behavioral tests for memory and emotional states, micro-computed tomography (Micro CT) to assess brain volume, ELISA to measure malondialdehyde (MDA) levels, hematoxylin and eosin staining (H&E) to evaluate neuronal degeneration were used. Immunohistochemical (IHC), Western blot (WB), and real-time polymerase chain reaction (PCR) methods were used to evaluate the inhibitory effect of TMQ on a receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) signaling in AD. The results showed that TMQ may have ameliorative effects on memory, spatial learning, learning ability, and anxiety in AD. We showed that TMQ has an antioxidative effect by decreasing MDA levels by the ELSIA method (p < 0.05). There was a marked increase in neuronal degeneration in AD mice compared to other groups (p < 0.05). We concluded that TMQ could ameliorate neuronal degeneration in AD by H&E staining and suppress RAGE/NOX4 signaling by IHC and WB analysis. We concluded that TMQ could be therapeutic in AD by reducing AB expression level by IHC analysis (p < 0.05). Real-time PCR analysis showed that APP (p < 0.05), RAGE, and NOX4 (p < 0.05) gene expressions could be reduced by TMQ. In conclusion, TMQ has a high therapeutic potential in AD and an effective preventive and therapeutic strategy can be developed with more comprehensive studies on TMQ.

Tartrazine finds widespread application in the realms of alimentation, pharmaceuticals, cosmetic formulations, and textile manufacturing. Tartrazine has a negative effect on human health such as hyperactivity, allergies and asthma in children. Substances such as tartrazine might effect the embryo in a kind of aspects, containing physical or mental disorders, and a decrease in the child's intellectual memory. In this study, Sprague dawley female rats, 70–100 days old, weighing 250–300 g, with confirmed pregnancy, were divided into two groups of 5: control and tartrazine group. Rats were sacrificed on the 20th day and heart, lung, kidney and liver tissues were removed from the fetuses. The effect of tartrazine on fetal bone development was assessed by double skeletal staining, histological analysis on organs, and IL-6, IL-1β, TNF-α, and TRPM2 gene levels. It has been observed that tartrazine, which is frequently used as a food dye, damages important fetal tissues such as liver, kidney, lung and heart. A statistically meaningful reduce was observed in the total length, total area, bone length and bone area values of the limb bones in the tartrazine group compared to the control group (p < 0.05). It was observed that the mRNA levels of IL-6, IL-1β, TNF-α and TRPM2 genes in the livers of the fetuses changed compared to the control group (p < 0.05). In this study on the use of tartrazine during pregnancy, it was observed that both organs and bone development were damaged. More studies are needed on the effects of tartrazine.

Fetal alcohol syndrome (FAS) can occur because of high amount of alcohol intake during pregnancy and is characterized by both physical and neurological problems. Children diagnosed with FAS have difficulties in learning, memory, and coordination. Hippocampus has a major role in memory and learning. We aimed to determine whether alcohol exposure during pregnancy had any effect on offspring by evaluating learning ability as well as oxidative stress and autophagy in the hippocampus and cortex tissues of litters. Attention was also paid to sex differences. To do so, TRPM2, Beclin1, p62, LC3B, IBA1, parvalbumin, GAD65, and mGluR5 expression levels were evaluated by immunohistochemistry. Lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels, as well as total oxidant (TOS) and total antioxidant (TAS) status were determined by ELISA. Learning experiments were evaluated by the Morris water maze (MWM) test. Our findings demonstrated that IBA1, LC3B, GAD65, and mGluR5 expression levels were higher in female rats of the chronic alcohol exposure (CAE) model. Our IHC results revealed that TRPM2 expression levels were significantly increased in both males and females in the CAE group. Likewise, TAS was lower, and TOS was higher in CAE animals. Moreover, MWM outcomes supported a learning deficiency in CAE litters compared to controls and indicated that female offspring outperformed males in learning experiments. Therefore, our results revealed the detrimental effects of alcohol exposure during pregnancy on autophagy signaling in the hippocampus and cortex tissue of litters, which could affect the learning ability of animals.

Alcohol use disorder has negative effects on the reproductive system through the development of oxidative stress and its genotoxic effects on DNA integrity. Acute and chronic alcohol use adversely affects the male reproductive system. Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) levels, which are involved in oxidative stress, may be important in the reproductive system in alcohol use disorder. PI3K and mTOR immunoreactivities were evaluated in testicular tissue in an experimental acute and chronic alcohol intake model in male rats. Rats were divided into 3 groups as control male (n=7), acute male (n=7) and chronic male model (n=7). Histopathological analysis of testicular tissues taken from the experimental groups was performed by hematoxylin-eosin (H&E) staining. Then, testicular tissues of the experimental groups were dissected and PI3K and mTOR expressions were determined by immunohistochemistry method. According to the H&E staining results, when the experimental groups were compared with the control group; It was observed that spermatozoa were less or absent in acute and chronic groups. mTOR and PI3K expressions were significantly increased in testicular tissues belonging to chronic and acute alcohol model groups. In the chronic alcohol model, both mTOR and PI3K expressions were significantly increased compared to the acute and control groups. Our research reveal that PI3K and mTOR molecules, which are involved in oxidative stress in acute and chronic alcohol intake, may be associated with damage to the reproductive system. PI3K and mTOR proteins, can be targeted at the point of treatment against alcohol-induced reproductive damage.

Tartrazine, an azo dye prevalent in pharmaceuticals and food items, was investigated for its impact on fetal development, specifically examining visceral and skeletal abnormalities in rat offspring exposed to daily oral doses throughout pregnancy. Fourteen pregnant rats were randomly assigned to control and tartrazine groups (seven animals each), with tartrazine administered via oral gavage at 7.5 mg/kg throughout gestation. Offspring were categorized by gender for histopathological and genetic analysis of visceral structures. Bone quality and fracture resistance assessments involved micro‐CT, Raman spectroscopy, and biomechanical testing. Results highlighted distinct internal organ tissue differences in the tartrazine group, notably increased hemorrhagic and inflammatory cell infiltration, degeneration, and vacuolization compared to controls. Gender‐specific alterations in mRNA levels of IL‐6, IL‐1β, TNF‐α, and TRPM2 genes (p < .001) were also noted. Moreover, tartrazine‐exposed groups exhibited reduced trabecular thickness, bone volume, and significant alterations in bone matrix composition and quality alongside significant decreases in fracture resistance (p < 0.05). This study concludes that intrauterine exposure to tartrazine can result in adverse impacts on organ and bone development in rat offspring.

Introduction: Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide, and brings a huge burden on the quality of life of patients with TBI and the country's healthcare system. Peripheral organs, especially the kidney, and liver, may be affected by the onset of molecular responses following brain tissue damage. While secondary injury responses post TBI has been well studied in the brain, the effect/consequences of these responses in the peripheral organs have not yet been fully elucidated. Thus, our study aimed to investigate the immunoreactivity of these responses, particularly via proinflammatory cytokines and autophagy markers in the kidney and liver post-acute and chronic TBI. Material and methods: Mild TBI (mTBI) and repetitive mTBI (r-mTBI) were induced in male and female 2-month-old Balb/c mice via the Marmarou weight-drop model. Liver and kidney tissues were sampled at 24 hours (acute) and 30 days (chronic) post TBI and subjected to histopathological and immunoreactivity analysis. Results: Interleukin (IL)-6 levels were significantly increased in the male liver and kidney tissues in both TBI groups compared to the control group but were seen to be decreased in the female r-mTBI chronic liver and r-mTBI acute kidney. Tumor necrosis factor a (TNF-a) levels were found to increase only in the female r-mTBI chronic kidney tissue and mTBI chronic liver tissue. IL-1b levels were increased in the male and female r-mTBI liver tissues but decreased in the female mTBI kidney tissue. Inducible nitric oxide synthase (iNOS) levels were found to be significantly increased in the female mTBI acute and r-mTBI chronic kidney tissue and mTBI liver tissue, but decreased in the r-mTBI acute kidney and r-mTBI liver tissues. Beclin-1 levels were increased in male mTBI chronic and r-mTBI acute liver tissue but decreased in the r-mTBI chronic group. LC3A/B and P62/SQSTM1 levels were significantly increased in the female mTBI chronic and male r-mTBI chronic liver tissues but decreased in the male r-mTBI and female r-mTBI acute kidney tissues. Significant histopathological changes were also observed in the liver and kidney tissue which were dependent on the TBI severity, gender, and time post TBI. Conclusions: The results showed that TBI may elicit peripheral molecular responses, particularly in terms of alteration in the levels of inflammatory cytokines and autophagy markers, which were gender- and time-dependent. This suggests that TBI may have a significant role in the cellular damage of the kidney and liver in both the acute and chronic phases post TBI, thus ensuring that the effects of TBI may not be confined to the brain.

Background: Due to its increased volume, polycystic ovarian tissue(PCOT) is also more prone to torsion than normal tissue. In treating ovarian torsion, detorsion is applied, and oxygenation of hypoxic tissues is provided with detorsion. The oxygen radicals formed as a result cause tissue damage. Bromelain is a substance obtained from pineapple that can induce apoptosis and free radical formation in macrophages. Aim: This study aimed to evaluate the damage caused to the ovarian tissue by ischemia-reperfusion(I/R) in normal and polycystic ovaries and to investigate the role of bromelain in the damage. Study Design: Animal experimentation. Methods: First, PCOT was created by administering dihydroepiandrostenodione-sulfate to 24 rats. Then, the polycystic and normal tissue groups were divided into sham, I/R, and I/R-bromelain groups. After the procedure, all rats' ovarian and tubal tissues were taken and histopathological examination and MDA, TUNEL, NF-κB values were examined. Results: In this study, it was determined that there was a significant decrease in MDA, NF-κB values, apoptotic-cell rate evaluated by TUNEL in the groups in which bromelain was given in the ovaries of normal and PCOT rats with IR damage, compared to the group that was not provided. It was also shown that I/R damage in PCOT were more significant than in normal ovarian tissue. Conclusion: The ischemia perfusion damage in polycystic ovarian tissue may be higher than that of normal ovarian tissue. However, there needs to be a literature study investigating this issue. In these respects, this study is the first in the literature. Bromelain is a preferable agent in preventing I / R damage caused by ovarian torsion of PCOT. In addition, it is thought that Bromelain may function in treating ovary torsions, and further studies can be conducted on this subject.