Browsing by Author "Kiliclioglu, Metin"

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Impact of Long-Term Deltamethrin Exposure on Alzheimer's-Related Neurodegeneration in Rats
(Academic Press Inc Elsevier Science, 2025) Altun, Serdar; Ozdemir, Selcuk; Arslan, Harun; Kiliclioglu, Metin; Yaprak, Esra; Bolat, Smail; Aydin, Seyma
In recent years, epidemiological studies have emerged indicating a potential association between chronic exposure to pesticides and the development of chronic neurodegenerative nervous system diseases such as Alzheimer's disease. In this study, we aimed to investigate the potential role of long-term nonfatal exposure to Deltamethrin in spreading this disease. To this end, a range of aspects of brain damage were discussed in rats administered deltamethrin in oral doses of 0.65 mg/kg b.w. and 1.3 mg/kg b.w. for 30 days. The activation of beta-amyloid, the primary component of plaques characteristic of Alzheimer's disease, and the NG2, a type 1 transmembrane protein, was assessed by immunohistochemistry and western blot methods in rat brain. In addition, the expression level of the APP, GFAP, NfL, TNF-alpha, CXCL9, CCL5, and IL-1 alpha genes in deltamethrin-exposed brain tissue was measured using qRT-PCR. In addition, levels of pTau181 and Abeta42 were measured with ELISA. A strong positive immunohistochemical reaction for beta-amyloid was detected in the deltamethrin-exposed brain tissues. A decrease in NG2 immunofluorescence positivity was found in the application groups compared to the control group. It was demonstrated that deltamethrin exposure significantly up-regulated the expressions of APP, GFAP, NfL, TNF-alpha, CXCL9, CCL5, and IL-1 alpha genes, also significantly higher the levels of pTau181 and Abeta42 (pg/ml) in rat brain tissues. This study provides scientific evidence that exposure to chronic doses of deltamethrin may play a positive role in the development of diseases such as Alzheimer's. Future studies should investigate similar projects and expand knowledge on the topic.
Multi-Tissue Network Analysis Reveals the Effect of Jnk Inhibition on Dietary Sucrose-Induced Metabolic Dysfunction in Rats
(eLife Sciences Publishing Ltd, 2025) Yang, Hong; Zhang, Cheng; Kim, Woonghee; Shi, Mengnan; Kiliclioglu, Metin; Bayram, Cemil; Mardinoglu, Adil
Excessive consumption of sucrose, in the form of sugar-sweetened beverages, has been implicated in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD) and other related metabolic syndromes. The c-Jun N-terminal kinase (JNK) pathway plays a crucial role in response to dietary stressors, and it was demonstrated that the inhibition of the JNK pathway could potentially be used in the treatment of MAFLD. However, the intricate mechanisms underlying these interventions remain incompletely understood given their multifaceted effects across multiple tissues. In this study, we challenged rats with sucrose-sweetened water and investigated the potential effects of JNK inhibition by employing network analysis based on the transcriptome profiling obtained from hepatic and extrahepatic tissues, including visceral white adipose tissue, skeletal muscle, and brain. Our data demonstrate that JNK inhibition by JNK-IN-5A effectively reduces the circulating triglyceride accumulation and inflammation in rats subjected to sucrose consumption. Coexpression analysis and genome-scale metabolic modeling reveal that sucrose overconsumption primarily induces transcriptional dysfunction related to fatty acid and oxidative metabolism in the liver and adipose tissues, which are largely rectified after JNK inhibition at a clinically relevant dose. Skeletal muscle exhibited minimal transcriptional changes to sucrose overconsumption but underwent substantial metabolic adaptation following the JNK inhibition. Overall, our data provides novel insights into the molecular basis by which JNK inhibition exerts its metabolic effect in the metabolically active tissues. Furthermore, our findings underpin the critical role of extrahepatic metabolism in the development of diet-induced steatosis, offering valuable guidance for future studies focused on JNK-targeting for effective treatment of MAFLD.