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- MakaleAçık Erişim2025Scopus SJRQ1Dietary Carvacrol Attenuates Cyclophosphamide-Induced Neurotoxicity: Implications for Food-Derived Neuroprotection and Molecular Mechanisms
Kızıl, Hamit Emre
Carvacrol (CRV) is a phenolic monoterpene abundant in culinary herbs such as oregano and thyme and is well known for its potent antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the ability of CRV to counteract neurotoxicity induced by cyclophosphamide (CP), a widely used antineoplastic agent. Male Wistar albino rats were divided into five groups and received CP and/or CRV treatments. Neurotoxicity and neuroprotection were evaluated through biochemical assays, real-time PCR, histopathological and immunohistochemical analyses, and behavioral testing (Morris Water Maze). CP administration led to significant increases in oxidative stress markers, disruption of antioxidant enzyme activities, upregulation of inflammatory mediators (NF-κB, TNF-α, iNOS), dysregulation of apoptotic regulators (increased Bax and Casp-3, decreased Bcl-2), alterations in autophagy markers (Beclin-1, LC3A, LC3B), and suppression of Notch1/Hes1 signaling. Histopathological analyses revealed neuronal degeneration, vascular hyperemia, and increased GFAP and 8-OHdG expression in brain tissue. CRV treatment, particularly at higher doses, effectively mitigated these biochemical, molecular, and histological alterations. Notably, CRV administration preserved spatial learning and memory function in CP-treated rats, as demonstrated by the Morris Water Maze test, indicating functional neuroprotection. These findings highlight the multifaceted neuroprotective mechanisms of CRV and suggest its potential as a food-derived bioactive compound for development into functional foods or dietary supplements to improve the quality of life for cancer patients undergoing chemotherapy.
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İncele - MakaleAçık Erişim2024Scopus SJRQ2Interleukin-27 as a novel player in alleviating hepatic steatosis: Mechanistic insights from an in vitro analysis
Cho, Wonjun; Oh, Heeseung; Abd El-Aty, A.M.; Özten, Ömer; Jeong, Ji Hoon; Jung, Tae Woo
Interleukin-27 (IL-27) is a recently discovered cytokine that has been implicated in inflammatory and metabolic conditions, such as atherosclerosis and insulin resistance. However, the mechanisms by which IL-27 attenuates hepatic lipid accumulation in hyperlipidemic conditions and counteracts endoplasmic reticulum (ER) stress, a known risk factor for impaired hepatic lipid metabolism, have not been elucidated. This in vitro study was designed to examine the effect of IL-27 on hepatic lipid metabolism. The study included the evaluation of lipogenesis-associated proteins and ER stress markers by Western blotting, the determination of hepatic lipid accumulation by Oil Red O staining, and the examination of autophagosome formation by MDC staining. The results showed that IL-27 treatment reduced lipogenic lipid deposition and the expression of ER stress markers in cultured hepatocytes exposed to palmitate. Moreover, treatment with IL-27 suppressed CD36 expression and enhanced fatty acid oxidation in palmitate-treated hepatocytes. The effects of IL-27 on hyperlipidemic hepatocytes were attenuated when adenosine monophosphate-activated protein kinase (AMPK) or 3-methyladenine (3 MA) were inhibited by small interfering RNA (siRNA). These results suggest that IL-27 attenuates hepatic ER stress and fatty acid uptake and stimulates fatty acid oxidation via AMPK/autophagy signaling, thereby alleviating hepatic steatosis. In conclusion, this study identified IL-27 as a promising therapeutic target for nonalcoholic fatty liver disease (NAFLD).
AtıfScopus6WoS6OpenAlex6İncele