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    Black Garlic Extract Modulates Endothelin Expression and Ovulatory Function in Monosodium Glutamate Treated Rats
    (Wiley, 2025) Gezer, Arzu; Aras, Sukran Yediel; Ozkaraca, Mustafa; Baygutalp, Nurcan Kilic; Gundogdu, Gulhande; Sari, Ebru Karadag; Bedir, Gursel
    Monosodium glutamate (MSG), a widely used food additive, has been associated with various health concerns, including potential reproductive toxicity. This study investigated the protective effects of black garlic (BG) ethanol extract against MSG-induced ovarian damage in rats. Thirty-two female rats in estrus were randomly divided into four groups (n = 8 per group): control (saline), BG (250 mg/kg BW), MSG (4 mg/g BW), and BG+MSG (combined treatment). Treatments were administered daily for 14 days. Ovarian tissues were collected for histopathological, immunohistochemical (IHC), and biochemical analyses. Histopathological examination revealed a significant reduction in cystic follicles in the BG+MSG group compared to the MSG group (p < 0.0001). IHC analysis showed decreased immunoreactivity of endothelin-1 and endothelin-2 in the BG+MSG group compared to the MSG group (both p < 0.01). Biochemical assays demonstrated significantly increased follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels in the BG+MSG group compared to the MSG group (all p < 0.05), while progesterone levels were significantly lower in the MSG group compared to the BG+MSG group (p < 0.05). These findings suggest that BG ethanol extract may mitigate MSG-induced ovarian dysfunction in rats by alleviating degenerative changes in follicles and modulating hormonal levels. This study provides insights into potential natural interventions for MSG-related reproductive toxicity.
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    Cilomilast, a PDE4 Inhibitor, Suppresses CD4++ and CD8++ T Cell Proliferation in the Thymus and Spleen of Rats: Mechanism of Glutathione Reduction
    (Univ Agriculture, Fac Veterinary Science, 2024) Gezer, Arzu; Baygutalp, Nurcan Kilic; Cengiz, Mustafa; Gur, Bahri; Ozkaraca, Mustafa
    Cilomilast is an oral phosphodiesterase-4 (PDE4) inhibitor recommended for treating COPD. However, its side effects and low therapeutic index remain an unresolved problem in clinical practice. This study aimed to evaluate the effects of cilomilast on the spleen and thymus tissues of rats. For experimental studies, 24 male Sprague-Dawley rats weighing 200-220g were randomly divided into three experimental groups: The procedures were repeated for 7 days for the control, sham, and cilomilast groups. Blood and tissue samples were collected from the rats under anesthesia on day 8 of the experiment for analysis. p<0.05 at a 95% confidence level was considered to indicate statistical significance. Severe tissue damage in the thymus and spleen was observed in the cilomilast group. In the thymus and spleen tissues of the control and sham groups, CD4+ + and CD8+ + cell immunopositivity were more intense, while the density of these cells was significantly reduced in the cilomilast group. In addition, glutathione (GSH) levels decreased, and nitric oxide levels increased in both tissues of the cilomilast group. However, in-silico results showed that the decrease in GSH levels is due to the enzymes gamma-glutamylcysteine synthase and glutathione synthase, which act as catalysts in the two-step GSH biosynthesis mechanism. Suppression of the immune system targets both harmful and compensatory pathways so that both beneficial mechanisms and pathological changes can be blocked. To eliminate these cilomilast-induced side effects and enable more effective clinical application, it may be recommended to develop formulations such as lipid-based inhaled forms or nano-drug delivery systems including dendrimers, reverse micelle systems, polymeric or lipid-based carriers as an alternative to conventional application.
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    The Protective Effect of Gallic Acid Against Bisphenol A-Induced Ovarian Toxicity and Endocrine Disruption in Female Rats
    (Mary Ann Liebert, Inc, 2024) Gezer, Arzu; Ustundag, Hilal; Baygutalp, Nurcan Kilic; Erbas, Elif; Ozkaraca, Mustafa
    Purpose: This study aimed to investigate the protective effects of gallic acid (GA) against ovarian damage induced by bisphenol A (BPA) exposure in female rats. We evaluated whether GA can mitigate the adverse effects of BPA on ovarian structure, inflammatory markers, oxidative stress, apoptosis, and reproductive hormone levels. Methods: Thirty-two female rats were categorized into four groups: control, GA, BPA, and GA+BPA. Histopathological evaluations of ovarian tissue were performed using hematoxylin-eosin staining. The immunohistochemical analysis was conducted for inflammatory, oxidative DNA damage, and apoptotic markers (Tumor necrosis factor alpha [TNF alpha], cyclooxygenase-2 [COX2], interleukin-1 beta [IL-1 beta], 8-hydroxydeoxyguanosine [8-OHdG], and caspase 3). Oxidative stress was assessed by measuring malondialdehyde and superoxide dismutase levels. Furthermore, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone levels were quantified using enzyme-linked immunosorbent assay. Results: Histopathological outcomes revealed that BPA significantly induced follicular degeneration, which was effectively mitigated by GA treatment (P < 0.05). Immunohistochemical analysis highlighted the exacerbation of inflammatory responses and oxidative DNA damage and apoptosis (TNF alpha, COX-2, IL-1 beta, 8-OHdG, and caspase 3) in BPA-exposed tissues, which were reduced in the presence of GA (P < 0.05). The assessment of oxidative stress demonstrated that GA could significantly decrease lipid peroxidation and partially restore antioxidant defense mechanisms disrupted by BPA (P < 0.05). Hormonal profiling indicated that BPA exposure altered the levels of FSH, LH, estrogen, and progesterone, with GA treatment showing a capacity to modulate these changes, especially in progesterone levels (P < 0.05). Conclusions: The findings suggest that GA exhibits protective properties against BPA-induced ovarian damage through its antioxidative and anti-inflammatory activities, alongside its ability to modulate hormonal imbalances. This research underscores the therapeutic potential of GA in safeguarding reproductive health against environmental toxicants.