Özlem Tuğçe Çilingir Kaya

Objective: Type 2 diabetes mellitus (T2DM) induces erectile dysfunction (ED) via oxidative stress and structural remodeling ofthe corpus cavernosum (CC). This study investigated the protective effects of fucoidan and intermittent fasting (IF), alone and incombination, on cavernosal impairment in a T2DM rat model.Materials and Methods: Male Sprague-Dawley rats were assigned to Control, Diabetic (streptozotocin [STZ]/nicotinamide [NA]-induced), Diabetic+Fucoidan (DF), Diabetic+IF (DIF), and Diabetic+Fucoidan+IF (DFIF) groups. After a 4-week intervention,cavernosal function was assessed using an organ bath assay. Oxidative stress was evaluated using superoxide dismutase (SOD) activityand luminol/lucigenin chemiluminescence. Structural changes were analyzed using hematoxylin and eosin (H&E), Masson’s trichrome,and endothelial nitric oxide synthase (eNOS)/alpha-smooth muscle actin (α-SMA) immunohistochemistry.Results: Type 2 diabetes mellitus induced significant trabecular disorganization and increased collagen deposition (p

Objective: This study examined the potential protective effects of memantine, an N‐methyl‐D‐aspartate (NMDA) receptor antagonist, against acoustic trauma (AT) in guinea pigs, using electrophysiological and histopathological analyses. Methods: Thirty guinea pigs with normal hearing were divided into six groups ( n = 5 per group): Group 1 (control), Group 2 (AT, early), Group 3 (AT, late), Group 4 (AT + steroid), Group 5 (AT + saline), and Group 6 (AT + memantine). AT was induced using 6–10 kHz broadband noise at 115–120 dB for 1.5–2.0 h. Animals received intraperitoneal injections of memantine, steroid, or saline 1.5 h before AT. Measurements were obtained at baseline, 2 h, 7 days, 14 days, and 21 days post‐AT. Distortion product otoacoustic emissions (DPOAE) signal‐to‐noise ratios (SNRs) were measured from 1 to 32 kHz, and auditory brainstem response (ABR) from 8 to 32 kHz. Group 2 animals were euthanized within 2 h after AT; others after the 21‐day evaluation. Cochlear histopathology was evaluated postmortem. Results: Baseline ABR thresholds were < 30 dB SPL, and DPOAE SNRs were ≥ 6 dB. Group 6 showed improved DPOAE SNRs at 1.5 and 24 kHz compared to Groups 3 and 5. ABR thresholds in Group 6 were lower than those in Group 3 (16, 24 kHz) and Group 5 (32 kHz). Group 4 showed lower thresholds than Group 3 at 12–24 kHz. Histology revealed milder cochlear damage in Group 6 compared to Groups 2, 3, and 5. Conclusion: Memantine demonstrated protective effects against noise‐induced hearing loss. Further studies are needed to clarify its molecular mechanisms.

This study aimed to investigate the effects of thymoquinone (T) and valproic acid (VPA), alone and in combination, on cardiomyocyte damage induced by absence epilepsy (AE) in rats. Adult male Wistar rats (C, T) and Genetic Absence Epilepsy Rats from Strasbourg (GAERS; AE, AE+T, AE+V, AE+V+T) were assigned to six experimental groups. C and AE received solvent; T and AE+T received thymoquinone (10 mg/kg, o.g.); AE+V received VPA (200 mg/kg, i.p.); AE+V+T received both treatments for 8 days. Hearts were collected for histological (Masson’s trichrome) and biochemical analyses. AE caused molecular changes in cardiomyocytes without fibrosis, decreasing total antioxidant status (TAS) (-8.7 %) and increasing total oxidant status (TOS) (+50.7 %), oxidative stress index (OSI) (+155.5 %), MDA (+50.8 %), caspase-8 (+43.8 %), cleaved caspase-3 (+73.5 %), NF-κB (+239.4 %), TNF-α (+141.2 %), IL-6 (+12.9 %). Compared with the AE group, T increased TAS (+48.2 %), IL-6 (+5.8 %) and reduced OSI (-36.7 %), caspase-8 (-16.0 %), cleaved caspase-3 (-37.5 %), TNF-α (-1.8 %). VPA increased TAS (+58.5 %), while reducing TOS (-15.7 %), OSI (-48.9 %), MDA (-31.9 %), IL-6 (-14.1 %), caspase-8 (-27.3 %), cleaved caspase-3 (-51.0 %), TNF-α (-8.9 %), and NF-κB (-28.5 %). The VPA+T combination further improved these alterations, decreasing TOS (-24.8 %), OSI (-54.5 %), MDA (-35.6 %), TNF-α (-16.3 %), caspase-8 (-27.7 %), cleaved caspase-3 (-47.1 %), NF-κB (-31.8 %) and IL-6 (-26.9 %) while increasing TAS (+59.8 %). Our study demonstrates that AE increases oxidative stress, apoptosis and inflammation in cardiac tissue. While T and VPA alone showed limited protective effects, their combined administration significantly attenuated cardiac damage, supporting this approach as a promising strategy for cardiac protection.

Epilepsy is associated with impaired reproductive function and testicular pathologies. Intermittent fasting (IF) is a nonpharmacological metabolic intervention with anti-inflammatory and antioxidant effects. This study investigated the protective effects of IF on testicular damage in a genetic absence epilepsy rat model (GAERS), focusing on histomorphology, oxidative stress parameters, and hormonal profiles. Testicular tissues from Wistar control (WC), Wistar + IF (WIF), GAERS control (GC), and GAERS + IF (GIF) groups (total n = 20; 5 rats per group) were evaluated using hematoxylin and eosin and Periodic Acid–Schiff staining. Apoptosis and spermatogenic cell integrity were assessed using caspase-3, P-element-induced wimpy testis (PIWI), and Deleted in Azoospermia-Like (DAZL) immunohistochemistry. Johnsen’s score, seminiferous tubule diameter, and epithelial thickness were quantified. Oxidative stress markers, including catalase, malondialdehyde, glutathione, myeloperoxidase, and superoxide dismutase, were measured using spectrophotometric methods, and serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were determined using ELISA kits. The GC group showed significantly reduced Johnsen scores, tubular diameters, and epithelial thickness, along with disrupted basement membrane integrity and increased caspase-3 immunoreactivity. IF significantly improved histological parameters, restored basement membrane integrity, reduced apoptosis, and increased PIWI and DAZL expression in the GIF group. IF also ameliorated oxidative stress and elevated reproductive hormone levels, indicating positive modulation of the hypothalamic–pituitary–gonadal axis. In conclusion, IF reduces oxidative stress and preserves seminiferous tubules and hormonal function in genetic absence epilepsy, highlighting its potential as a supportive nonpharmacological approach to protect male reproductive health.

Prolonged interaction with challenging life situations is a well-recognised risk factor for depression, anxiety, and cognitive decline, particularly among menopausal women. This research aimed to assess the effects of metformin (MF) on anxiety-like behavioural changes, cognitive impairment, brain neuroplasticity, and apoptosis induced by chronic unpredictable mild stress (CUMS) in menopausal rats. To achieve this, we conducted the open field test (OFT) to measure anxiety- like behaviours and locomotor activity, the elevated plus- maze (EPM) to assess anxiety-like behaviour, and the novel object recognition test (NORT) to evaluate recognition memory. Additionally, we measured the levels of BDNF, SIRT 1, synaptophysin, and caspase-9 by ELISA in the hippocampus, prefrontal cortex (PFC), and amygdala. Our experimental groups were categorised into five groups, with six rats in each group, as follows: Control, ovariectomized (OVX), OVX+CUMS, OVX+MF, and OVX+CUMS+MF. Four weeks after the OVX, the CUMS protocol was implemented, and MF treatment commenced following CUMS and continued for 14 days. Chronic administration of MF improved recognition memory and anxiety levels in rats subjected to CUMS, as assessed by the NORT, OFT, and EPM. MF increased brain-derived neurotrophic factor, synaptophysin, and sirtuin1, key markers of neuroplasticity in specific brain regions. We also found that MF treatment reduced pro-apoptotic caspase-9 levels. Histopathological analysis of the hippocampal DG and prefrontal cortex indicated neurodegenerative changes such as pyknotic nuclei, cytoplasmic sparseness, widespread vacuolization, and perivascular and pericellular oedema in the OVX and OVX+CUMS groups. However, these pathological features were significantly diminished in the MF groups, resulting in better preservation of neuronal integrity, fewer pyknotic cells, and reduced vacuolization. In conclusion, metformin appears to be a beneficial therapeutic agent that enhances neural plasticity, decreases apoptosis, and improves recognition memory and anxiety- like behaviours induced by OVX+CUMS

Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its popularity, systematic in vivo and in vitro safety assessments remain limited. This study aimed to comprehensively evaluate the acute oral toxicity, cytotoxicity, and genotoxicity of O. majorana methanolic extract, providing baseline toxicological data to support its safe traditional use and potential pharmaceutical applications. The methanol extract of O. majorana leaves was tested in NIH-3T3 fibroblasts for cytotoxicity and genotoxicity. In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420, with animals monitored over 14 days for clinical signs, hematological and biochemical alterations, and histopathological changes. The extract preserved fibroblast viability above 90% across all tested concentrations (10–200 µg/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg/kg. Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses. O. majorana extract demonstrates a favorable acute safety profile with preserved hepatic and renal function, hematological modulation, and absence of in vitro cytotoxicity. Nevertheless, dose-dependent genotoxicity warrants caution for concentrated formulations. According to GHS classification, the extract aligns with Category 5 (acute oral toxicity, lowest hazard) and Category 2 (germ cell mutagenicity). These findings underscore the importance of dose management and further long-term genotoxicity studies before translational applications in nutraceutical or biomedical fields.

Background/Objectives: Thymus longicaulis subsp. chaubardii (TL) (Rchb.f.) Jalas is widely used in traditional Turkish medicine for respiratory, digestive and uro-genital disorders. The aim of this study was to determine its phytochemical profile and to evaluate its cytotoxic, genotoxic and acute oral toxicity effects. Methods: The phenolic composition of the methanolic extract was determined by HPLC-DAD. Cytotoxicity and genotoxicity were evaluated in NIH3T3 cells using MTT, comet and micronucleus assays. Acute toxicity was evaluated in rats at doses of 300 and 2000 mg/kg body weight according to the OECD Guideline 420. Results: Rosmarinic acid (87.37 ± 5.39 µg/mg) was the major phenolic compound. TL extract showed >90% cell viability at 50–200 µg/mL, indicating no cytotoxicity. Comet assay revealed a slight increase in DNA damage at 100–200 µg/mL (p < 0.001), though significantly lower than the H₂O₂ group (p < 0.001). No significant (p > 0.05) effect was observed in the micronucleus assay between the treated groups. In rats, TL extract caused no mortality or behavioral changes over 14 days. No significant differences were observed in body or organ weights. Hematologically, platelet count increased (p < 0.001) and eosinophils decreased (p < 0.01 and p < 0.001). Biochemical tests showed lower ALT and AST levels (p < 0.01 and p < 0.05, respectively) and significantly decreased triglycerides in the high-dose group (p < 0.001). Histopathological examination showed no organ damage. Conclusions: The results of this study indicate that TL methanol extract is non-toxic up to 2000 mg/kg and exhibits no significant cytotoxic or genotoxic effects. These findings support its safe use and traditional medicinal value.

Epilepsy, a brain condition causing recurrent seizures, can disrupt various body functions, including urination. This study explored how alternate-day fasting (ADF), a type of intermittent fasting, a diet involving one day of eating and fasting, subsequently affects urinary system health in epileptic rats. Using a genetic rat model of epilepsy, we examined bladder and kidney function through tissue analysis, biochemical tests, and physiological assessments, focusing on differences between males and females. The results showed that epilepsy causes significant urinary system damage linked to inflammation and oxidative stress. However, ADF reduces this damage by lowering inflammation and restoring antioxidant balance. Male rats exhibited more oxidative damage, while female rats responded better to ADF, likely due to hormonal differences. These findings suggest ADF as a potential, cost-effective dietary approach to protect against urinary complications in epilepsy and similar conditions. Understanding these effects may lead to improved treatments for both genders and a better quality of life for people with chronic diseases.