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- MakaleAçık Erişim2026Scopus SJRQ1Effects of Melatonin Formulations on Caffeine-Evoked Cortical Activity and Pentobarbital-Induced Sleep in Mice
Sahin, Nurhan; Yabas, Mehmet; Er, Besir; Erten, Fusun; Kursun, Oznur Ece Durmaz; Cikim, Ismail Gurkan; Kaplan, Berkan; Erek, Gozde; Ozmen, Busra; Orhan, Cemal
Melatonin has chronobiotic, antioxidant, anti-inflammatory, and neuromodulatory properties, and its oral effects may vary according to formulation. This study compared conventional melatonin with a lipid-multiparticulate (LMP) formulation in two acute pharmacological mouse paradigms. Eighty-four male BALB/c mice were assigned to caffeine-evoked cortical activity or pentobarbital-induced sedative-hypnotic experiments. Mice received caffeine (7.5 mg/kg, i.p.) alone or with standard or LMP-melatonin (10 or 20 mg/kg, oral). ECoG recorded cortical electrical activity under urethane anaesthesia. In a separate cohort, latency to and duration of pentobarbital-induced loss of the righting reflex were measured. Circulating neurochemical and redox markers, as well as neurotransmitter- and inflammation-related gene and protein expression, were evaluated. Caffeine increased spike frequency and altered ECoG amplitude, together with unfavorable changes in circulating neurochemical and redox markers and in neurotransmitter receptor- and inflammation-related outcomes. Both melatonin formulations attenuated several of these changes in a dose-dependent manner, with the strongest effects generally observed in the high-dose LMP-melatonin group. Compared with conventional melatonin, LMP-melatonin produced greater modulation of ECoG activity, circulating biochemical markers, neurotransmitter-receptor expression, and IL-6 and TNF-α-related outcomes. LMP-melatonin also produced a greater reduction in the latency to and a greater prolongation of the duration of pentobarbital-induced loss of the righting reflex. LMP-melatonin produced greater formulation-dependent effects than conventional melatonin on caffeine-evoked cortical electrical activity, pentobarbital-induced sedative-hypnotic responses, and selected biochemical and molecular outcomes. However, pharmacokinetic exposure, physiological sleep stages, sleep architecture, sleep quality, and direct measures of neuronal injury were not assessed. Therefore, the findings do not directly establish enhanced bioavailability, physiological sleep promotion, or neuroprotection.
- MakaleAçık Erişim2025Scopus SJRQ3EFFECTS OF LACTOBACILLUS PLANTARUM ON THE AKT/ENOS CARDIAC PATHWAY IN RATS WITH FRUCTOSE-INDUCED METABOLIC SYNDROME
Kursun, Oznur Ece Durmaz; Yalim, Goknur; Demirel, Murside Ayse; Erten, Fusun; Sahin, Kazim; Akar, Fatma
Background. This study investigated the effects of Lactobacillus plantarum supplementation on the Akt/eNOS pathway in the cardiac tissue of rats subjected to a fructose-rich diet, which induced metabolic syndrome. Materials and methods. Twenty-two male Wistar albino rats were randomly assigned to three groups: (1) control, (2) fructose, and (3) fructose ± L. plantarum. Rats in the fructose group were administered a 20% fructose solution in their drinking water for 15 weeks. In the L. plantarum-treated group, the probiotic was administered via gastric gavage at a daily dose of 1×109 CFU/mL/100 g during the final six weeks of the study. Results. The administration of Lactobacillus plantarum resulted in a significant increase in the levels of Akt (p < 0.0001), IRS-1 (p = 0.0113), mTOR (p < 0.0001), eNOS (p < 0.0001), and SIRT1 (p = 0.0031) in the cardiac tissue of rats compared to the fructose group. Moreover, a marked reduction in iNOS, NF-κB, and TNF-α levels (p < 0.0001) was observed, highlighting the potential of L. plantarum to counteract the adverse effects of fructose consumption. Conclusion. The findings of this study suggest that L. plantarum has the potential to reduce inflammation in the heart, enhance insulin sensitivity via the Akt/eNOS pathway, and protect against cardiovascular diseases associated with metabolic syndrome.
- MakaleAçık Erişim2021Scopus SJRQ2Protective Effect of Lutein/Zeaxanthin Isomers in Traumatic Brain Injury in Mice
Gunal, Mehmet Yalcin; Sakul, Ayse Arzu; Caglayan, Ahmet Burak; Erten, Fusun; Kursun, Oznur Ece Durmaz; Kilic, Ertugrul; Sahin, Kazim
Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood–brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1β), interleukin 6 (IL-6), and NF-κB levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway.
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