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  • MakaleAçık Erişim2026Scopus SJRQ1
    A natural nephroprotective adjuvant for cancer chemotherapy: Rosmarinic acid disrupts IL-17 A-Ferroptosis coupling in Ifosfamide-induced renal injury

    Süzen Celbek, Büşra; Şimşek, Hasan; Akaras, Nurhan; Kandemir, Özge; Kızıl, Hamit Emre; Mutlu, Hüseyin; Kandemir, Fatih Mehmet

    Rosmarinic acid (RA) is a natural polyphenol with established pleiotropic protective effects. Ifosfamide (IFA) is a potent antineoplastic agent whose clinical utility is severely limited by dose-dependent nephrotoxicity, primarily mediated by its metabolite, chloroacetaldehyde (CAA). This study aimed to investigate whether RA protects against IFA-induced nephrotoxicity and to elucidate the underlying molecular mechanisms. Male Wistar albino rats (n = 7 per group) were allocated into four groups: Control, RA-only (50 mg/kg, p.o., 2 days), IFA-only (a single 500 mg/kg, i.p. dose), and IFA + RA. Serum biochemical markers (urea, creatinine), renal oxidative stress parameters (MDA, GSH, SOD, CAT, GPx), gene expression levels (NF-κB, TNF-α, IL-1β, IL-17 A, ACT1, TRAF6, Caspase-3, Bax, Bcl-2, PTGS2, GPX4, TfR1), and histopathological/immunohistochemical analyses (KIM-1, Nephrin, Caspase-3) were performed 24 h post-administration. IFA induced severe renal dysfunction, marked oxidative stress, and extensive histopathological damage. Mechanistically, IFA initiated a pathogenic cascade activating intrinsic apoptosis and ferroptosis, driven by a self-sustaining IL-17 A-TRAF6-NF-κB inflammatory loop. RA co-treatment (50 mg/kg) significantly reversed all functional, biochemical, and histological damage by strategically breaking this crosstalk, restoring redox homeostasis, and simultaneously restraining both cell death programs. In conclusion, RA protects against IFA nephrotoxicity by targeting the critical inflammation-ferroptosis coupling, positioning it as a highly promising adjuvant candidate for clinical use to mitigate IFA-induced renal injury.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
    AtıfScopus3WoS4OpenAlex6
    ScopusWeb of SciencePubMedİncele
  • MakaleAçık Erişim2026Scopus SJRQ1
    Effects of Moringa oleifera Oil on Adipokine Responses, Inflammation, Oxidative Stress, Bacterial Burden, and Early Survival in CLP-Induced Septic Rats

    Ülker, Ufuk; Bayraktar, Bülent; Alr, Mehmet Eray; Kızıl, Sibel; Karan, Tünay; Kotan, Gökşad Cemil; Yeni, Mustafa

    Moringa oleifera has anti-inflammatory and antioxidant properties, but its effects in polymicrobial sepsis are incompletely defined. We evaluated M. oleifera oil (MOO) in female Wistar rats subjected to cecal ligation and puncture (CLP). Forty rats were randomized to Control, Sham, CLP, CLP + MOO 100 mg/kg, or CLP + MOO 200 mg/kg (n = 8/group). At 24 h, survival, clinical scores, serum apelin, omentin-1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), recoverable bacterial burden, and histopathology were assessed. CLP decreased omentin-1 and increased IL-6, TNF-α, MDA, recoverable Staphylococcus aureus and Escherichia coli, clinical severity, and multi-organ injury. At 200 mg/kg, apelin and omentin-1 were 1.15 ± 0.12 and 28.4 ± 3.1 ng/mL, while IL-6, TNF-α, and MDA decreased to 18.4 ± 1.8 pg/mL, 24.1 ± 2.8 pg/mL, and 2.5 ± 0.3 nmol/mL, respectively. Neither organism was recovered above the detection limit. Survival was 62.5% in CLP, 87.5% with 100 mg/kg, and 100% with 200 mg/kg MOO. Within this 24 h model, a single post-CLP oral dose of MOO was associated with lower inflammatory cytokine concentrations and MDA, reduced recoverable bacterial burden, improved clinical and histopathological findings, and higher descriptive survival. Because MDA was the sole oxidative endpoint and no non-septic MOO-only group or molecular redox assays were included, these findings support the attenuation of sepsis-associated lipid peroxidation but do not establish a direct antioxidant mechanism.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
  • MakaleAçık Erişim2023Scopus SJRQ1
    The Phenolic Profile and Anti-Inflammatory Effect of Ethanolic Extract of Polish Propolis on Activated Human Gingival Fibroblasts-1 Cell Line

    Kurek-Górecka, Anna; Klósek, Malgorzata; Pietsz, Grazyna; Czuba, Zenon P.; Kolayli, Sevgi; Can, Zehra; Balwierz, Radoslaw; Olczyk, Pawel

    Propolis, owing to its antibacterial and anti-inflammatory properties, acts as a cariostatic agent, capable of preventing the accumulation of dental plaque and inhibiting inflammation. The anti-inflammatory properties of propolis are attributed to caffeic acid phenethyl ester (CAPE), which is present in European propolis. The objective of the conducted study was to assess the anti-inflammatory effects of the Polish ethanolic extract of propolis (EEP) and isolated CAPE on stimulated with LPS and IFN-alpha, as well as the combination of LPS and IFN-alpha. The cytotoxicity of the tested compounds was determined using the MTT assay. The concentrations of specific cytokines released by the HGF-1 cell line following treatment with EEP (25-50 mu g/mL) or CAPE (25-50 mu g/mL) were assessed in the culture supernatant. In the tested concentrations, both CAPE and EEP did not exert cytotoxic effects. Our results demonstrate that CAPE reduces TNF-alpha and IL-6 in contrast to EEP. Propolis seems effective in stimulating HGF-1 to release IL-6 and IL-8. A statistically significant difference was observed for IL-8 in HGF-1 stimulated by LPS+IFN-alpha and treated EEP at a concentration of 50 mu g/mL (p = 0.021201). Moreover, we observed that CAPE demonstrates a stronger interaction with IL-8 compared to EEP, especially when CAPE was administered at a concentration of 50 mu g/mL after LPS + IFN-alpha stimulation (p = 0.0005). Analysis of the phenolic profile performed by high-performance liquid chromatography allowed identification and quantification in the EEP sample of six phenolic acids, five flavonoids, and one aromatic ester-CAPE. Propolis and its compound-CAPE-exhibit immunomodulatory properties that influence the inflammatory process. Further studies may contribute to explaining the immunomodulatory action of EEP and CAPE and bring comprehensive conclusions.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
    AtıfWoS17OpenAlex19
    Web of SciencePubMedİncele
  • MakaleAçık Erişim2023Scopus SJRQ3
    Preventive and therapeutic effects of the peel powder of P. granatum in a rat sepsis model; [Preventivni i terapijski učinci praha kore pitomog šipka (P. Granatum) na modelu sepse u štakora]

    Ülker, Ufuk; Demirel, Mürşide Ayşe; Bayraktar, Bülent; Alçıgır, Mehmet Eray; Aksoy, Adil

    The aim of the present study was to evaluate the treatment potential of Punica granatum L. peel powder in an experimentally induced sepsis model in rats. Sepsis was induced in 10-week-old, male, Wistar Albino (n=24) rats. The animals were divided into four groups: Sham-operated (S) Group, Control (C) Group, Treatment-1 (T1) Group, and Treatment-2 (T2) Group. To induce the sepsis model, the cecal ligation and puncture procedure was performed. The P. granatum peel powder (200 mg/kg; per os) was applied one hour before (T1) and 10 hours after (T2) surgery in a volume of 2 mL. At the end of the experimental procedure, microbial and histopathological analyses were performed. The histopathological scores on the liver, lungs, heart, kidney, spleen, and pancreas were evaluated. Escherichia coli, Staphylococcus aureus and E. coli + S. aureus were isolated from blood cultures. Severe bacteria were detected in the blood of the group C animals. It was found that there were fewer bacteria in groups T1 (n=2) and T2 (n=4) compared with group C. There were no lesions in the pancreas tissues of any groups. Vascular changes, degeneration, and necrosis were common in the organs in all cases of group C compared to group S. The findings in group T1 were similar to those in group C, however, it was seen in fewer animals. It was determined that there was a general improvement in group T2, and in addition the existing lesions were moderate in severity. In conclusion, P. granatum L. peel powder prevented CLP-induced lung injury in experimental rats. Thus, P. granatum L. peel powder may be an alternative therapeutic agent against lung tissue injury induced by sepsis. The recovery from inflammation was better in group T2 than in the other groups. According to the results of the current study, P. granatum peel powder was found to be effective in the treatment of sepsis with antimicrobial and anti-inflammatory functions.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
    AtıfScopus1WoS1OpenAlex1
    ScopusWeb of Scienceİncele
  • MakaleAçık Erişim2022Scopus SJRQ1
    Eumelanin protects the liver against diethylnitrosamine-induced liver injury

    Altındağ, Fikret; Boğokşayan, Seda; Bayram, Sinan

    This study aims to evaluate in vivo protective effects of eumelanin (EU) on diethylnitrosamine (DEN)-induced liver injury. Wistar albino male rats were divided into 6 groups (n = 6), Control, DMSO, DEN, DEN + EU10, DEN + EU15, and DEN + EU20. Animals in the DEN group were injected i.p a single dose of 200 mg/kg DEN, DEN + EU10 group was given 10 mg/kg EU, DEN + EU15 group was given 15 mg/kg, DEN + EU20 group was given 20 mg/kg EU for a week. The results showed that there was no significant difference in vessel volume density between the groups. Inflammatory cell infiltration, hydropic degeneration, and necrotic cells were observed in the DEN group, and these histopathological changes were significantly reduced in all treatment groups. Although there was a low intensity of PAS-positive staining in the DEN groups, moderate staining was observed in the treatment groups. While Caspase-3, PCNA, TNF-α, and IL-6 expressions increased in the DEN group, their expressions decreased in the EU-treated groups. DEN increased AST, ALT, and MDA levels and decreased CAT levels. In particular, the EU10 dose significantly improved these parameters. The present study revealed that eumelanin has protective effects against DEN-induced liver injury.

    • SDG 3 · Sağlık ve Kaliteli Yaşam
    AtıfScopus9WoS8OpenAlex10
    ScopusWeb of SciencePubMedİncele