Sürdürülebilir Kalkınma Amaçları
Yazarlar
- Kızıl, Hamit Emre(4)
- Kandemir, Fatih Mehmet(3)
- Akaras, Nurhan(2)
- Ayna, Adnan(2)
- Darendelioğlu, Ekrem(2)
- Dirican, Ebubekir(2)
- Gür, Cihan(2)
- Kandemir, Özge(2)
- Küçükler, Sefa(2)
- Mutlu, Hüseyin(2)
- Süzen Celbek, Büşra(2)
- Şimşek, Hasan(2)
- Aygörmez, Serpil(1)
- Caglayan, Cuneyt(1)
- Emre Kızıl, Hamit(1)
- Kaya, Yasemin(1)
- Sağ, Sevda(1)
- Takım, Uğur(1)
- Uzunçakmak, Sevgi Karabulut(1)
- Özcan, Halil(1)
Yayınlar
- MakaleAçık Erişim2026Scopus SJRQ1A 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.
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İncele - MakaleYalnız künye2026Scopus SJRQ2Multi-Pathway Renoprotection by Betanin Against Docetaxel Nephrotoxicity: Modulation of Inflammation, ER Stress, Apoptosis, and Ferroptosis
Süzen Celbek, Büşra; Akaras, Nurhan; Şimşek, Hasan; Mutlu, Hüseyin; Kızıl, Hamit Emre; Kandemir, Özge; Aygörmez, Serpil; Kandemir, Fatih Mehmet
Docetaxel (DTX), a cornerstone chemotherapeutic agent, has its clinical utility significantly limited by dose-dependent nephrotoxicity. This study investigated the multi-pathway renoprotective mechanisms of betanin (BTN), a natural antioxidant derived from beetroot, against DTX-induced kidney injury. Male Wistar rats received DTX (30 mg/kg, i.p., single dose) with or without BTN (100 mg/kg/day, p.o.) for 7 days. DTX induced severe renal dysfunction with elevated serum urea and creatinine, and significant oxidative stress characterized by increased MDA and decreased GSH, GPx, SOD, and CAT. Molecular analysis demonstrated widespread upregulation of pro-inflammatory (NF-κB, TNF-α, IL-1β), endoplasmic reticulum stress (PERK, ATF6), pro-apoptotic (Caspase-3, Bax, Apaf-1), and pro-ferroptotic (PTGS2, TfR1) mediators, with concurrent downregulation of protective Bcl-2 and GPx4. Histopathological examination revealed extensive tubular injury, while immunohistochemical analysis showed markedly increased kidney injury marker KIM-1 and decreased aquaporin-1 expression. Remarkably, BTN co-administration significantly attenuated all biochemical, molecular, and structural derangements, restored tissue architecture, and normalized KIM-1 and AQP-1 expression. In conclusion, betanin provides robust, multi-pathway renoprotection against docetaxel-induced nephrotoxicity by concurrently targeting oxidative stress, inflammation, ER stress, apoptosis, and ferroptosis.
- 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.
AtıfScopus10WoS9OpenAlex11İncele - MakaleAçık Erişim2023Investigation of the relationship between NFKB1 polymorphisms and telomere length and apoptosis in patients with type-2 diabetes
Dirican, Ebubekir; Kaya, Yasemin
Purpose: Type 2 diabetes mellitus (T2DM) is a heterogeneous, chronic, and metabolic disease that affects a significant proportion of the global population. This study aimed to evaluate the effect of NFKB1-94 ATTG ins/del polymorphisms on the expression of apoptosis genes and telomere length (TL) in patients with T2DM compared with healthy individuals.Materials and Methods: Sixty-nine T2DM patients and sixty healthy people were enrolled in the study. DNA and RNA were isolated from the blood samples. NFKB1 genotypes were identified by Sanger sequencing. For TL analyses and to investigate the expression of the caspase-3, caspase-9, bax, and bcl2 genes, RT-PCR was utilized.Results: There was a significant difference between the NFKB1-94 ins/del genotype patients and the control group (OR:0.4792 (0.2345-1.011)). However, the distribution of other genotype/alleles (ins/ins and del/del) showed no difference between T2DM and control groups. The allelic frequency of NFKB1-94 ins/del was 0.455/0.235 for the T2DM group and 0.435/0.165 for the control group. An increase in the mRNA expression of caspase-3, caspase-9 and Bax genes was observed in the T2DM group compared with the healthy group, while a decrease in the Bcl2 gene was found in the T2DM group. TL in T2DM patients was shorter than in healthy individuals.Conclusion: NFKB1-94 ins/del polymorphisms show significant differences in T2DM patients. We observed that apoptosis was activated and TL was shortened in patients with T2DM. However, no relationship between NFKB1 polymorphisms and apoptosis and TL could not be determined.
- MakaleAçık Erişim2023Scopus SJRQ2Morin ameliorates methotrexate-induced hepatotoxicity via targeting Nrf2/HO-1 and Bax/Bcl2/Caspase-3 signaling pathways
Kızıl, Hamit Emre; Caglayan, Cuneyt; Darendelioğlu, Ekrem; Ayna, Adnan; Gür, Cihan; Kandemir, Fatih Mehmet; Küçükler, Sefa
Background: Organ toxicity limits the therapeutic efficacy of methotrexate (MTX), an anti-metabolite therapeutic that is frequently used as an anti-cancer and immunosuppressive medicine. Hepatocellular toxicity is among the most severe side effects of long-term MTX use. The present study unveils new confirmations as regards the remedial effects of morin on MTX-induced hepatocellular injury through regulation of oxidative stress, apoptosis and MAPK signaling. Methods and results: Rats were subjected to oral treatment of morin (50 and 100 mg/kg body weight) for 10 days. Hepatotoxicity was induced by single intraperitoneal injection of MTX (20 mg/kg body weight) on the 5th day. MTX related hepatic injury was associated with increased MDA while decreased GSH levels, the activities of endogen antioxidants (glutathione peroxidase, superoxide dismutase and catalase) and mRNA levels of HO-1 and Nrf2 in the hepatic tissue. MTX treatment also resulted in apoptosis in the liver tissue via increasing mRNA transcript levels of Bax, caspase-3, Apaf-1 and downregulation of Bcl-2. Conversely, treatment with morin at different doses (50 and 100 mg/kg) considerably mitigated MTX-induced oxidative stress and apoptosis in the liver tissue. Morin also mitigated MTX-induced increases of ALT, ALP and AST levels, downregulated mRNA expressions of matrix metalloproteinases (MMP-2 and MMP-9), MAPK14 and MAPK15, JNK, Akt2 and FOXO1 genes. Conclusion: According to the findings of this study, morin may be a potential way to shield the liver tissue from the oxidative damage and apoptosis.
AtıfScopus74WoS71OpenAlex82İncele - MakaleAçık Erişim2023Scopus SJRQ2Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients
Dirican, Ebubekir; Özcan, Halil; Uzunçakmak, Sevgi Karabulut; Takım, Uğur
Objective: Apoptosis is programmed cell death that occurs by several pathways. Caspase-3 is induced by active caspase-9 via the intrinsic pathway. The aim of this research was to explore the expression of caspase-3 and caspase-9 in schizophrenia patients and healthy samples. Methods: RNA was isolated from the peripheral blood of 39 schizophrenia patients’ and healthy samples. After cDNA synthesis, real time PCR (RT-PCR) was used to analyse caspase-3 and caspase-9 gene expression. The severity of psychopathological symptoms of schizophrenia was evaluated using the Positive and Negative Symptoms Scale for schizophrenia (PANSS) and Clinical Global Impressions (CGI). Results: The expression of caspase-3 and caspase-9 genes was higher in schizophrenia patients than in healthy samples (p = 0.012, p = 0.002, respectively). The increase in caspase-3 gene expression was significant with being male, smoking and with a duration of less than 6 years (p = 0.047, p = 0.049, p = 0.034, respectively). On the other hand, the increase in caspase-9 gene expression was significant in patients who is smoke, have children, and are under 33 years old (p = 0.040, p = 0.043, p = 0.045, respectively). A significant positive correlation was detected between the caspase-3 and caspase-9 gene expression (r = 0.3218, p = 0.049). Conclusion: Our findings indicate that caspase-3 and caspase-9 gene expression may activate cell death mechanisms by intrinsic apoptotic genes. Furthermore, caspase-3 and caspase-9 may play essential roles in different ways in schizophrenia. Hence there is a need to further study the apoptotic mechanism with expanded patient populations.
AtıfScopus45WoS47OpenAlex42İncele - MakaleAçık Erişim2023Scopus SJRQ2Contribution of Oxidative Stress, Apoptosis, Endoplasmic Reticulum Stress and Autophagy Pathways to the Ameliorative Effects of Hesperidin in NaF-Induced Testicular Toxicity
Emre Kızıl, Hamit; Gür, Cihan; Ayna, Adnan; Darendelioğlu, Ekrem; Küçükler, Sefa; Sağ, Sevda
The ameliorative effects of hesperidin (HES) on the toxicities created by sodium fluoride (NaF) in the testes tissue of rats were studied via oxidative stress, apoptosis and endoplasmic reticulum (ER) stress pathways. The animals were divided into five distinct groups (7 rats in each group). Group 1 was control group, group 2 received NaF-only (600 ppm), group 3 received HES-only (200 mg/kg bw); group 4 received NaF (600 ppm)+HES (100 mg/kg bw) and group 5 received NaF (600 ppm)+HES (200 mg/kg bw) for 14 days. NaF-induced testes tissue damage by reducing activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and levels of glutathione (GSH), and increasing lipid peroxidation levels. NaF treatment significantly downregulated the mRNA levels of SOD1, CAT and GPx. NaF supplementation caused apoptosis in the testes by upregulating p53, NFkB, caspase-3, caspase-6, caspase-9, and Bax and downregulating Bcl-2. Furthermore, NaF caused ER stress via increasing mRNA transcript levels of PERK, IRE1, ATF-6 and GRP78. NaF treatment led to autophagy via upregulation of Beclin1, LC3A, LC3B and AKT2. In testes tissue, however, co-treatment with HES at doses of 100 and 200 mg/kg significantly reduced oxidative stress, apoptosis, autophagy and ER stress. Overall, the findings of this study suggest that HES may help to reduce testes damage caused by NaF toxicity.
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