Sürdürülebilir Kalkınma Amaçları
Yazarlar
- Kandemir, Fatih Mehmet(2)
- Küçükler, Sefa(2)
- Akaras, Nurhan(1)
- Altındağ, Fikret(1)
- Ayna, Adnan(1)
- Bayram, Sinan(1)
- Boğokşayan, Seda(1)
- Caglayan, Cuneyt(1)
- Darendelioğlu, Ekrem(1)
- Gür, Cihan(1)
- Kizil, Hamit Emre(1)
- Kızıl, Hamit Emre(1)
- Mutlu, Huseyin(1)
- Özdemir, Selcuk(1)
- Özer, Muhammed Rasit(1)
- Özkaraca, Mustafa(1)
Yayınlar
- MakaleYalnız künye2026Scopus SJRQ1Morin counteracts KBrO3-induced hepatotoxicity by reprogramming the HOTAIR/MEG3-miR-125b-5p/miR-214-5p axis and suppressing STAT1-associated RIPK3/MLKL necroptotic signaling
Özer, Muhammed Rasit; Özdemir, Selcuk; Küçükler, Sefa; Özkaraca, Mustafa; Kizil, Hamit Emre; Akaras, Nurhan; Mutlu, Huseyin; Kandemir, Fatih Mehmet
Potassium bromate (KBrO3; PB), an oxidative contaminant in ozonated water and bakery products, induces multi-mechanistic hepatotoxicity. Its epigenetic, necroptotic, and metabolic injury dimensions remain poorly characterized. Morin (MOR), a dietary flavonoid with established antioxidant and anti-inflammatory properties, has not previously been evaluated against PB-induced subacute hepatotoxicity. To characterize MOR's hepatoprotective mechanisms against PB-induced liver injury, focusing on the HOTAIR/MEG3-miRNA epigenetic axis, STAT1-associated RIPK3/MLKL necroptotic signaling, and Glut2/HPGD-AKT/mTOR metabolic signaling. Male Sprague-Dawley rats (n = 28) were assigned to Control, MOR (100 mg/kg), PB (62 mg/kg), and PB + MOR groups for 14 days. Outcomes included hepatobiliary biochemistry, oxidative stress markers, inflammatory mediators (ELISA), lncRNA/miRNA/mRNA profiling (RT-qPCR), immunohistochemistry (RIPK3, MLKL), double immunofluorescence (Glut2/AKT1; HPGD/mTOR), histopathology, and PCA. PB produced marked redox imbalance (up arrow MDA; down arrow SOD, CAT, GPx), NF-kappa B/NLRP3-associated inflammatory mediator elevation, epigenetic disruption (up arrow HOTAIR, down arrow MEG3; up arrow miR-125b-5p/down arrow BCL2L2; down arrow miR-214-5p/up arrow SMAD4), upregulation of STAT1-associated necroptosis-related transcripts and proteins (up arrow RIPK1/RIPK3/MLKL), and metabolic dysfunction (down arrow Glut2, down arrow HPGD; up arrow AKT1/mTOR). MOR restored redox balance, suppressed inflammation, and reprogrammed the miRNA axis while normalizing MLKL (transcript and immunohistochemistry) and AKT1 and partially attenuating RIPK3, mTOR, and STAT1. MOR confers multi-targeted hepatoprotection by restoring redox and metabolic homeostasis, attenuating NF-kappa B/NLRP3-associated inflammation, reprogramming HOTAIR/MEG3-miRNA epigenetics, and attenuating STAT1-associated RIPK3/MLKL signaling, supporting its potential as a dietary hepatoprotective candidate. PB is associated with engagement of the hepatic STAT1/RIPK3/MLKL axis and disrupts the HOTAIR/MEG3-miRNA network-both previously undocumented for this toxicant. MOR partially restores miR-214-5p/miR-466 expression while suppressing their downstream effector SMAD4, consistent with attenuation of pro-fibrotic signaling. Future work should employ multi-dose designs, in vitro mechanistic dissection, sex-stratified analyses, and clinical pharmacokinetic profiling to advance MOR toward translational application.
- 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.
AtıfScopus74WoS71OpenAlex82
İncele - MakaleAçık Erişim2022Scopus SJRQ1Eumelanin 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.
AtıfScopus9WoS8OpenAlex10İncele