Sebin, Saime Ozbek; Gulakar, Basak; Tanyeli, Ayhan; Guler, Mustafa Can; Erbas, Elif; Baser, Sumeyye; Celebi, Demet

Acute kidney damage frequently results from renal ischemia–reperfusion (RI/R). Alpha-Pinene (AP), a plant-derived monoterpene, has antioxidant, anti-inflammatory, and anti-apoptotic properties. We investigated whether AP limits early kidney damage after experimental RI/R. Female Wistar rats (n = 7 per group) were assigned to Sham, RI/R, RI/R + AP 50 mg/kg, or RI/R + AP 100 mg/kg. After 45 min of clamping both renal pedicles, a 24-h reperfusion period ensued. AP (i.p. immediately before reperfusion) was administered immediately before reperfusion. ELISA for inflammatory cytokines (IL-1β, TNF-α, IL-10), oxidative stress markers (MDA, IMA, SOD), and nitric oxide synthase isoforms (iNOS, eNOS). Histopathology (hematoxylin/Mallory's trichrome staining) for structural kidney injury scoring. Immunohistochemistry for apoptosis/autophagy markers (Bcl-2, cleaved caspase-3, LC3B) and NF-κB p65. In kidney homogenates, RI/R increased IL-1β, TNF-α, MDA, IMA, and iNOS and reduced IL-10, SOD, and eNOS compared to Sham. AP counteracted these alterations in a manner proportional to the dose; the 100 mg/kg dose most consistently approached Sham values. Histology showed diffuse vascular congestion/hemorrhage, tubular degeneration, and widening of Bowman's space after RI/R—all ameliorated by AP, with milder lesions at 100 mg/kg. Immunohistochemistry demonstrated lower cleaved caspase-3, LC3B, and NF-κB p65 (trend) with AP, alongside higher Bcl-2, supporting anti-apoptotic and anti-autophagic effects. A single intraperitoneal dose of AP administered immediately before reperfusion mitigated early renal injury after RI/R by improving redox balance, dampening inflammatory signaling, shifting the eNOS/iNOS profile toward endothelial protection, and reducing structural damage. AP merits further study as a potential adjunct to limit I/R–related kidney injury, including longer follow-up with functional renal endpoints and expanded dosing/timing strategies.

Üstündağ, Hilal; Kara, Adem; Gökhan Taş, Necip; Danişman Kalindemi̇rtaş, Ferdane; Kurt, Nezahat; Erbaş, Elif; Tahir Huyut, Mehmet; Gül, Mustafa; Afşin Kari̇per, İshak

Sepsis-associated acute lung injury continues to pose a significant medical challenge with substantial morbidity and mortality rates. In this study, we investigated the therapeutic potential of propolis-based treatments and their nanocomposites in modulating inflammation and apoptosis using a lipopolysaccharide (LPS)-induced rat model of sepsis. Forty-two Sprague-Dawley rats were divided into seven groups (n = 6): control, LPS (5 mg/kg, i.p.), LPS + Propolis (100 mg/kg, i.p.), LPS + NanoPropolis (100 mg/kg, i.p.), LPS + silver nanoparticles propolis (AgNPsPro) (50 mg/kg), and a negative propolis group (100 mg/kg, i.p.). The rats were assessed for inflammatory, oxidative stress, and apoptotic markers through Western blot, histopathological analyses, and biochemical measurements. The LPS group exhibited significantly higher levels of pro-inflammatory cytokines (IL-1β, TNF-α) and the systemic infection marker presepsin (PRSN) in blood, as well as the oxidative stress marker malondialdehyde (MDA) in lung tissue. The treatment groups, particularly LPS + AgNPsPro, showed significant reductions in these markers, with decreased levels of MDA, IL-1β, TNF-α, NF-κB, and TLR4, and increased GSH content in lung tissue (p < 0.05). The anti-apoptotic protein BCL-2 was upregulated, while pro-apoptotic BAX expression was reduced, indicating enhanced cell survival. The P2X7 receptor, a key inflammation regulator, and the AKT signaling pathway, involved in cell survival, were positively modulated by the treatments. Histopathological findings corroborated these results, showing less lung tissue damage. In conclusion, propolis-based treatments, especially in combination with nanoparticles, demonstrate therapeutic potential in reducing inflammation, oxidative stress, and apoptosis in sepsis-induced lung injury.

Üstündağ, Hilal; Kara, Adem; Taş, Necip Gökhan; Kalindemirtaş, Ferdane Danişman; Kurt, Nezahat; Erbaş, Elif; Huyut, Mehmet Tahir; Gül, Mustafa; Kari̇per, İshak Afşin

The authors regret < The authors regret that there was an error in the funding information. The incorrect funding information reads: “This study was supported by the Scientific Research Projects Coordination Unit of Erzincan Binali Yıldırım University, under Project Code TSA-2022-854.” The correct funding information should be: "This study was supported by the Scientific Research Projects Coordination Unit of Erzincan Binali Yıldırım University, under Project Code TSA-2023-929.">. The authors would like to apologise for any inconvenience caused.

Erbaş, Elif; Üstündağ, Hilal; Öztürk, Emre; Parlak, Seçil Nazife; Atcalı, Tuğçe

Objective: This study aimed to evaluate the protective effects of astaxanthin against lithium-induced nephrotoxicity, focusing on histopathological changes, oxidative stress modulation, and alteration in the expression of key proteins related to apoptosis and inflammation. Methods: In this study, 56 male rats were utilized and divided into experimental groups subjected to lithium-induced nephrotoxicity, with and without astaxanthin treatment, over 14 and 28 days. The parameters assessed included oxidative stress markers (MDA, GSH, SOD), protein expression levels of BCL-2, BAX, TNF- α, PI3K, NF-κ B-p65, IL-1β, and comprehensive histopathological examinations to evaluate the integrity of renal tissue. Results: Lithium exposure led to significant renal damage, as evidenced by histological distortions in renal architecture, increased oxidative stress indicated by elevated MDA levels, and dysregulated expressions of apoptotic and inflammatory proteins. Notably, histopathological analysis revealed glomerular and tubular degeneration in lithium-treated groups. Astaxanthin treatment effectively mitigated these effects, demonstrating its efficacy in reducing lipid peroxidation, rebalancing apoptotic proteins, suppressing pro-inflammatory cytokines, and preserving renal histological structure. The concurrent use of lithium and astaxanthin showed a considerable amelioration of lithium-induced damage, suggesting astaxanthin's role in attenuating the nephrotoxic effects of lithium, both at a molecular and structural level. Conclusion: Astaxanthin demonstrates significant renoprotective effects against lithium-induced nephrotoxicity, suggesting its utility as an effective adjunctive therapy. Through its potent antioxidative, anti-inflammatory, and anti-apoptotic actions, astaxanthin effectively reduces renal damage associated with lithium treatment, underscoring its potential for enhancing renal health in patients receiving lithium therapy.

Gezer, Arzu; Ustundag, Hilal; Mendil, Ali Sefa; Bedir, Gursel; Duysak, Lale

Objective: The hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. Methods: Thirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). Results: α-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. Conclusion: Resveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.