Emine Sarman

This study investigated the protective effects of Cucumis melo var. agrestis Naudin (CM) at various doses against doxorubicin-induced liver and kidney injury in rats. Thirty male Wistar rats were randomly divided into five groups (n = 6 per group). DOX was administered intraperitoneally at a dose of 15 mg/kg on day 5. CM was administered orally at doses of 100, 250 or 500 mg/kg daily for ten consecutive days after DOX administration. Histological and immunohistochemical analyses were performed to evaluate tissue damage and the expression levels of caspase-3, HSP70, NF-κB p65 and TNF-α. Serum cytokines (IL-6, IL-1β, TNF-α and IL-10) and oxidative stress markers (TOS and TAS) were also measured. The DOX group exhibited significant liver and kidney damage, including hepatocellular degeneration, vascular congestion, and injury to the glomeruli and tubules, as well as increased immunoreactivity for Caspase-3, HSP70, NF-κB-p65, and TNF-α. The DOX+CM250 group showed a significant improvement in histological appearance and a marked reduction in immunoreactivity. Compared to the DOX group, this group also demonstrated decreased levels of pro-inflammatory cytokines and TOS, and increased IL-10 and TAS levels. CM significantly attenuates DOX-induced hepatotoxicity and nephrotoxicity, particularly at a dose of 250 mg/kg. Its protective effects are likely mediated through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Abbreviations: ALT – Alanine aminotransferase, AST – Aspartate aminotransferase, Bax – Bcl-2–associated X protein, Bcl-2 – B-cell lymphoma 2, BUN – Blood urea nitrogen, CM – Cucumis melo var. agrestis Naudin, DOX – Doxorubicin, GGT – Gamma-glutamyl transferase, GR – Glutathione reductase, GSH – Glutathione, HSP70 – Heat shock protein 70, IHC – Immunohistochemistry, IL – Interleukin, IL-1β – Interleukin-1 beta, IL-6 – Interleukin-6, IL-10 – Interleukin-10, MDA – Malondialdehyde, NF-κB – Nuclear factor kappa B, NF-κB p65 – Nuclear factor kappa B subunit p65, PCNA – Proliferating cell nuclear antigen, ROS – Reactive oxygen species, SOD – Superoxide dismutase, TAS – Total antioxidant status, TNF-α – Tumor necrosis factor alpha, TOS – Total oxidative status

Aims: This study aimed to investigate the potential protective effects of agomelatine (AGO) against lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats, with a focus on histopathological alterations and immunohistochemical markers of apoptosis and inflammation.Methods: A total of 32 adult female Wistar rats were randomly assigned to four groups: Control, LPS, LPS+AGO and AGO. LPS (5 mg/kg) was administered intraperitoneally to induce ALI, followed by oral AGO (20 mg/kg) treatment in the LPS+AGO group. Lung tissue samples were examined histopathologically using Hematoxylin–Eosin staining to assess edema, detachment/disruption of bronchiolar epithelium, disorganization of bronchiolar smooth muscle and thickening of the alveolar epithelium. Apoptotic and inflammatory responses were evaluated immunohistochemically via Caspase 3 (Cas-3) and tumor necrosis factor alpha (TNF-α) expression.Results: LPS administration induced significant histopathological alterations, including interstitial edema, epithelial detachment, smooth muscle disorganization and alveolar wall thickening (p

Sepsis is frequently accompanied by central nervous system involvement, leading to sepsis-associated encephalopathy characterized by neuroinflammation, microvascular dysfunction, and neuronal injury. Despite increasing recognition of its clinical impact, effective neuroprotective strategies remain limited. Modafinil (MOD), a wakefulness-promoting agent, has recently attracted attention for its anti-inflammatory, antioxidant, and neuroprotective properties in experimental models. Experimental sepsis was induced by intraperitoneal administration of lipopolysaccharide (LPS) in adult female Wistar rats. Animals were randomly assigned to four groups: control, LPS, LPS plus MOD, and MOD alone. Cerebral tissue was harvested six hours after LPS administration. Caspase-3 and tumor necrosis factor-alpha (TNF-α) expressions were assessed by immunohistochemistry. Oxidative stress was evaluated by measuring total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) in cerebral tissue homogenates. Gene expression levels of AKT1, glycogen synthase kinase 3 beta (GSK3B), sirtuin 1 (SIRT1), and heme oxygenase-1 (HO-1) were analyzed by quantitative PCR. LPS administration produced significant increases in Caspase-3 and TNF-α immunoreactivity in both cerebral cortex and cerebellum. At the oxidative stress level, LPS significantly elevated TOS and OSI while reducing TAS, indicating a pronounced shift toward pro-oxidant conditions. At the molecular level, LPS significantly increased GSK3B expression while reducing HO-1 expression. MOD treatment significantly reduced Caspase-3 and TNF-α immunoreactivity in both regions, restored the oxidative balance as evidenced by significantly attenuated TOS and OSI levels, and significantly suppressed GSK3B upregulation, whereas its effect on HO-1, AKT1, and SIRT1 expression did not reach statistical significance. MOD mitigates sepsis-induced cerebral and cerebellar injury by attenuating neuroinflammation, oxidative stress, and apoptosis. The accompanying decrease in GSK3B expression suggests that GSK3β-related signaling may contribute to these effects, although this relationship is associative rather than causal. MOD may therefore warrant further evaluation as a neuroprotective agent in sepsis-related CNS injury. Graphical Abstract

ObjectiveAllergic conjunctivitis is one of the most prevalent conditions affecting the eyes, and various medications are used in its treatment. In this study, olopatadine and verbascoside were used in combination.MethodsA factorial design was employed to evaluate the effects of Poloxamer 407 and sodium alginate. The impact of polymer concentration on parameters such as viscosity, gelation time, mucoadhesion, pH, and gelation temperature-considered indicators of ideal formulations-was assessed.ResultsThe optimal formulation, determined through the factorial design, included 0.5% sodium alginate and 20% poloxamer 407. The obtained values were: viscosity at 25 °C = 7451.8 cP, viscosity at 35 °C = 11367.3 cP, pH = 7.12, gelation temperature = 30 °C, gelation time = 52 seconds, and mucoadhesion = 0.301 N. Cytotoxicity tests on ARPE-19 and L929 cells, along with irritation studies, indicated acceptable safety profiles. In vitro release tests demonstrated an initial burst release of verbascoside and olopatadine during the first two hours, followed by a controlled release over the subsequent eight hours. Mathematical analysis of the release kinetics revealed a good fit with the Weibull model. No adverse effects were observed in rats during Draize's in vivo test.ConclusionsConsequently, the drug-loaded in situ gel formulation may be a promising option for treating allergic conjunctivitis.

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Acute lung injury secondary to sepsis remains a major problem in critical patients. Lipopolysaccharide (LPS)-induced lung injury is characterized by inflammatory infiltration, oxidative stress, and extensive apoptosis, particularly via the mitochondrial pathway. Omega-3 (OM3) polyunsaturated fatty acids have been proposed as promising modulators of inflammation and oxidative damage. However, their role in regulating mitochondria-mediated apoptosis in sepsis remains underexplored. Thirty-two female Wistar albino rats were randomized into four groups: Control, LPS (5 mg/kg, i.p. 3th), LPS-OM3 (400 mg/kg/day, i.p., 3 day), and OM3 only. After 72 h, lung tissues were collected for histopathological scoring, immunohistochemistry as tumor necrosis factor-alpha (TNF-α), heat shock protein (HSP70), caspase-3 (Cas-3); biochemical analyses as total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and qRT-PCR for mitochondrial apoptosis markers B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cytochrome-c (Cyt-c) and Cas-9. LPS induced ALI characterized by bronchiolar epithelial degeneration, alveolar hemorrhage, inflammation, and hyaline membrane formation. Biochemically, TOS and OSI levels were significantly elevated, while TAS remained unchanged. Immunohistochemical and genetic analysis showed marked upregulation of TNF-α, HSP70, and Cas-3 Bax, Cyt-c, and Casp-9 expression and decreased Bcl-2 expression in the LPS group. OM3 supplementation significantly attenuated histopathological damage, reduced oxidative stress markers, suppressed immunopositivity of proinflammatory and apoptotic proteins, and favorably modulated the apoptosis-related gene expressions. OM3 fatty acids exert a potent protective effect against LPS-induced ALI by suppressing mitochondrial apoptosis, reducing oxidative stress, and modulating the inflammatory response. These findings highlight the therapeutic potential of OM3 in mitigating sepsis-associated pulmonary damage through mitochondrial preservation.

Methotrexate (MTX), an effective immunosuppressive and antiproliferative agent, is clinically restricted by its hepatotoxic potential through oxidative stress, inflammation, and apoptosis. Dapagliflozin (DAPA), a sodium–glucose cotransporter 2 inhibitor, exhibits antioxidant and anti-inflammatory actions. This study investigated the hepatoprotective effects of DAPA against MTX-induced acute liver injury. Thirty-two female Wistar albino rats were divided into four groups (n = 8): Control, MTX (20 mg/kg), MTX + DAPA (MTX + DAPA 10 mg/kg/day for 10 days), and DAPA. Liver samples were examined histologically, immunohistochemically (Nuclear factor NF-kappa-B p65 subunit (NF-κB p65), Tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1β), Caspase (Cas)-3, Vascular endothelial growth factor (VEGF)), molecularly (Reverse transcription–polymerase chain for Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), Cytochrome C (Cyt-C), Apoptotic peptidase activating factor 1 (Apaf-1), Cas-9, Cas-3, Cas-12), and biochemically (total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI)). MTX induced severe hepatic injury with congestion, sinusoidal dilatation, and inflammatory infiltration, accompanied by upregulation of NF-κB, TNF-α, IL-1β, Bax, Cyt-C, Apaf-1, Cas-9, Cas-3, and Cas-12 and reduced Bcl-2. DAPA co-treatment significantly restored hepatic structure, suppressed inflammatory and apoptotic markers, and normalized VEGF expression, indicating reduced pathological angiogenesis. Although DAPA did not fully reverse MTX-induced weight loss, it effectively mitigated hepatocellular damage. DAPA protects against MTX-induced liver injury by inhibiting NF-κB/TNF-α/IL-1β-mediated inflammation, modulating Bax/Bcl-2–Cyt-C–Cas-dependent apoptosis, and balancing VEGF-driven angiogenesis. DAPA may thus serve as a promising hepatoprotective adjunct in MTX therapy.

Sepsis-induced acute lung injury (ALI) is a leading cause of mortality in intensive care, driven by inflammatory, apoptotic, and oxidative stress pathways. β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, exhibits anti-inflammatory and antioxidant effects, but its role in septic lung injury remains unclear. Thirty-two male Wistar rats were randomized into four groups ( n = 8 each): Control, HMB (300 mg/kg), cecal ligation and puncture (CLP), and CLP + HMB. Lung tissues were analyzed histopathologically, nuclear factor kappa B p65 (NF-κB p65) and caspase 3 (Cas-3) expression was evaluated immunohistochemically, and mRNA expression of C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), caspase 12 (Cas-12), B-cell lymphoma 2 (BCL-2), BCL-2-associated X protein (BAX), cytochrome C (Cyt-C), nuclear factor erythroid 2–related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) was measured at the molecular level. CLP induced upregulation of NF-κB p65, ER stress markers (CHOP, GRP78, Cas-12), and mitochondrial apoptotic proteins (BAX, Cyt-C, Cas-3), while downregulating BCL-2, NRF2, and GPX4 expression. HMB treatment reversed these expression changes and improved lung histopathology. HMB protects lungs in experimental sepsis by inhibiting NF-κB inflammation, reducing ER and mitochondrial apoptosis, and boosting antioxidant defenses via NRF2/GPX4. These findings support its potential as adjunct therapy for sepsis-induced ALI.