Molecular mechanisms of resveratrol and its silver nanoparticle conjugate in addressing sepsis-induced lung injury.

Sepsis is a life-threatening condition characterized by a systemic inflammatory response to infection. Despite extensive research on its pathophysiology, effective therapeutic approaches remain a challenge. This study investigated the potential of resveratrol (RV) and silver nanoparticle-enhanced resveratrol (AgNP-RV) as treatments for sepsis-induced lung injury using a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The study focused on evaluating changes in oxidative status (TAS, TOS, and OSI) and the expression of inflammatory and apoptotic markers (IL-1ß, TNF-α, P2X7R, TLR4, Caspase-3, and Bcl-2) in lung tissue. Both RV and AgNP-RV demonstrated potential in mitigating oxidative stress, inflammation, and apoptosis, with AgNP-RV exhibiting greater efficacy than RV alone (p < 0.05). These findings were corroborated by histopathological analyses, which revealed reduced tissue damage in the RV- and AgNP-RV-treated groups. Our study highlights the therapeutic potential of RV and, particularly, AgNP-RV in combating sepsis-induced oxidative stress, inflammation, and apoptosis. It also underscores the promise of nanoparticle technology in enhancing therapeutic outcomes. However, further investigations are warranted to fully understand the mechanisms of action, especially concerning the role of the P2X7 receptor in the observed effects. Nonetheless, our research suggests that RV and AgNP-RV hold promise as novel strategies for sepsis management.

ENHANCED EFFICACY OF RESVERATROL-LOADED SILVER NANOPARTICLE IN ATTENUATING SEPSIS-INDUCED ACUTE LIVER INJURY: MODULATION OF INFLAMMATION, OXIDATIVE STRESS, AND SIRT1 ACTIVATION.

ABSTRACT: Sepsis-induced acute liver injury is a life-threatening condition involving inflammation, oxidative stress, and endothelial dysfunction. In the present study, the preventive effects of resveratrol (RV) alone and RV-loaded silver nanoparticles (AgNPs + RV) against sepsis-induced damage were investigated and compared in a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Rats were divided into four groups: Sham, CLP, RV, and AgNPs + RV. Pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, presepsin, procalcitonin (PCT), 8-hydroxy-2'-deoxyguanosine (8-OHDG), vascular endothelial growth factor (VEGF), and sirtuin-1 (SIRT1) levels were assessed to determine the treatments' effects. AgNPs + RV treatment significantly reduced pro-inflammatory cytokines, NF-κB activation, presepsin, PCT, 8-OHDG, and VEGF levels compared with the CLP group, indicating attenuation of sepsis-induced liver injury. Both RV and AgNPs + RV treatments increased SIRT1 levels, suggesting a potential role of SIRT1 activation in mediating the protective effects. In conclusion, AgNPs + RV treatment demonstrated extremely enhanced efficacy in alleviating sepsis-induced liver injury by modulating inflammation, oxidative stress, and endothelial dysfunction, potentially mediated through SIRT1 activation. In this study, the effect of AgNPs + RV on sepsis was evaluated for the first time, and these findings highlight AgNPs + RV as a promising therapeutic strategy for managing sepsis-induced liver injury, warranting further investigation.

A new treatment approach: Melatonin and ascorbic acid synergy shields against sepsis-induced heart and kidney damage in male rats.

AIM: To investigate the combined therapeutic potential of melatonin and ascorbic acid in mitigating sepsis-induced heart and kidney injury in male rats and assess the combination therapy's effects on inflammation, cellular damage, oxidative stress, and vascular function-related markers. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) induced sepsis in male rats, which were divided into five groups: Sham, CLP, MEL (melatonin), ASA (ascorbic acid), and MEL+ASA (melatonin and ascorbic acid). Rats were treated, and heart and kidney tissues were collected for biochemical and histopathological analyses. Inflammatory markers (presepsin, procalcitonin, NF-κB, IL-1ß, IL-6, TNF-α), cellular damage marker (8-OHDG), oxidative status, nitric oxide (NO), vascular endothelial growth factor (VEGF), and sirtuin 1 (SIRT1) levels were assessed. KEY FINDINGS: Melatonin and ascorbic acid treatment reduced inflammatory and cellular damage markers compared to the CLP group. Combined treatment improved NO, VEGF levels, and increased SIRT1 expression, suggesting a synergistic effect in mitigating sepsis-induced inflammation, cellular damage, and oxidative stress. Histopathological analyses supported these findings, revealing reduced heart and kidney injury in the MEL+ASA group. SIGNIFICANCE: Our study highlights potential benefits of combining melatonin and ascorbic acid as a therapeutic strategy for alleviating sepsis-induced heart and kidney injury. The synergistic effects of these agents may provide stronger protection against inflammation, oxidative stress, and tissue damage, opening new avenues for future research and clinical applications in sepsis management.

Protective role of melatonin against testicular damage caused by polymicrobial sepsis in adult rats.

BACKGROUND: This study aimed to investigate the possible protective effects of melatonin (MEL) against the damage to testicular tissue in rats caused by polymicrobial sepsis as a result of cecal ligation and perforation (CLP). METHODS: In this study, 21 male Wistar albino rats were used. The rats were randomly divided into three groups (n=7): Sham Control (Group 1), CLP (Group 2), and CLP + MEL (Group 3). Sepsis was created using the CLP method. MEL was administered intraperitoneally in two equal doses of 10 mg/kg at 30 min before and 6 h after perforation. Tissue sections taken from paraffin blocks were stained with hematoxylin and eosin (H and E) and examined histopathologically under a light microscope. Intracellular H2O2 and apoptosis evaluations were carried out using the flow cytometric method. RESULTS: Sepsis caused a significant reduction in all sperm parameters. There was a significant decrease in sperm density, motility and cell numbers with normal morphology (p<0.05). Intracellular H2O2 level and apoptotic cell percentages increased in sperm cells in the CLP group. MEL treatment was found to significantly reduce sperm abnormalities, testicular damage, intracellular H2O2 levels, and apoptosis. CONCLUSION: This study showed that melatonin administration could be a potential treatment option to reduce acute testicular tissue damage due to sepsis.

Protective Effects of Platelet-rich plasma for in vitro Fertilization of Rats with Ovarian Failure Induced by Cyclophosphamide.

OBJECTIVE: Premature ovarian insufficiency (POI) contributes significantly to female infertility. Cyclophosphamide (CYC has adverse effects on folliculogenesis. Platelet-rich plasma (PRP) is an autologous product rich in many growth factors. We evaluated the protective effect of PRP on in vitro fertilization in female rats with CYC-induced ovarian damage. METHODS: Twenty-eight adult female Sprague-Dawley rats were randomly divided into four groups. Group 1 (control-sodium chloride 0.9%; 1 mL/kg, single-dose intraperitoneal [IP] injection); group 2 (CYC), 75 mg/kg, single-dose IP injection and sodium chloride 0.9% (1 mL/kg, single-dose IP injection); group 3 CYC plus PRP, CYC (75 mg/kg, single-dose and PRP (200 µl, single-dose) IP injection); and group 4 (PRP, 200 µl, single-dose IP injection). RESULTS: In the comparisons in terms of M1 and M2 oocytes, it was observed that the CYC group presented a significantly lower amount than the control, CYC/PRP, and PRP groups. (for M1, p = 0.000, p = 0.029, p = 0.025; for M2, p = 0.009, p = 0.004, p = 0.000, respectively). The number of fertilized oocytes and two-celled good quality embryos was found to be statistically significant between the CYC and control groups, CYC + PRP and PRP groups (p = 0.009, p = 0.001, p = 0.000 for oocytes, respectively. For embryos; p = 0.016, p = 0.002, p = 0.000). CONCLUSION: Platelet-rich plasma can protect the ovarian function against damage caused by CYC, and, in addition, it improves oocyte count and the development of embryos as a result of oocyte stimulation during the IVF procedure.

OBJETIVO: A insuficiência ovariana prematura (POI) contribui significativamente para a infertilidade feminina. A ciclofosfamida (CYC) tem efeitos adversos na foliculogênese. O plasma rico em plaquetas (PRP) é um produto autólogo rico em muitos fatores de crescimento. Avaliamos o efeito protetor do PRP na fertilização in vitro em ratas com lesão ovariana induzida por CYC. MéTODOS: Vinte e oito ratas Sprague-Dawley adultas foram divididas aleatoriamente em quatro grupos. Grupo 1 (controle - cloreto de sódio 0,9%; 1 mL/kg, injeção intraperitoneal [IP] em dose única); grupo 2 (CYC), 75 mg/kg, injeção IP de dose única e cloreto de sódio 0,9% (1 mL/kg, injeção ip de dose única); grupo 3 CYC + PRP, CYC (75 mg/kg, dose única e PRP (200 µl, dose única) injeção IP); e grupo 4 (PRP, 200 µl, injeção IP de dose única). RESULTADOS: Nas comparações em termos de ovócitos M1 e M2, observou-se que o grupo CYC apresentou uma quantidade significativamente menor que os grupos controle, CYC/PRP, e PRP. (Para M1, p = 0,000, p = 0,029, p = 0,025; para M2, p = 0,009, p = 0,004, p = 0,000, respectivamente). O número de oócitos fertilizados e embriões bicelulares de boa qualidade foi considerado estatisticamente significativo entre os grupos CYC e controle, CYC + PRP e grupos PRP (p = 0,009, p = 0,001, p = 0,000 para oócitos, respectivamente. Para embriões, p = 0,016, p = 0,002, p = 0,000). CONCLUSãO: O PRP pode proteger a função ovariana contra os danos causados pelo CYC e, além disso, proporciona melhora na contagem de oócitos e no desenvolvimento de embriões como resultado da estimulação ovariana durante o procedimento de fertilização in vitro.

Therapeutic effects of apocynin on ovarian ischemia-reperfusion induced lung injury.

Ovarian ischemia-reperfusion (I-R) injury may damage remote organs, including the lungs. We investigated whether apocynin, a NADPH oxidase inhibitor, might protect against ovarian I-R induced apoptosis in the lungs of rats. Bilateral ovarian I-R was induced for 3 h, then apocynin was applied at two concentrations. Lung tissue was evaluated using spectrophotometric and immunohistochemical methods. We found that I-R increased total oxidant status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) levels, and immunostaining of nuclear factor kappa-B (NF-κB), light chain 3B (LC3B), interleukin 1-beta (IL-1ß), caspase-3 and tumor necrosis factor-alpha (TNF-α), but decreased superoxide dismutase (SOD) values. Apocynin application to I-R injured rats enhanced recovery of lung tissue oxidants and improved both histology and frequency of apoptosis.

Urapidil alleviates ovarian torsion detorsion injury via regulating oxidative stress, apoptosis, autophagia, and inflammation.

OBJECTIVES: This study aimed to determine anti-inflammatory, antioxidant, and antiapoptotic properties of urapidil (Ura) against ovarian torsion detorsion (T/D) injury in rats. MATERIALS AND METHODS: 40 female Wistar albino rats were grouped as sham, T/D, T/D+dimethyl sulfoxide (DMSO), T/D+Urapidil (Ura) 0.5 mg/kg (low dose), and T/D+Urapidil (Ura) 5 mg/kg (high dose) groups. In treatment groups, Ura was administered intraperitoneally just before detorsion. Biochemical parameters (TAS, TOS, MDA, MPO, and SOD) and immunohistochemical (IL-1ß, TNF-α, NF-κB, LC3B, and Caspase-3) analyzes were performed. RESULTS: In the T/D group, OSI and MPO levels were elevated significantly while TAS values decreased compared with the sham group. A significant difference occurred in the low dose treatment group in TAS and OSI levels compared with the T/D group. In the high dose treatment group, significant elevation in TAS but reduction in OSI and MDA levels were observed compared with the T/D group. Immunohistochemical staining resulted in IL-1ß, TNF-α, NF-κB, LC3B, and caspase-3 immunopositivity in the T/D group, while Ura treatment decreased those parameters. Intensive congestion and hemorrhage were observed in the T/D group, but contrary to this, treatment groups had alleviated congestion and hemorrhage. CONCLUSION: These results suggest that Ura demonstrated protective effects against ovarian T/D injury via anti-oxidative, anti-inflammatory, and anti-apoptotic features.

Investigation of the effect of melatonin administration on inflammatory mediators; MMP-2, TGF-ß and VEGF levels in rats with sepsis.

AIMS: Sepsis causes life-threatening tissue and organ dysfunctions caused by endogenous mediators in response to infection. Melatonin is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. This study aimed to evaluate the changes in serum and liver tissue levels of VEGF, TGF-ß and MMP-2 in melatonin-treated septic rats. MATERIALS AND METHODS: Twenty-one Wistar-albino male rats were included in this study. Rats were randomly divided into three groups. Group 1 is sham-operated control (C) group, Group 2 is caecal ligation and puncture (CLP) group and Group 3 is melatonin-treated (10 mg/kg) (M-CLP) group. Serum and tissue samples were analysed. All procedures were carried out according to the ethical rules specified in Helsinki Declaration. RESULTS: Sera MMP-2 levels were found higher than tissue MMP-2 levels in C and CLP (respectively, P = .048, P = .01). In CLP and M-CLP, serum TGF-ß levels were higher than tissue TGF-ß levels(respectively, P = .05, P = .01). Serum VEGF levels in CLP were found to be significantly higher than both C and M-CLP(P < .01). CONCLUSION: MMP-2 levels may have increased because of the prevention of oxidative damage in sepsis, and this may increase the anti-inflammatory effect. Melatonin treatment may have a therapeutic effect against sepsis since it prevents the increase in serum VEGF level. A powerful endogenous antioxidant, may be a promising therapeutic agent on the mortality and morbidity of the disease, because of its lowering effect on serum VEGF, which is a poor prognostic factor in sepsis.

Atrial natriuretic peptide and posterior pituitary neurohormone changes in patients with acute schizophrenia.

OBJECTIVES: Interactions between neuropeptides and psychiatric disorders have been investigated for many years. The aim of this study was to evaluate oxytocin (OXT), arginine-vasopressin (AVP), and atrial natriuretic peptide (ANP) and assess their interactions with each other, as well as investigate these changes with the manifestations of schizophrenia. PARTICIPANTS AND METHODS: Thirty-four individuals having acute schizophrenia and 24 healthy individuals as the control group were included in the study. Positive and Negative Syndrome Scales, Global Assessment of Functionality score, and Clinical Global Impression (CGI) scores were measured. Serum hormone levels were analyzed using enzyme-linked immunosorbent assay and were compared with the clinical findings. RESULTS: OXT levels were significantly lower and AVP levels were significantly higher in patients having acute schizophrenia than the control group. OXT was negatively correlated with Positive and Negative Syndrome Scales positive score and CGI score, while it was positively correlated with Global Assessment of Functionality score. AVP was negatively correlated with CGI score. ANP levels of the patients having schizophrenia were lower than the control group; however, there was no significant correlation with clinical findings. CONCLUSION: The obtained data indicate that the AVP level was higher, but OXT and ANP levels were lower in the patients having acute schizophrenia. Specifically OXT is related with reduced disease severity and increased functionality.

Relationship of serum paraoxonase enzyme activity and thermal burn injury.

OBJECTIVE: This study investigated changes in serum oxidative stress parameters in burn cases compared to healthy controls. MATERIALS AND METHODS: This study was performed in 41 burn patients with mild to severe thermal burn injuries and 38 healthy volunteers. The burn cases were selected from patients who were hospitalized in the burn unit for the treatment of second- and third-degree burns. Malondialdehyde (MDA) levels and PON-1 paraoxonase and arylesterase activities were measured in patient serum samples. RESULTS: PON-1 paraoxonase activity and MDA levels in patients with major thermal burn injury were significantly higher than healthy controls, but PON-1 arylesterase activities were lower. A significant negative correlation was observed between the burn percentage of the total body surface area and the PON-1 arylesterase activities in patients. CONCLUSION: Human thermal burn injury was associated with an increase in MDA production and a decrease in PON-1 arylesterase activity, which was proportional to the percentage of total burned surface area.