The effects of metyrosine on ischemia-reperfusion-induced oxidative ovarian injury in rats: Biochemical and histopathological assessment.

The aim of this study is to investigate the effect of metyrosine on ischemia-reperfusion (I/R) induced ovarian injury in rats in terms of biochemistry and histopathology. Rats were divided into: ovarian I/R (OIR), ovarian I/R+50 mg/kg metyrosine (OIRM) and sham (SG) operations. OIRM group received 50 mg/kg metyrosine one hour before the application of the anesthetic agent, OIR and SG group rats received equal amount of distilled water to be used as a solvent orally through cannula. Following the application of the anesthetic agent, ovaries of OIRM and OIR group rats were subjected to ischemia and reperfusion, each of which took two hours. This biochemical experiment findings revealed high levels of malondialdehyde (MDA) and cyclo-oxygenase-2 (COX-2) and low levels of total glutathione (tGSH), superoxide dismutase (SOD) and cyclo-oxygenase-1 (COX-1) in the ovarian tissue of OIR group, with significant histopathological injury. In metyrosine group, MDA and COX-2 levels were lower than the OIR group whereas tGSH, SOD and COX-1 levels were higher, with slighter histopathological injury. Our experimental findings indicate that metyrosine inhibits oxidative and pro-inflammatory damage associated with ovarian I/R in rats. These findings suggest that metyrosine could be useful in the treatment of ovarian injury associated with I/R.

High Serum Progranulin Levels in COVID-19 Patients: A Pilot Study.

In this study, we aimed to determine whether the progranulin level in serum predicts the course and severity of the disease in COVID-19 (+) patients and whether it can be used as a biomarker in these patients. Therefore, we sampled 61 people infected with COVID-19, and the cases were divided into the following groups: asymptomatic, noncomplicated, moderate, and severe. Concentrations of progranulin, TNF-α, IL-6 from in serum obtained from all participants were measured using commercially available ELISA kits, as well as WBC, PLT, NE, LY, ALT, AST, Hb, PCT, and CRP were examined with clinical analyzer. All measurements obtained for the patient samples were compared with those of 20 healthy individuals. The serum progranulin concentration was statistically higher in the COVID-19 (+) patient group than in the control group of healthy individuals [112.6 ± 54.8, 0.0 (0.0-54.2 pg/ml, respectively p = 0.000)]. ROC analysis was performed to evaluate the progranulin potential as a biomarker for COVID-19 (+) patients. A larger AUC (0.931 ± 0.08) value and a more significant p-value for progranulin than for CRP (p = 0.000) was detected. As a result, we believe that progranulin reaches high levels in the COVID-19 disease and may be a determinant in diagnosis and prognosis, and may be a better biomarker than CRP.

Could Fetuin-A Be a Biomarker for Autism Spectrum Disorder and Cognitive Developmental Delay?

Early detection of cognitive developmental delay (CDD) and autism spectrum disorder (ASD) is challenging, despite the numerous scientific studies conducted and different therapeutic strategies. Lack of a biomarker for autism is a limiting factor for early diagnosis, which could provide better outcome with early start of therapy. Because of the high serum fetuin-A concentration during intrauterine life, it has been suggested that fetuin-A may have a role in brain development. The current study sought to determine if fetuin-A, a multifunctional glycoprotein thought to have a role in brain development, may be used as a biomarker for the diagnosis of ASD and developmental delay. The study involved 55 children with cognitive developmental delays and 40 healthy children. Two categories of children with cognitive developmental delays were identified. The participants were subjected to a psychiatric assessment as well as developmental testing. Only 54.5% of the 55 individuals had CDD, whereas 45.5% had ASD. Using an ELISA kit, the levels of serum fetuin-A were determined spectrophotometrically. The serum fetuin-A levels in the patients from the test group were found to be significantly lower than in the healthy individuals (p < 0.001). The cutoff value for the serum fetuin-A levels for cognitive developmental delay and autism spectrum disorder was 518 µg/liter, according to the results of ROC analysis (84.6% sensitivity and 91.4% specificity, AUC: 0.95, p < 0.001). The findings suggest that the serum fetuin-A level may be used to diagnose autism spectrum disorder and cognitive developmental delays.

The role of adropin, HIF-1α and apelin biomarkers in the diagnosis of acute mesentaric ischemia.

OBJECTIVE: The absence of a specific biomarker for acute mesenteric ischemia diagnosis results in a delay in diagnosis and treatment, as well as a high mortality rate. The current research examined whether the proteins adropin, HIF-1α, and apelin may be used to help in the early detection of acute mesenteric ischemia. MATERIALS AND METHODS: A total of 20 patients with acute mesenteric ischemia, 20 patients with abdominal pain, and 20 healthy controls were included in the study. The levels of adropin, HIF-1, and apelin in the serum were determined using the ELISA method. RESULTS: Adropin concentrations were significantly higher in the acute mesenteric ischemia group than in the abdominal pain and healthy control groups (p < 0.05). HIF-1α levels were considerably greater in patients with acute mesenteric ischemia compared to both the abdominal pain group and the healthy control group (p < 0.05). There was no difference in apelin levels between the acute mesenteric ischemia and abdominal pain groups (p > 0.05). HIF-1α was found to be moderate (AUC: 0.705) and adropin was found to be a weak biomarker (AUC: 0.692) in the ROC analysis for acute mesenteric ischemia. CONCLUSION: In this study of 20 patients with acute mesenteric ischemia, we found adropin and HIF-1α levels to be increased compared to patients with abdominal pain who did not have acute mesenteric ischemia.

Coenzyme Q10 effect on cisplatin-induced oxidative retinal injury in rats.

AIM: In this study, it was aimed to investigate the effect of coenzyme Q10 (CoQ10) on cisplatin-induced oxidative retinal damage in rats biochemically and histopathologically. MATERIALS AND METHODS: Thirty male Wistar albino rats were divided into 3 groups randomly: untreated control (C group), only 2.5 mg/kg cisplatin daily administrated group for 2 weeks (CP group), 2.5 mg/kg cisplatin + 20 mg/kg orally CoQ10 daily administrated group for 2 weeks (CoQC group). At the end of experimental period, blood samples obtained before sacrification for the biochemical examination of serum malondialdehyde (MDA), total glutathione (tGSH), total oxidant system (TOS), total antioxidant systemic (TAS) levels and after eyes were removed for examined histopathology. RESULTS: As a result of our study, severe histopathological damage was detected in the retinal tissue of the cisplatin group with serum malondialdehyde (MDA) and total oxidant system (TOS) levels were high and total glutathione (tGSH) and total antioxidant systemic (TAS) levels were low. However, it was observed that the histopathological damage associated with cisplatin was decreased in the retinal tissue of the CoQ10 group, which inhibited the increase in blood serum MDA/TOS levels and decrease in tGSH/TAS levels. CONCLUSION: The biochemical and histopathological results of our study were compatible with each other, so we concluded that the damage to the rat retinal tissue caused by cisplatin may be reversible with coenzyme.

Effect of taxifolin on cisplatin-associated oxidative optic nerve damage in rats.

AIM: To investigate the effect of taxifolin on cisplatin-induced oxidative and proinflammatory optic nerve damage in rats. METHODS: A total of 18 albino Wistar male rats were assigned into 3 groups, as follows; Group 1: Control group, Group 2: Only cisplatin administered group for 14 days (Cisplatin group), and Group 3: Taxifolin + cisplatin administered group for 14 days (CIS + TAX group). Serum malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-ƘB), Total Oxidative Status (TOS) and Total Antioxidant Status (TAS) levels were collected from the left eyes of rats. Rats' right eyes were enucleated for histopathological evaluations of optic nerves. RESULTS: NF-ƘB, MDA and TOS levels were statistically significantly higher (p < 0.001) in cisplatin group when compared to other 2 groups, the tGSH and TAS levels of which were statistically significantly lower (p < 0.001). Regarding these parameters, in cisplatin group NF-ƘB, MDA and TOS levels were statistically significantly increased with cisplatin administration and giving taxifolin concomitantly with cisplatin prevented this elevation. On the other hand, tGSH and TAS levels were statistically significantly decreased with cisplatin administration and routine simultaneous application of taxifolin with cisplatin prevented this decrease. In histopathological findings, haemorrhage was observed in the perineum of the injured optic nerves in the cisplatin treated group. And also edoema and degeneration in nerve fascicles in damaged optic nerves were seen in the cisplatin group. In the taxifolin treated group histopathological examinations were close to normal appearance, except mild edoema in nerve fascicles. CONCLUSION: Cisplatin causes oxidative stress on the rat optic nerves, and these changes lead to significant histopathological damage. Taxifolin, which we used to prevent oxidative damage to the optic nerves caused by cisplatin, has been emphasized as a powerful antioxidant agent in many previous scientific investigations. Concomitant administration of taxifolin may prevent these adverse effects of cisplatin, as well as histopathological damage. Further studies are needed to fully determine the effects of cisplatin and taxifolin on the eye.

Effect of Rutin on Cytarabine-Associated Pulmonary Oedema and Oxidative Stress in Rats.

Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.

The effects of lutein on optic nerve injury induced by ethambutol and isoniazid: an experimental study.

AIM: Ethambutol and isoniazid are two major effective first line agents in tuberculosis treatment having some visual adverse effects. We aimed to determine the protective effects of lutein on oxidative optic neuropathy induced by ethambutol and isoniazid in an experimental model. MATERIAL AND METHOD: Totally 24 albino Wistar male rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), 50 mg/kg ethambutol +50 mg/kg isoniazid administered group (EI), 0.5 mg/kg lutein +50 mg/kg ethambutol +50 mg/kg isoniazid administered group (LEI-05) and only Lutein (0.5 mg/kg) (LUT group) administered group. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), total glutathione (GSH), interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed at the end of the study. RESULTS: Serum and tissue IL-1ß, TNF-α and MDA levels were the highest in EI group which were significantly lower in lutein administered group. On the other hand, serum and tissue total GSH levels were the lowest in EI group which were significantly higher in Lutein administered group. In histopathological evaluations, there were significant differences between EI group and all other three groups with edema and hemorrhage in connective tissue covering optic nerve, dilated and congested capillary, decrease in astrocytes and oligodendrocytes. CONCLUSION: Isoniazid and ethambutol induced toxic optic neuropathy although not common, may have some potential devastating effects on vision. Lutein is determined as an effective agent in prevention of isoniazid and ethambutol induced toxic optic neuropathy.

The effect of rutin on ovarian ischemia-reperfusion injury in a rat model.

The effect of rutin on ovarian ischemia-reperfusion (I/R) injury was investigated in this experimental study. Eighteen Wistar albino female rats were divided into three groups as follows: I/R group (IRG; n = 6), 50 mg/kg rutin + I/R group (RG; n = 6), and a healthy control group scheduled for a sham operation (SG; n = 6). 2 h of ischemia and following 2 h of reperfusion were created in the IRG and RG by using a torsion model involving atraumatic vascular clips. Rutin, a flavonoid glycoside, was injected intraperitoneally at the dose of 50 mg/kg to RG group 1 h before reperfusion. Then, rats were euthanized and their ovaries were removed for biochemical and histopathological examination and also assessment of the gene expressions. IRG group had a significant increase in malondialdehyde (MDA) levels, in the expressions of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), and also in the activity of cyclooxygenase 2 (COX-2) unlike the significant decrease in total glutathione (tGSH) levels and the activity of COX-1 when compared to the SG group. However, rutin significantly decreased MDA levels, the expressions of TNF-α and IL-1ß, and also the activity of COX-2 while it increased significantly tGSH levels and the activity of COX-1 in the RG group in comparison with the IRG group. Rutin ameliorated the I/R-induced ovarian injury in rats via its possible antioxidative and anti-inflammatory effects.

The effects of lutein on cisplatin-induced retinal injury: an experimental study.

AIM: Lutein is one of the most common carotenoids defined in human plasma as having potent anti-oxidant effects. We aimed to determine the biochemical and histopathological effects of lutein on cisplatin-induced oxidative retinal injury in rats. MATERIALS AND METHODS: Twenty-four rats were equally divided into four groups as healthy controls (HC group), only cisplatin (5 mg/kg) administered group (CIS group), Lutein (0.5 mg/kg) + cisplatin (5 mg/kg) administered group (LC group), and only Lutein (0.5 mg/kg) (LUT group) administered group. From the blood samples obtained, serum malondialdehyde (MDA), total glutathione (tGSH), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α) levels were investigated. In histopathological analyses, the total retinal thickness, retinal pigment epithelium (RPE), photoreceptor layer (PL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL) were evaluated. RESULTS: MDA, IL-1ß, and TNF-a levels were statistically significantly higher (p < 0.001) in CIS group compared with other three groups while tGSH levels were statistically significantly lower (p < 0.001). In subgroup analyses, there was no any statistically significant difference regarding all four parameters analyzed between HC, LC, and LUT groups. In histopathological analyses, cisplatin-induced retinal damage included atrophy and disorganization on outer segment, degeneration and detachment of RPE and PL from choroid, degeneration and edema of INL and IPL, total degeneration of GCL; while cisplatin-induced retinal damage was determined to be significantly prevented with 0.5 mg lutein treatment on histopathological evaluations. CONCLUSIONS: Lutein co-administration was highly effective in prevention of cisplatin-induced retinal damage due to the anti-oxidant and anti-inflammatory effects of lutein.

The effects of rutin on cisplatin induced oxidative retinal and optic nerve injury: an experimental study.

AIM: To determine the role of rutin in prevention of cisplatin induced retinal and optic nerve injury in an experimental study. MATERIALS AND METHODS: Totally 18 albino Wistar male rats were assigned into three groups, as follows: healthy controls (HC group), only cisplatin administered group for 14 days (CIS group), and rutin + cisplatin administered group for 14 days (RC group). Blood samples were obtained from animals just before the scarification. Serum malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), superoxide dismutase (SOD), interleukin 1 beta (IL-1ß) and tumour necrosis factor alpha (TNF-α) levels were investigated. The eyes were enucleated for histopathological evaluations of retina and optic nerve. RESULTS: MDA, MPO, IL-1ß and TNF-α levels were statistically significantly higher (p < 0.001) in CIS group compared with other two groups while tGSH and SOD levels were statistically significantly lower (p < 0.001). Regarding these parameters, in CIS group MDA, MPO, IL1ß and TNF-α levels were statistically significantly increased with cisplatin administration and giving rutin concomitantly with cisplatin prevented this increase. On the other hand, tGSH and SOD levels were statistically significantly decreased with cisplatin administration and giving rutin concomitantly with cisplatin prevented this decrease. In qualitative analyses of histopathological findings of retina and optic nerve; the results of RC group were similar with the results of healthy controls; but there was statistically significant differences between CIS group and other two groups (p < 0.001). CONCLUSIONS: Concomitant rutin administration may prevent the detrimental effects of cisplatin on lipid peroxidation, oxidative stress and inflammation markers and may also avert the histopathological damage on retina and optic nerve. Further studies are warranted to determine the effects of cisplatin and rutin on eye.

Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia.

Iron deficiency anemia (IDA) is a major public health problem especially in underdeveloped and developing countries. Zinc is the co-factor of several enzymes and plays a role in iron metabolism, so zinc deficiency is associated with IDA. In this study, it was aimed to investigate the relationship of symptoms of IDA and zinc deficiency in adult IDA patients. The study included 43 IDA patients and 43 healthy control subjects. All patients were asked to provide a detailed history and were subjected to a physical examination. The hematological parameters evaluated included hemoglobin (Hb); hematocrit (Ht); red blood cell (erythrocyte) count (RBC); and red cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (МСН), mean corpuscular hemoglobin concentration (МСНС), and red cell distribution width (RDW). Anemia was defined according to the criteria defined by the World Health Organization (WHO). Serum zinc levels were measured in the flame unit of atomic absorption spectrophotometer. Symptoms attributed to iron deficiency or depletion, defined as fatigue, cardiopulmonary symptoms, mental manifestations, epithelial manifestations, and neuromuscular symptoms, were also recorded and categorized. Serum zinc levels were lower in anemic patients (103.51 ± 34.64 µ/dL) than in the control subjects (256.92 ± 88.54 µ/dL; <0.001). Patients with zinc level <99 µ/dL had significantly more frequent mental manifestations (p < 0.001), cardiopulmonary symptoms (p = 0.004), restless leg syndrome (p = 0.016), and epithelial manifestations (p < 0.001) than patients with zinc level > 100 µ/dL. When the serum zinc level was compared with pica, no statistically significant correlation was found (p = 0.742). Zinc is a trace element that functions in several processes in the body, and zinc deficiency aggravates IDA symptoms. Measurement of zinc levels and supplementation if necessary should be considered for IDA patients.

The role of antioxidant activity in the prevention and treatment of infertility caused by Cisplatin in rats.

BACKGROUND/AIMS: To investigate the importance of antioxidant activity in infertility caused by cisplatin in rats. METHODS: Rats in cisplatin control (CG), Vitamin E + cisplatin (ECG), Vitamin C + cisplatin (CCG), Hippophae rhamnoides extract (HRE) + cisplatin (HRECG), and thiamine pyrophosphate (TPP) + cisplatin (TPPCG) groups were injected intraperitoneally (ip) with (100 mg/kg) Vitamin E, Vitamin C, HRE, and TPP, respectively. One hour later, ip cisplatin was administered (5 mg/kg), and then antioxidant medications were continued for 10 days. Cisplatin + Vitamin E (CEG-1), cisplatin + Vitamin C (CCG-1), cisplatin + HRE (CHREG-1), and cisplatin + TPP (TPPCG-1) rats received cisplatin (5 mg/kg, ip) and were kept for 10 days. At the end of that period, rats received antioxidant medications for 10 days. (n = 12, for each group). Six rats from each group were sacrificed. Ovaries were removed to measure malondialdehyde, total glutathione, glutathione S-transferase, and glutathione reductase levels. The remaining rats were kept in a suitable laboratory environment. RESULTS: Cisplatin-induced oxidative stress was best prevented by HRE, Vitamin E, Vitamin C, and TPP, in that order. However, infertility caused by cisplatin was only prevented and treated by TPP. CONCLUSION: Oxidative stress is not a major component in the pathogenesis of cisplatin-associated infertility.

The effect of nimesulide on oxidative damage inflicted by ischemia-reperfusion on the rat renal tissue.

The objective of our study is to research biochemically and histopathologically the effect of nimesulide on oxidative damage inflicted by ischemia-reperfusion (I/R) on the rat renal tissue. Twenty-four albino Wistar type of male rats were used for the experiment. The animals were divided into groups as: renal ischemia-reperfusion control (RIR), nimesulide+renal ischemia-reperfusion of 50 mg/kg (NRIR-50), nimesulide+renal ischemia-reperfusion of 100 mg/kg (NRIR-100), and sham groups (SG). In NRIR-50 and NRIR-100 groups were given nimesulide, and RIR and SG groups were given distilled water, an hour after anesthesia. Groups, except for the SG group, 1-h-ischemia and then 6-h-reperfusion were performed. In the renal tissue of the RIR group in which the malondialdehyde (MDA), myeloperoxidase (MPO), and 8-hydroxyguanine (8-OHGua) levels were measured, the COX-1 and COX-2 activities were recorded. Nimesulide at 100 mg/kg doses reduced the oxidant parameters more significantly than 50 mg/kg doses; on the other hand, it raised the antioxidant parameters. It has been shown that 100 mg/kg doses of nimesulide prevented the renal I/R damage more significantly than a dose of 50 mg/kg, which shows that nimesulide, in clinics, could be used in the prevention of I/R damage.

Evaluation of the salivary levels of visfatin, chemerin, and progranulin in periodontal inflammation.

OBJECTIVES: In recent years, adipokines have been reported to play an important role in chronic inflammatory diseases. In this study, our aim was to investigate the salivary levels of visfatin, chemerin, and progranulin and their relationship with periodontal health and disease. MATERIALS AND METHODS: A total of 72 patients were included in the study, 23 of which were periodontally healthy, 24 had gingivitis, and 25 had periodontitis. The clinical periodontal parameters including plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment levels (CAL) were recorded. Unstimulated saliva samples were collected, and the concentration of adipokines was evaluated using standard enzyme-linked immunosorbent assay. RESULTS: Salivary visfatin levels were higher in patients with gingivitis and periodontitis compared to those of healthy subjects, while there was no difference between the mean values of gingivitis and periodontitis groups (P > 0.05). There was no difference between the mean values of gingivitis and healthy groups regarding salivary chemerin (P > 0.05), whereas it was detected at higher levels in the periodontitis group compared to the gingivitis and the healthy groups (P < 0.01). Salivary progranulin levels were similar in all groups (P > 0.05). The salivary visfatin level was positively related to PI and GI. The salivary chemerin level was positively related to GI, PD, and CAL. CONCLUSIONS: These results demonstrated that the higher levels of chemerin in the saliva of patients with periodontitis were correlated with the degree of tissue destruction. CLINICAL RELEVANCE: Chemerin may be a novel biomarker in saliva to determine the severity of periodontal disease.

Quantification of Heavy Metals in the Nasal Turbines of Smokers and Nonsmokers.

OBJECTIVES: Cigarette smoke is known to contain toxic heavy metals. In this study, heavy metal levels in the nasal turbinate tissues of smokers and nonsmokers were measured and compared with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). METHODS: Forty patients who come to the Otorhinolaryngology outpatient clinic due to nasal obstruction and are given an appointment for partial turbinate reduction operation due to inferior turbinate hypertrophy, according to their smoking status, were divided into two groups: those who had smoked one pack/day for at least 10 years and those who had never smoked. The levels of heavy metals (Al, As, Ba, Cd, Cr, Co, Cu, Pb, Mn, Hg, Ni, Se, and Ag) were compared by ICP-MS in nasal turbinate tissues. RESULTS: Al (p = 0.002), Cr (p < 0.001), Co (p < 0.001), Ni (p = 0.001), Cu (p < 0.001), As (p < 0.001), Se (p < 0.001), Ag (p < 0.001), Cd (p = 0.001), Ba (p = 0.008), Hg (p < 0.001), and Pb (p < 0.001) values in the smoker group were found to be significantly higher than the values of nonsmokers. Although the Mn level was high in smokers, no significant difference was observed (p = 0.299). CONCLUSIONS: Smoking can cause nasal and sinus problems. In this study, we observed that the smoking group had significantly higher levels of almost all the heavy metals investigated in the nasal turbinate tissues. As smoking damages, the mucociliary system and the mucosa, heavy metals from cigarettes may accumulate further and cause harm to the nasal tissues. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3562-3567, 2024.

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.

C-terminal cross-linking telopeptide levels in COVID-19 patients: A prospective case-control study.

BACKGROUND: Coronavirus disease 19 (COVID-19) is a viral infection mediated by coronavirus-2 that causes severe acute respiratory syndrome (SARS-CoV-2). The disease may affect biochemical parameters and electrolytes. C-terminal cross-linking telopeptide (CTX-I) is released during mature bone resorption and is a biomarker for predicting bone resorption. OBJECTIVES: As the pandemic progressed, understanding the effects of COVID-19 disease remained critical. Inflammatory responses triggered by the virus can result in a bone metabolism regulation imbalance. As such, this study aimed to analyze serum levels of CTX-I, calcium (CA), phosphorus (P), magnesium (Mg), C-reactive protein (CRP), and alkaline phosphatase (ALP) in COVID-19 patients to investigate the relationship between bone resorption and the disease. MATERIAL AND METHODS: The study included 56 individuals with COVID-19 (divided into mild, moderate and severe subgroups depending on disease severity) and 25 healthy adults as a control group. Serum CTX-I concentrations were measured with enzyme-linked immunosorbent assay (ELISA). In addition, CRP, Ca, Mg, P, and ALP levels were measured using an automated clinical chemistry analyzer. RESULTS: Serum CTX-I levels were significantly higher in COVID-19 patients than in the control group (p < 0.05). Furthermore, a positive weak relationship was detected between CRP and CTX-I (r = 0.303, p < 0.05). CONCLUSIONS: Increased serum CTX-I levels in the patient group caused COVID-19-driven bone degradation, though serum CTX-I levels did not differ according to disease severity.

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.