Fisetin ameliorates methotrexate induced liver fibrosis.

OBJECTIVE: Methotrexate (MTX), a widely used chemotherapeutic and immunosuppressive agent, is associated with hepatotoxicity, leading to liver fibrosis and cirrhosis. This study explores the regenerative and reparative effects of fisetin, a flavonoid with known antioxidant and anti-inflammatory properties, on MTX-induced liver fibrosis in a rat model. MATERIALS AND METHODS: Thirty-six male Wistar albino rats were divided into normal, MTX and saline, and MTX and fisetin. Liver injury was induced in the latter two groups using a single intraperitoneal dose of MTX (20 mg/kg). Fisetin (50 mg/kg/day) or saline was administered intraperitoneally for ten days. After sacrifice, liver tissues were subjected to histopathological evaluation and biochemical analyses, including Transforming Growth Factor-ß1 (TGF-beta), sirtuins-1 (SIRT-1), malondialdehyde (MDA), cytokeratin 18, thrombospondin 1, and alanine transaminase (ALT) levels. RESULTS: MTX administration significantly increased liver injury markers, including TGF-beta, MDA, cytokeratin 18, thrombospondin 1, and ALT, while reducing SIRT-1 levels. Fisetin treatment attenuated these effects, demonstrating its potential therapeutic impact. Histopathological analysis confirmed that fisetin mitigated MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. CONCLUSIONS: This study proves that fisetin administration can alleviate MTX-induced liver damage in rats. The reduction in oxidative stress, inflammation, and apoptosis, along with the histological improvements, suggests fisetin's potential as a therapeutic agent against MTX-induced hepatotoxicity. Further investigations and clinical studies are warranted to validate these findings and assess fisetin's translational potential in human cases of MTX-induced liver damage.

Evaluation of the healing and protective properties of adipose-derived mesenchymal stem cells from cisplatin-induced liver and kidney damage.

OBJECTIVE: The occurrence of nephrotoxicity and hepatotoxicity as a result of cisplatin administration is a major concern in clinical practice. This study examined the potential protective effects of administering mesenchymal stem cells (MSCs) on the renal and hepatic damage caused by cisplatin. Moreover, the study investigated the potential protective effects of administering Adipose-Derived Mesenchymal Stem Cells (ADMSC) to counteract the harmful effects of cisplatin-induced kidney and liver damage. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into three groups: normal control, cisplatin + saline, and cisplatin + ADMSC. Cisplatin was administered to induce toxicity, and ADMSC was administered intravenously as a potential therapeutic intervention. Biochemical parameters and histopathological changes were assessed in the kidney and liver tissues. Statistical analyses were performed using a one-way ANOVA. RESULTS: Cisplatin increased malondialdehyde (MDA), tumor necrosis factor alfa (TNF-alfa), IL-6, alanine transaminase (ALT), creatinine, Galectin-3, Tissue growth factor beta 1 (TGF-beta 1), compared to the normal control group. Cisplatin-MSC reduced these levels. Histopathology showed that cisplatin caused kidney tubular epithelial necrosis, luminal necrotic debris, tubular dilatation, interstitial inflammation, liver sinusoidal and central vein dilatation, congestion, necrosis, and cytoplasmic vacuolization. ADMSC administration significantly reduced histopathological changes. CONCLUSIONS: These findings highlight the potential therapeutic benefits of mesenchymal stem cell (MSC) administration in mitigating cisplatin-induced nephrotoxicity and hepatotoxicity. MSC treatment demonstrated protective effects by reducing oxidative stress, inflammatory markers, and histopathological alterations. Further investigations are warranted to elucidate the precise mechanisms underlying these protective effects and evaluate their clinical implications for managing cisplatin-induced organ damage.

Is near-infrared spectroscopy a promising predictor for early intracranial hemorrhage diagnosis in the Emergency Department?

Intracranial hemorrhage (ICH) is a serious medical condition that can lead to significant morbidity and mortality if not diagnosed and treated promptly. Early detection and treatment are essential for improving the outcome in patients with ICH. Near-infrared spectroscopy (NIRS) is a non-invasive imaging technique that has been used to detect changes in brain tissue oxygenation and blood flow in various conditions. The aim of this study was to investigate the predictive potential of NIRS for early diagnosis of ICH in patients presenting to the Emergency Department (ED) triage with headache. A total of 378 patients were included in the study. According to the final diagnosis of the patients, 4 groups were formed: migraine, tension-cluster headache, intracranial hemorrhage and intracranial mass, and control group. Cerebral NIRS values "rSO2" were measured at the first professional medical contact with the patient. The right and left rSO2 (RrSO2, LrSO2) were significantly lower and the rSO2 difference was significantly higher in the intracranial hemorrhage group compared to all other patient groups (P<0.001). The cut-off values determined in the receiver operating characteristics (ROC) analysis were RrSO2 ≤67, LrSO2 ≤67, and ΔrSO2 ≥9. This study found that a difference of more than 9 in cerebral right-left NIRS values can be a non-invasive, easy-to-administer, rapid, and reliable diagnostic test for early detection of intracranial bleeding. NIRS holds promise as an objective method in ED triage for patients with intracranial hemorrhage. However, further research is needed to fully understand the potential benefits and limitations of this method.

Is near-infrared spectroscopy a promising predictor for early intracranial hemorrhage diagnosis in the Emergency Department?

Intracranial hemorrhage (ICH) is a serious medical condition that can lead to significant morbidity and mortality if not diagnosed and treated promptly. Early detection and treatment are essential for improving the outcome in patients with ICH. Near-infrared spectroscopy (NIRS) is a non-invasive imaging technique that has been used to detect changes in brain tissue oxygenation and blood flow in various conditions. The aim of this study was to investigate the predictive potential of NIRS for early diagnosis of ICH in patients presenting to the Emergency Department (ED) triage with headache. A total of 378 patients were included in the study. According to the final diagnosis of the patients, 4 groups were formed: migraine, tension-cluster headache, intracranial hemorrhage and intracranial mass, and control group. Cerebral NIRS values "rSO2" were measured at the first professional medical contact with the patient. The right and left rSO2 (RrSO2, LrSO2) were significantly lower and the rSO2 difference was significantly higher in the intracranial hemorrhage group compared to all other patient groups (P<0.001). The cut-off values determined in the receiver operating characteristics (ROC) analysis were RrSO2 ≤67, LrSO2 ≤67, and ΔrSO2 ≥9. This study found that a difference of more than 9 in cerebral right-left NIRS values can be a non-invasive, easy-to-administer, rapid, and reliable diagnostic test for early detection of intracranial bleeding. NIRS holds promise as an objective method in ED triage for patients with intracranial hemorrhage. However, further research is needed to fully understand the potential benefits and limitations of this method.

Oxytocin mitigates peripheral nerve damage via Nrf2 and irisin pathway.

OBJECTIVE: Peripheral nerve injuries present challenges in achieving full functional restoration, necessitating effective therapeutic strategies. Oxytocin, known for its neuroprotective and anti-inflammatory properties, has shown potential in nerve recovery. This study aims to elucidate the role of oxytocin in nerve recovery via the nuclear factor erythroid 2-related factor 2 (Nrf2) and irisin pathways. MATERIALS AND METHODS: Adult male Wistar rats (n=30) were subjected to surgical dissection of sciatic nerves and divided into Control, Surgery and Saline Group, and Surgery and Oxytocin (OT) group. Electromyographic (EMG) recordings, inclined plane tests, and histological assessments were conducted to evaluate nerve function, and Nerve growth factor (NGF) immunoexpression and axonal parameters were measured. Plasma irisin levels, nerve NGF, and Nrf2 levels were quantified. RESULTS: The Surgery and Saline Group exhibited impaired EMG latency, amplitude, and inclined plane score compared to Controls, while the Surgery and OT Group demonstrated improved outcomes. Histomorphometric analysis revealed increased NGF immunoexpression, axon number, diameter, and reduced fibrosis in the Surgery and OT Group. Plasma irisin levels were higher following oxytocin administration. Additionally, nerve NGF and Nrf2 levels were elevated in the Surgery and OT Group. CONCLUSIONS: OT administration mitigated nerve injury effects, promoting functional and histological improvements. Elevated NGF and Nrf2 levels, along with increased irisin, indicated the potential interplay of these pathways in enhancing nerve recovery. The results align with OT's neuroprotective and anti-inflammatory roles, suggesting its potential as a therapeutic intervention for nerve injuries. OT's positive impact on nerve recovery is associated with its modulation of Nrf2 and irisin pathways, which collectively enhance antioxidant defense and neurotrophic support and mitigate inflammation. These findings underline OT's potential as a therapeutic agent to enhance nerve regeneration and recovery. Further research is needed to elucidate the intricate molecular mechanisms and potential clinical applications of OT in nerve injury management.

Anti-inflammatory and antioxidant properties of betaine protect against sepsis-induced acute lung injury: CT and histological evidence.

The aim of this research was to determine the anti-inflammatory effect of betaine on sepsis-induced acute respiratory distress syndrome (ARDS) in rats through histopathological examination, radiologic imaging, and biochemical analysis. Eight rats were included in the control group, and no procedure was performed. Feces intraperitoneal procedure (FIP) was performed on 24 rats to create a sepsis-induced ARDS model. These rats were separated into three groups as follows: FIP alone (sepsis group, n=8), FIP + saline (1 mL/kg, placebo group, n=8), and FIP + betaine (500 mg/kg, n=8). Computed tomography (CT) was performed after FIP, and the Hounsfield units (HU) value of the lungs was measured. The plasma levels of tumor necrosis factor (TNF)-α, interleukin-1ß (IL-1ß), IL-6, C-reactive protein, malondialdehyde (MDA), and lactic acid (LA) were determined, and arterial oxygen pressure (PaO2) and arterial CO2 pressure (PaCO2) were measured from an arterial blood sample. Histopathology was used to evaluate lung damage. This study completed all histopathological and biochemical evaluations in 3 months. All evaluated biomarkers were decreased in the FIP + betaine group compared to FIP + saline and FIP alone (all P<0.05). Also, the parenchymal density of the rat lung on CT and histopathological scores were increased in FIP + saline and FIP alone compared to control and these findings were reversed by betaine treatment (all P<0.05). Our study demonstrated that betaine suppressed the inflammation and ameliorated acute lung injury in a rat model of sepsis.

Anti-inflammatory and antioxidant properties of betaine protect against sepsis-induced acute lung injury: CT and histological evidence

The aim of this research was to determine the anti-inflammatory effect of betaine on sepsis-induced acute respiratory distress syndrome (ARDS) in rats through histopathological examination, radiologic imaging, and biochemical analysis. Eight rats were included in the control group, and no procedure was performed. Feces intraperitoneal procedure (FIP) was performed on 24 rats to create a sepsis-induced ARDS model. These rats were separated into three groups as follows: FIP alone (sepsis group, n=8), FIP + saline (1 mL/kg, placebo group, n=8), and FIP + betaine (500 mg/kg, n=8). Computed tomography (CT) was performed after FIP, and the Hounsfield units (HU) value of the lungs was measured. The plasma levels of tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), IL-6, C-reactive protein, malondialdehyde (MDA), and lactic acid (LA) were determined, and arterial oxygen pressure (PaO2) and arterial CO2 pressure (PaCO2) were measured from an arterial blood sample. Histopathology was used to evaluate lung damage. This study completed all histopathological and biochemical evaluations in 3 months. All evaluated biomarkers were decreased in the FIP + betaine group compared to FIP + saline and FIP alone (all P<0.05). Also, the parenchymal density of the rat lung on CT and histopathological scores were increased in FIP + saline and FIP alone compared to control and these findings were reversed by betaine treatment (all P<0.05). Our study demonstrated that betaine suppressed the inflammation and ameliorated acute lung injury in a rat model of sepsis.

The effect of sulfasalazine in pentylenetetrazole-induced seizures in rats.

We aimed to reveal the anti-convulsant effects sulfasalazine and its mechanism in pentylenetetrazole (PTZ)-induced seizures in rats. Forty-eight male Wistar albino rats (200-250 g) were randomly divided into two groups: 24 for electroencephalography (EEG) recording (group A) and 24 for behavioral studies (group B). About 70 mg/kg PTZ was used for behavioral studies after sulfasalazine administration and 35 mg/kg PTZ was used for EEG recording after sulfasalazine administration. Electrodes were implanted on the dura mater over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. Racine's convulsion scale, first myoclonic jerk onset time, spike percentages, brain malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin F2α (PGF2α) levels were evaluated between the groups. First myoclonic jerk onset time was significantly shorter in the saline group than both 250 and 500 mg/kg sulfasalazine groups (P<0.05). Racine's convulsion scores were significantly lower in the 250 and 500 mg/kg sulfasalazine groups than the saline group (P<0.05, P<0.001). The two sulfasalazine groups had lower spike percentages than the saline group (P<0.05). Significantly lower MDA and PGF2α levels were observed in the 250 and 500 mg/kg sulfasalazine groups compared with the saline group (P<0.05, P<0.001, respectively). SOD increased significantly in both sulfasalazine groups compared with the PTZ+saline group (P<0.05). Our study demonstrated that sulfasalazine had protective effects on PTZ-induced convulsions by protecting against oxidative and inflammatory damage associated with PTZ.

The effect of sulfasalazine in pentylenetetrazole-induced seizures in rats

We aimed to reveal the anti-convulsant effects sulfasalazine and its mechanism in pentylenetetrazole (PTZ)-induced seizures in rats. Forty-eight male Wistar albino rats (200-250 g) were randomly divided into two groups: 24 for electroencephalography (EEG) recording (group A) and 24 for behavioral studies (group B). About 70 mg/kg PTZ was used for behavioral studies after sulfasalazine administration and 35 mg/kg PTZ was used for EEG recording after sulfasalazine administration. Electrodes were implanted on the dura mater over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. Racine's convulsion scale, first myoclonic jerk onset time, spike percentages, brain malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin F2α (PGF2α) levels were evaluated between the groups. First myoclonic jerk onset time was significantly shorter in the saline group than both 250 and 500 mg/kg sulfasalazine groups (P<0.05). Racine's convulsion scores were significantly lower in the 250 and 500 mg/kg sulfasalazine groups than the saline group (P<0.05, P<0.001). The two sulfasalazine groups had lower spike percentages than the saline group (P<0.05). Significantly lower MDA and PGF2α levels were observed in the 250 and 500 mg/kg sulfasalazine groups compared with the saline group (P<0.05, P<0.001, respectively). SOD increased significantly in both sulfasalazine groups compared with the PTZ+saline group (P<0.05). Our study demonstrated that sulfasalazine had protective effects on PTZ-induced convulsions by protecting against oxidative and inflammatory damage associated with PTZ.