Determination of anti-cancer effects of Nigella sativa seed oil on MCF7 breast and AGS gastric cancer cells.

BACKGROUND: This study aimed to investigate the cytotoxic, apoptotic, invasion, metastasis, and heat shock proteins (HSPs) effects of N. sativa oil on breast and gastric cancer cells. METHODS: We assessed the cytotoxic and apoptotic effects of various concentrations of N. sativa oil (10-50-100-200 µg/mL) on MCF7 breast cancer and AGS, an adenocarcinoma of the gastric cell line, at 24, 48 and 72 h using the MTT test. Additionally, the expression of the Caspase-3, BCL2/Bax, MMP2-9 and HSP60-70 gene was examined using RT-PCR in cell lines treating with N. sativa. RESULTS: The MTT experiments demonstrate that N. sativa has a time and dose-dependent inhibitory effect on the proliferation of MCF7 and AGS cancer cells. The vitality rates of MCF7 and AGS cells treated with N. sativa were 77.04-67.50% at 24 h, 65.28-39.14% at 48 h, and 48.95-32.31% at 72 h. The doses of 100 and 200 µg/mL were shown to be the most effective on both cancer cells. RT-PCR analysis revealed that N. sativa oil extract increased caspase-3 levels in both cell lines at higher concentrations and suppressed BCL2/Bax levels. Exposure of MCF7 and AGS cell lines to N. sativa caused a significant decrease in the expression of MMP2-9 and HSP60-70 genes over time, particularly at a dosage of 200 µg/mL compared to the control group (p < 0.05). CONCLUSIONS: Our findings indicate that N. sativa oil has a dose-dependent effect on cytotoxicity and the expression of apoptotic, heat shock proteins, and matrix metalloproteinases genes in breast and gastric cancer.

Selenium reduces acrylamide-induced testicular toxicity in rats by regulating HSD17B1, StAR, and CYP17A1 expression, oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.

This study investigated the effects of Selenium (Se) on testis toxicity induced by Acrylamide (ACR) in rats. In our study, 50 male adult rats were used, and the rats were divided into five groups; control, ACR, Se0.5 + ACR, Se1 + ACR, and Se1. Se and ACR treatments were applied for 10 days. On the 11th day of the experimental study, intracardiac blood samples from the rats were taken under anesthesia and euthanized. Sperm motility and morphology were evaluated. Dihydrotestosterone, FSH, and LH levels in sera were analyzed with commercial ELISA kits. MDA, GSH, TNF-α, IL-6, and IL-1ß levels and SOD, GPx, and CAT, activities were measured to detect the level of oxidative stress and inflammation in rat testis tissues. Expression analysis of HSD17B1, StAR, CYP17A1, MAPk14, and P-53 as target mRNA levels were performed with Real Time-PCR System technology for each cDNA sample synthesized from rat testis RNA. Testicular tissues were evaluated by histopathological, immunohistochemical, and immunofluorescent examinations. Serum dihydrotestosterone and FSH levels decreased significantly in the ACR group compared to the control group, while LH levels increased and a high dose of Se prevented these changes caused by ACR. A high dose of Se prevented these changes caused by ACR. ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.

Gossypin mitigates oxidative damage by downregulating the molecular signaling pathway in oleic acid-induced acute lung injury.

One of the leading causes of acute lung injury, which is linked to a high death rate, is pulmonary fat embolism. Increases in proinflammatory cytokines and the production of free radicals are related to the pathophysiology of acute lung injury. Antioxidants that scavenge free radicals play a protective role against acute lung injury. Gossypin has been proven to have antioxidant, antimicrobial, and anti-inflammatory properties. In this study, we compared the role of Gossypin with the therapeutically used drug Dexamethasone in the acute lung injury model caused by oleic acid in rats. Thirty rats were divided into five groups; Sham, Oleic acid model, Oleic acid+Dexamethasone (0.1 mg/kg), Oleic acid+Gossypin (10 and 20 mg/kg). Two hours after pretreatment with Dexamethasone or Gossypin, the acute lung injury model was created by injecting 1 g/kg oleic acid into the femoral vein. Three hours following the oleic acid injection, rats were decapitated. Lung tissues were extracted for histological, immunohistochemical, biochemical, PCR, and SEM imaging assessment. The oleic acid injection caused an increase in lipid peroxidation and catalase activity, pathological changes in lung tissue, decreased superoxide dismutase activity, and glutathione level, and increased TNF-α, IL-1ß, IL-6, and IL-8 expression. However, these changes were attenuated after treatment with Gossypin and Dexamethasone. By reducing the expression of proinflammatory cytokines and attenuating oxidative stress, Gossypin pretreatment provides a new target that is equally effective as dexamethasone in the treatment of oleic acid-induced acute lung injury.

Fisetin Attenuates Paracetamol-Induced Hepatotoxicity by Regulating CYP2E1 Enzyme.

Paracetamol is one of the drugs that cause hepatic damage. Fisetin has wide pharmacological effects such as anticancer, antiinflammatory and antioxidant. We aimed to evaluate the possible protective effect of fisetin on paracetamol-induced hepatotoxicity. Fisetin was administered at 25 and 50 mg/kg doses. Paracetamol was administered orally at a dose of 2 g/kg for induce hepatotoxicity 1 h after the fisetin and NAC treatments. The rats were sacrificed 24h after the Paracetamol administration. Tumor necrosis factor-alpha (TNF-α), NFκB and CYP2E1 mRNA levels and Superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) levels of livers were determined. Serum ALT, AST and ALP levels were measured. Histopathological examinations were also performed. Fisetin administration significantly decreased the ALT, AST and ALP levels in a dose dependent manner. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the treatment of fisetin. The TNF-α, NFκB and CYP2E1 gene expressions were significantly lower in both doses of the fisetin groups compared with the PARA group. Histopathological examinations showed that fisetin has hepatoprotective effects. This study showed that fisetin has the liver protective effects by increasing GSH, decreasing inflammatory mediators and CYP2E1.

Unlocking Synergistic Potential: Agomelatine Enhances the Chemotherapeutic Effect of Paclitaxel in Breast Cancer Cell Through MT1 Melatonin Receptors and ER-alpha Axis.

This study investigates the potential of agomelatine (AGO), a synthetic melatoninergic drug, in combination with paclitaxel (PTX) for the treatment of breast cancer. The effects of AGO, PTX and melatonin (MTN) on breast cancer cell viability were investigated, focusing on the role of MT1 receptors. Cell viability and gene expression were analyzed in MCF-7 and MDA-MB-231 breast cancer cell experiments. The results show that AGO has cytotoxic effects on breast cancer cells similar to MTN. Combining AGO and MTN with PTX showed synergistic effects in MCF-7 cells. The study also reveals differences in the molecular mechanisms of breast cancer between estrogen-positive MCF-7 cells and estrogen-negative MDA-MB-231 cells. Combination with AGO and PTX affects apoptosis-associated proteins in both cell types. The findings suggest that AGO, combined with PTX, may be a promising adjuvant therapy for breast cancer and highlight the importance of MTN receptors in its mechanism of action.

Antipsychotics Induced Reproductive Toxicity by Stimulating Oxidative Stress: A Comparative in Vivo and in Silico Study.

The pathophysiological mechanism behind the link between antipsychotic drugs and sexual dysfunction is still unknown. The goal of this research is to compare the potential effects of antipsychotics on the male reproductive system. Fifty rats were randomly assigned into the five groups indicated: Control, Haloperidol, Risperidone, Quetiapine and Aripiprazole. Sperm parameters were significantly impaired in all antipsychotics-treated groups. Haloperidol and Risperidone significantly decreased the level of testosterone. All antipsychotics had significantly reduced inhibin B level. A significant reduction was observed in SOD activity in all antipsychotics-treated groups. While GSH levels diminished, MDA levels were rising in the Haloperidol and Risperidone groups. Also, the GSH level was significantly elevated in the Quetiapine and Aripiprazole groups. By causing oxidative stress and altering hormone levels, Haloperidol and Risperidone are damaging to male reproductivity. This study represents useful starting point for exploring further aspects of the underlying mechanisms reproductive toxicity of antipsychotics.

Effects of naringin on oxidative stress, inflammation, some reproductive parameters, and apoptosis in acrylamide-induced testis toxicity in rat.

Acrylamide (ACR) is used in many fields such as cosmetics, paper, and textile industries. It also occurs at very high temperatures in some foods. Gonadotoxic effects of ACR have been found in experimental animals. Many studies use flavonoids to prevent the reproductive side effects of ACR. Naringin (NA) is a flavonoid and it has been determined by studies that it has no toxic effect on tissues. In our study, we aimed to determine the protective effect of NA against the damage of ACR on testicular tissue and the reproductive system in rats. In our study, 50 Spraque Dawley male rats weighing 220-250 grams were used. Control: Only intragastric saline was administered for 10 days. ACR: Animals received ACR (40 mg/kg, intraperitoneally) for 10 days. NA50+ACR: Animals were given NA for 10 days and each NA was one hour after the administration of ACR. NA100+ACR: Animals received NA for 10 days and one hour after each NA was given ACR. NA100: Animals were given NA for 10 days. At the end of the applications, the rats were euthanized by cervical dislocation under anesthesia. Serum FSH, LH, and Dihydrotestosterone levels were compared between the groups. In addition, oxidative stress, inflammation, expression of some reproductive enzymes, and apoptosis markers were determined in testicular tissues. When these parameters were compared between groups, ACR induced testicular dysfunction and tissue damage in rats. We determined that only the NA application did not cause tissue damage. and the administration of NA along with ACR significantly reduced ACR-induced testis toxicity.

Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of inflammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the effects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. METHODS: Adult male rats were divided into five groups: the CN (healthy rats, n = 6), OA (oleic acid administration, n = 6), OA + TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n = 6), OA + TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n = 6), and OA + DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n = 6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. RESULTS: Expressions of TNF-α, IL-1ß, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P < 0.05). The MDA level in lung tissues was statistically lower in the OA + TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P < 0.05). Histopathological findings such as thickening of the alveoli, hyperemia, and peribronchial cell infiltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA + TCZ-2, and OA + TCZ-4 groups. CONCLUSIONS: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were effective in preventing cytokine storms by downregulating the expression of proinflammatory cytokines including TNF-α, IL-1ß, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective effects against cell damage.

Evaluation of the protective effects of gossypin for ischemia/reperfusion injury in ovary tissue.

AIM: Ovarian ischemia-reperfusion (I/R) injury is a serious gynecological condition that affects women of reproductive age and reduces ovarian reserve. Management of I/R injury with detorsion causes reperfusion damage, in which oxidative stress plays a central role. This study aimed to investigate whether the gossypin (GOS) with antioxidant properties, a flavonoid, has beneficial effects on the biochemical, molecular, and histopathological aspects of ovarian I/R injury. METHODS: Thirty-three female Balb/c mice were randomly divided into five groups as follows: Healthy (Sham-operated control group), I/R (IR group), I/R + GOS 5 (I/R with GOS 5 mg/kg), I/R + GOS 10 (I/R with GOS 10 mg/kg), and I/R + GOS 20 (I/R with GOS 20 mg/kg). This was followed by 3 h of ischemia and subsequent reperfusion for 3 h after detorsion was exposed. GOS was injected 2 h before reperfusion. RESULTS: IL-1ß, IL-6, TNF-α, NF-κB, and CASP-3 mRNA expressions, SOD (superoxide dismutase) activity, GSH (glutathione), and MDA (malondialdehyde) levels, and histopathological changes were evaluated in ovarian tissue. Histological examination indicated that treatment of ovarian I/R injury with GOS led to the improvement of ovarian tissue, which was accompanied by an increase in SOD activity and GSH level and a decrease in MDA level, NF-κB, TNF-α, IL-1ß, and IL-6 expressions. GOS was also corrected by reducing the elevated expression of CASP-3 as apoptosis-change marker. CONCLUSION: These findings indicate that the treatment of GOS may be useful as a conservative approach to reverse I/R injury via amelioration of oxidative stress parameters and histopathological scores, attenuation of inflammation, and the suppression of apoptosis.

Biochemical Research of the Effects of Essential Oil Obtained from the Fruit of Myrtus communis L. on Cell Damage Associated with Lipopolysaccharide-Induced Endotoxemia in a Human Umbilical Cord Vein Endothelial Cells.

The aim of this study to investigate the potential effects of essential oils and compounds obtained from MC fruit on sepsis induced endothelial cell damage in human umbilical cord vein endothelial cells (HUVECs) at molecular and cellular levels on in vitro sepsis model. A sepsis model was induced by the application of LPS. The HUVEC treatment groups were as follows: control, LPS, MC, MC plus LPS, 1.8 cineole, 1.8 cineole plus LPS, α-pinene, α-pinene plus LPS, α-terpineol, and α-terpineol plus LPS. Following the treatments, cell proliferation was analyzed using the xCELLigence® system. The mRNA expression of various cytokines [tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and IL-6] and endothelial nitric oxide (eNOS) were determined by quantitative polymerase chain reaction (qPCR) analysis. The 1.8 cineole and α-pinene treatments at specific doses showed toxic effects on α-terpineine, although it did not result in a change in the cellular index as compared with that of the control group. The application of LPS to HUVECs led to a significant decrease in the cellular index, depending on the treatment time. It did not correct the decreased cell index of MC plus LPS and α-terpineol plus LPS groups as compared with that of the LPS-only group. The 1.8 cineole plus LPS treatment and α-pinene plus LPS treatment significantly increased the cell index as compared with that of the LPS-only treatment, and the cell index in these groups was closer to that of the control. According to the results of the qPCR analysis, neither the MC-only treatment nor the α-terpineol-only treatment significantly reduced cellular damage caused by LPS-induced increases in TNF-α, IL-1ß, IL-6, and eNOS mRNA expression. However, both the 1.8 cineole treatment and α-pinene treatments significantly decreased TNF-α, IL-1ß, IL-6, and eNOS mRNA expression induced by LPS. Volatile oil obtained from MC fruit and the MC compound α-terpineol had no effect on the decreased cell index and increased cytokine response due to LPS-induced endothelial cell damage. However, 1.8 cineole and α-pinene, other major components of MC fruit, ameliorated LPS-induced damage in HUVECs at cellular and biomolecular levels (TNF-α, IL-1ß, IL-6, and eNOS).

LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide) exerts anti-ulcer effects via 5-hydroxytryptamine receptor 7 activation on indomethacin-induced gastric ulcers in rats.

AIM: This study aimed to demonstrate the role of serotonin 7 receptor (5-HT7) and the effects of 5-HT7 agonists and antagonists in an indomethacin-induced gastric ulcer. MATERIAL AND METHOD: Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT7 agonist) and SB269970 (5-HT7 antagonist) were administered at 10 mg/kg as a pre-treatment. One hour after the drug treatments, 25 mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized. RESULTS: We analyzed the iNOS, eNOS, and 5-HT7 receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT7 mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT7 mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT7 agonist on gastric tissue. CONCLUSION: The study suggested that activation of 5-HT7 receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.

Dose-dependent effect of radiation on resorbable blast material titanium implants: an experimental study in rabbits.

BACKGROUND: Radiotherapy is a commonly used treatment modality in head and neck cancer; however, it also negatively affects healthy structures. Direct damage to oral soft and hard tissue frequently occurs with radiotherapy. In this study, we aimed to evaluate the effect of radiotherapy on bone surrounding titanium dental implants via biomechanical and molecular methods. MATERIALS AND METHODS: Fifty-four implants were inserted in the left tibiae of 18 adult male New Zealand rabbits (3 implants in each rabbit). After 4 weeks of the implant surgery, the left tibiae of 12 rabbits were subjected to a single dose of irradiation (15 Gy or 30 Gy). Four weeks after the irradiation, rabbits were sacrificed and removal torque test was done for the biomechanical evaluation. Bone morphogenetic protein-2 (Bmp-2) and fibroblast growth factor-2 (Fgf-2) expression analyses were performed with Real-time PCR. Statistical analysis was done using SPSS. RESULTS: The control group showed significantly higher removal torque value than the 15 and 30 Gy irradiation groups, and the 15 Gy irradiation group had higher removal torque value than the 30 Gy irradiation group (p < .001). The 15 Gy and 30 Gy irradiation groups had significantly lower Bmp-2 and Fgf-2 mRNA expressions than the control group (p < .001). In addition, the 30 Gy irradiation group had significantly lower Bmp-2 (p < .01) and Fgf-2 mRNA expressions (p < .001) than the 15 Gy group. CONCLUSION: Radiotherapy with 15 and 30 Gy doses can adversely affect osseointegration of implants by reducing the quality of bone and impairing the bone-to-implant contact. The mechanism of action seems to be related to alterations in Bmp-2 and Fgf-2 mRNA expressions.

A new update for radiocontrast-induced nephropathy aggravated with glycerol in rats: the protective potential of epigallocatechin-3-gallate.

Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.

Mitigation of Acute Hepatotoxicity Induced by Cadmium Through Morin: Modulation of Oxidative and Pro-apoptotic Endoplasmic Reticulum Stress and Inflammatory Responses in Rats.

Cadmium (Cd) is a toxic heavy metal with significant environmental health hazards. It enters the body through various routes with tissue accumulation. The relatively longer half-life with slow body clearance significantly results in hepatotoxicity during its liver detoxification. Therefore, researchers are exploring the potential use of herbal-derived phytocomponents to mitigate their toxicity. Here, we investigated, for the first time, the possible ameliorative effect of the phytochemical Morin (3,5,7,29,49-pentahydroxyflavone) against acute Cd-induced hepatotoxicity while resolving its underlying cellular mechanisms in a rat animal model. The study involved 50 adult male Sprague-Dawley rats weighing 200-250 g. The animals were divided into five equal groups: control, Cd, Morin100 + Cd, Morin200 + Cd, and Morin200. The 2nd, 3rd, and 4th groups were intraperitoneally treated with Cd (6.5 mg/kg), while the 3rd, 4th, and 5th groups were orally treated with Morin (100 and 200 mg/kg) for 5 consecutive days. On the 6th day, hepatic function (serum ALT, AST, ALP, LDH enzyme activities, and total bilirubin level) testing, transcriptome analysis, and immunohistochemistry were performed to elucidate the ameliorative effect of Morin on hepatotoxicity. In addition to restoring liver function and tissue injury, Morin alleviated Cd-induced hepatic oxidative/endoplasmic reticulum stress in a dose-dependent manner, as revealed by upregulating the expression of antioxidants (SOD, GSH, Gpx, CAT, and Nrf2) and decreasing the expression of ER stress markers. The expression of the proinflammatory mediators (TNF-α, IL-1-ß, and IL-6) was also downregulated while improving the anti-inflammatory (IL-10 and IL-4) expression levels. Morin further slowed the apoptotic cascades by deregulating the expression of pro-apoptotic Bax and Caspase 12 markers concomitant with an increase in anti-apoptotic Blc2 mRNA expression. Furthermore, Morin restored Cd-induced tissue damage and markedly suppressed the cytoplasmic expression of JNK and p-PERK immunostained proteins. This study demonstrated the dose-dependent antioxidant hepatoprotective effect of Morin against acute hepatic Cd intoxication. This effect is likely linked with the modulation of upstream p-GRP78/PERK/ATF6 pro-apoptotic oxidative/ER stress and the downstream JNK/BAX/caspase 12 apoptotic signaling pathways.

The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats.

Objectives: Cadmium (CD) causes widespread and severe toxic effects on various tissues. Studies have shown that apoptosis, inflammation, and endoplasmic reticulum stress play a role in organ damage caused by CD. Phenolic compounds with strong antioxidant effects are found in various fruits and vegetables. One of these compounds is Gallic acid (GA), which is found both free and hydrolyzable in grapes, pomegranate, tea, hops, and oak bark. Result of various studies show that GA has active antioxidant, anti-inflammatory, and anti-apoptotic properties. In our study, we investigated the mechanism of the protective effect of GA on CD-induced hepatotoxicity in rats. Materials and Methods: In this study, 50 adult male Sprague Dawley rats weighing approximately 200-250 g were used and the rats were divided into 5 groups: Control, CD, GA50+CD, GA100+CD, and GA100. The rats were treated with GA (50 and 100 mg/kg body weight), and Cd (6.5 mg/kg) was administrated to the rats for 5 consecutive days. The liver enzymes, TB levels in serum samples, oxidative stress, inflammation, ER stresses, apoptosis marker, histopathology, 8-OHDG, and caspase-3 positivity were analyzed. Results: CD administration significantly increased liver enzyme levels (AST, ALT, ALP, and LDH), MDA, IL-1-ß, IFN-γ, TNF-α, IL-10, IL-6, GRP78, CHOP, ATF6, p -IRE1, sXBP, Bax mRNA expression, Caspase 3, and 8-OHdG expression (P<0.05). These values were found to be significantly lower in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). CD administration significantly decreased the expression levels of TB, IL-4, SOD, GSH, CAT, GPX, and Bcl-2 mRNA (P<0.05). These values were found to be significantly higher in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). Conclusion: The results of the present study indicated that GA prevented Cd-induced hepatic oxidative stress, inflammation, ER stress, apoptosis, and tissue damage in rats.

Management of Adult Chiari I Patients Based on CSF Flow Magnetic Resonance Imaging: Experience of Two Neurosurgical Centers.

BACKGROUND AND STUDY AIMS: Chiari malformation type 1 (CM1) is one of the most discussed neurosurgical disorders. No consensus exists how to manage adult CM1 patients. We aimed to evaluate all adult CM1 patients consecutively managed at our institutions and discuss our approach based on the phase-contrast (PC) magnetic resonance imaging (MRI). PATIENTS AND METHODS: The medical charts of adult patients diagnosed with CM1 at two referral neurosurgical centers between 2010 and 2017 were reviewed. The patients were either managed conservatively or surgically. We evaluated the patients clinically with the Chicago Chiari Outcome Scale (CCOS). The radiologic diagnosis was based on both craniocervical and PC-MRI. RESULTS: Ninety adult CM1 patients were managed conservatively. Conservative treatment failed in 5 of these 90 patients. Seventy-two patients (including those 5 patients who did not benefit from conservative treatment) underwent posterior fossa decompression with duraplasty. Eighty-five patients (94.4%) from the conservative group and 61 patients (84.7%) from the surgical group were treated successfully. An aqueductal stroke volume (ASV) value of 12 µL was found as the cutoff value for surgical candidates. A strong positive correlation between the increase in ASV values and clinical improvement was observed. CONCLUSIONS: PC-MRI can help in the management and follow-up of adult CM1 patients. Conservative management is possible in selected symptomatic CM1 patients with a high ASV (ASV > 15 µL). Surgery should be considered in patients with an ASV ≤ 12 µL. CM1 patients with ASV ≤12 to >15 µL require close follow-up. Long-standing symptoms, severe sleep apnea, symptoms influencing functionality, and syrinx are factors that affected outcomes negatively.

Surgical Outcome of Spinal Subdural Abscesses: A Report of Four Consecutive Patients and Brief Review of the Literature.

BACKGROUND AND STUDY AIMS: Spinal subdural abscesses (SSAs) are rare and have a poor prognosis, especially when they are diagnosed late. In the literature, most cases of SSAs have been reported as case reports and small case series. In this study, we aimed to evaluate the surgical outcomes of four consecutive SSA patients. MATERIAL AND METHODS: In this retrospective study, we reviewed the medical charts of four SSA patients who underwent surgical intervention at two neurosurgical centers from September 2012 to September 2019. RESULTS: Our series comprised four patients (three females and one male) with SSA (intradural-extramedullary) who were treated surgically. Holocord SSA was observed in two patients. The mean age was 15.1 ± 17.1 years. Unsteady gait and weakness of legs was the presenting symptom in all patients. The mean preoperative course was 5.3 ± 3.4 weeks. The causative pathogens were methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Mycobacterium tuberculosis. In the fourth case, the pathogen was non-M. tuberculosis. In the 44th postoperative month, the patient underwent surgery for an intramedullary abscess. The causative pathogen was E. coli. Except for one adolescent male who was paraplegic at presentation, improvement was observed in all patients at their last follow-up after 54.0 ± 35.9 months after surgery. CONCLUSION: Early diagnosis and urgent surgical intervention are essential for a good prognosis in SSA cases. We recommend drainage followed by appropriate antibiotics.

Oxidative Stress Level in Patients with Subarachnoid Hemorrhage.

BACKGROUND: One of the antioxidant mechanisms is the dynamic balance between thiol and disulfide, which, in subarachnoid hemorrhage and other chronic diseases, is disrupted in favor of the latter. The two most commonly used oxidative stress (OS) biochemical markers are the oxidative stress index (OSI) value, which indicates the total oxidant status (TOS) and total antioxidant status (TAS) balance, and the thiol-disulfide (TDS) value, which indicates the total thiol (TT) and native thiol (NT) balance. High OS levels require further investigations. We aimed to investigate the OS level in aneurysmal SAH (aSAH) patients. METHODS: In this clinical prospective study, blood samples were collected from 50 consecutively treated patients with aSAH and 50 volunteers. Serum TOS, TAS, TT, and NT levels were measured using Erel's method via a spectrophotometer. The Glasgow Coma Scale (GCS) scores, Fisher grades, length of hospital stay (LOS), and the Glasgow Outcome Scale (GOS) scores were recorded. Consequently, the OSI and TDS values were calculated in all participants. RESULTS: A statistically significant difference was observed in the TAS, TOS, OSI, and TDS values between the aSAH patients and the controls. The TT and NT values were significantly lower in aSAH patients than in the controls. A correlation was identified between the OSI values and the GCS scores. Although a correlation was observed between the TDS values and the LOS, no correlation was found between the OSI and the TDS values. CONCLUSION: The OSI and TDS, which are OS indicators, might serve as the additional objective nominal data to evaluate the treatment efficacy and follow-up for SAH patients. Moreover, decreasing the OSI values and increasing the TT values can be used as improvement indicators in the treated aSAH patients. If we can reduce the OS at the early stage of SAH, it could improve the prognosis by reducing both the morbidity and mortality rates. Further randomized investigations are required to prove the findings in this prospective study.

Effects of Methylprednisolone in the Treatment of Spinal Cord Injuries by Evaluation of microRNA-21: An Experimental Study.

BACKGROUND AND STUDY AIMS: Spinal cord injury (SCI) is one of the most complicated pathologies that affect active young males. miR-21 primarily regulates several cellular processes. We aimed to elucidate the regulatory role of miR-21 and test methylprednisolone as a disease-modifying agent on experimental SCI tissues. METHODS: A total of 36 8- to 10-week-old adult female Sprague-Dawley rats weighing 250 to 300 g were used. Animals were randomly divided into six groups. Except for groups 1 and 4, the spinal trauma model was applied to all animal groups using the clipping method. In groups 3 and 6, methylprednisolone was given. For real-time polymerase chain reaction (PCR) investigations, rats in groups 1, 2, and 3 were reoperated on after the first postoperative day, whereas those in groups 4, 5, and 6 were reoperated on after postoperative day 7 and spinal cord samples from the laminectomy area were removed for gene expression analysis. Relative gene expression of miR-21, Gfap, Vim, Stat3, Faslg, Pten, Bax, Bcl2, Cox2, and Il6 were determined with quantitative reverse transcription (qRT) PCR. RESULTS: In group 3, the miR-21 expression significantly increased compared with groups 1 and 2. When compared with group 3, a decrease in miR-21 expression was observed in group 6 (p < 0.05). When compared with group 4, group 6 had lower levels of Gfap, Pten, Stat3, and Bax (p < 0.05). CONCLUSIONS: miR-21 supports the beneficial aspects of the body's healing mechanisms following SCI. In the acute phase, the use of methylprednisolone increases miR-21 expression in the early period of trauma. Methylprednisolone increases some astrogliosis and inflammation biomarkers' levels; however, it did not affect the apoptotic biomarkers.

Effects of simultaneous versus post exposure epigallocatechin-3-gallate treatment on aluminum induced neurotoxicity in rat hippocampus: A multi-approach study.

Chronic aluminium(Al) exposure can affect the antioxidant and glutaminergic systems through N-methyl-D-aspartate receptors (NMDAR). This study was aimed to investigate the neurotoxic effect of Al through different mechanisms in rat hippocampus and to evaluate the protective role of epigallocatechin gallate (EGCG), a well-known antioxidant, with simultaneous administration of Al,as well as post-treatment after Al exposure.For this purpose, aluminum chloride(AlCl3) was administered simultaneously with two different EGCG doses for 8 weeks as the first part of the study.In the second part of the study, after 4 weeks of AlCl3 pre-administration, two different EGCG doses were also administered during four additional weeks as post-treatment.Al administration led to oxidative stress and increased acetylcholinesterase levels.NMDAR subunit mRNA expressions were down-regulated by Al, which was apparent in NMDAR1/2B subunits.Simultaneous EGCG treatment has shown a better neuroprotective effect in terms of these mechanisms and represents novel approach for the prevention of neurodegenerative diseases likely to be induced by Al.