Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.

Chemotherapy and radiotherapy are widely used in clinical practice across the globe as cancer treatments. Intrinsic or acquired chemoresistance poses a significant problem for medical practitioners and researchers, causing tumor recurrence and metastasis. The most dangerous kind of malignant brain tumor is called glioblastoma multiforme (GBM) that often recurs following surgery. The most often used medication for treating GBM is temozolomide chemotherapy; however, most patients eventually become resistant. Researchers are studying preclinical models that accurately reflect human disease and can be used to speed up drug development to overcome chemoresistance in GBM. Non-coding RNAs (ncRNAs) have been shown to be substantial in regulating tumor development and facilitating treatment resistance in several cancers, such as GBM. In this work, we mentioned the mechanisms of how different ncRNAs (microRNAs, long non-coding RNAs, circular RNAs) can regulate temozolomide chemosensitivity in GBM. We also address the role of these ncRNAs encapsulated inside secreted exosomes.

Cognitive Dysfunction and Exercise: From Epigenetic to Genetic Molecular Mechanisms.

Maintaining good health is crucial, and exercise plays a vital role in achieving this goal. It offers a range of positive benefits for cognitive function, regardless of age. However, as our population ages and life expectancy increases, cognitive impairment has become a prevalent issue, often coexisting with age-related neurodegenerative conditions. This can result in devastating consequences such as memory loss, difficulty speaking, and confusion, greatly hindering one's ability to lead an ordinary life. In addition, the decrease in mental capacity has a significant effect on an individual's physical and emotional well-being, greatly reducing their overall level of contentment and causing a significant financial burden for communities. While most current approaches aim to slow the decline of cognition, exercise offers a non-pharmacological, safe, and accessible solution. Its effects on cognition are intricate and involve changes in the brain's neural plasticity, mitochondrial stability, and energy metabolism. Moreover, exercise triggers the release of cytokines, playing a significant role in the body-brain connection and its impact on cognition. Additionally, exercise can influence gene expression through epigenetic mechanisms, leading to lasting improvements in brain function and behavior. Herein, we summarized various genetic and epigenetic mechanisms that can be modulated by exercise in cognitive dysfunction.

Exosomes released from U87 glioma cells treated with curcumin and/or temozolomide produce apoptosis in naive U87 cells.

Glioblastoma (GBM) remains the most lethal brain tumor without any curative treatment. Exosomes can mediate cell-to-cell communication, and may function as a new type of targeted therapy. In this study, the therapeutic benefits of exosomes generated by U87 cells treated with curcumin and/or temozolomide were investigated. The cells were cultured and treated with temozolomide (TMZ), curcumin (Cur), or their combination (TMZ+Cur). Exosomes were isolated with a centrifugation kit and characterized using DLS, SEM, TEM, and Western blotting. The levels of exosomal BDNF and TNF-α were measured. Naïve U87 cells were treated with the isolated exosomes, and the effects on apoptosis-related proteins HSP27, HSP70, HSP90, and P53 were assessed. All exosomes, Cur-Exo, TMZ-Exo, and TMZ+Cur-Exo increased cleaved caspase 3, Bax, and P53 proteins, while reducing HSP27, HSP70, HSP90, and Bcl2 proteins. Moreover all treatment groups increased apoptosis in naïve U87 recipient cells. Exosomes released from treated U87 cells had less BDNF and more TNF-α compared to exosomes released from naive U87 cells. In conclusion, we showed for the first time that exosomes released from drug-treated U87 cells could be a new therapeutic approach in glioblastoma, and could reduce the side effects produced by drugs alone. This concept needs to be further examined in animal models before clinical trials could be considered.

Effect of tramadol on apoptosis and synaptogenesis in hippocampal neurons: The possible role of µ-opioid receptor.

Tramadol is a synthetic opioid with centrally acting analgesic activity that alleviates moderate to severe pain and treats withdrawal symptoms of the other opioids. Like other opioid drugs, tramadol abuse has adverse effects on central nervous system components. Chronic administration of tramadol induces maladaptive plasticity in brain structures responsible for cognitive function, such as the hippocampus. However, the mechanisms by which tramadol induces these alternations are not entirely understood. Here, we examine the effect of tramadol on apoptosis and synaptogenesis of hippocampal neuronal in vitro. First, the primary culture of hippocampal neurons from neonatal rats was established, and the purity of the neuronal cells was verified by immunofluorescent staining. To evaluate the effect of tramadol on neuronal cell viability MTT assay was carried out. The western blot analysis technique was performed for the assessment of apoptosis and synaptogenesis markers. Results show that chronic exposure to tramadol reduces cell viability of neuronal cells and naloxone reverses this effect. Also, the level of caspase-3 significantly increased in tramadol-exposed hippocampal neurons. Moreover, tramadol downregulates protein levels of synaptophysin and stathmin as synaptogenesis markers. Interestingly, the effects of tramadol were abrogated by naloxone treatment. These findings suggest that tramadol can induce neurotoxicity in hippocampal neuronal cells, and this effect was partly mediated through opioid receptors.

ß2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression.

Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma. Gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) is a new strategy for GBM treatment. As the connexin 43 (Cx43) levels are downregulated in GBM cells, it seems that the upregulation of Cx43 could improve the efficacy of the gene therapy. This study aims to evaluate the effect of clenbuterol hydrochloride (Cln) as a ß2-adrenergic receptor agonist on HSV-TK/GCV gene therapy efficacy in human GBM cells using olfactory ensheathing cells (OECs) as vectors. The lentivirus containing the thymidine kinase gene was transduced to OECs and the effective dose of GCV on cells was measured by MTT assay. We found that Cln upregulated Cx43 expression in human GBM cells and OECs and promoted the cytotoxic effect of GCV on the co-culture cells. Western blot results showed that Cln increased the cleaved caspase-3 expression and the Bax/Bcl2 ratio in the co-culture of GBM cells and OEC-TK. Also, the flow cytometry results revealed that Cln increased apoptosis in the co-culture of GBM cells and OEC-TK cells. This study showed that Cln via upregulation of Cx43 expression could enhance the bystander effect of HSVTK-GCV gene therapy in human GBM cells.

Microfluidics for detection of exosomes and microRNAs in cancer: State of the art.

Exosomes are small extracellular vesicles with sizes ranging from 30-150 nanometers that contain proteins, lipids, mRNAs, microRNAs, and double-stranded DNA derived from the cells of origin. Exosomes can be taken up by target cells, acting as a means of cell-to-cell communication. The discovery of these vesicles in body fluids and their participation in cell communication has led to major breakthroughs in diagnosis, prognosis, and treatment of several conditions (e.g., cancer). However, conventional isolation and evaluation of exosomes and their microRNA content suffers from high cost, lengthy processes, difficult standardization, low purity, and poor yield. The emergence of microfluidics devices with increased efficiency in sieving, trapping, and immunological separation of small volumes could provide improved detection and monitoring of exosomes involved in cancer. Microfluidics techniques hold promise for advances in development of diagnostic and prognostic devices. This review covers ongoing research on microfluidics devices for detection of microRNAs and exosomes as biomarkers and their translation to point-of-care and clinical applications.

Non-coding RNAs and glioblastoma: Insight into their roles in metastasis.

Glioma, also known as glioblastoma multiforme (GBM), is the most prevalent and most lethal primary brain tumor in adults. Gliomas are highly invasive tumors with the highest death rate among all primary brain malignancies. Metastasis occurs as the tumor cells spread from the site of origin to another site in the brain. Metastasis is a multifactorial process, which depends on alterations in metabolism, genetic mutations, and the cancer microenvironment. During recent years, the scientific study of non-coding RNAs (ncRNAs) has led to new insight into the molecular mechanisms involved in glioma. Many studies have reported that ncRNAs play major roles in many biological procedures connected with the development and progression of glioma. Long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are all types of ncRNAs, which are commonly dysregulated in GBM. Dysregulation of ncRNAs can facilitate the invasion and metastasis of glioma. The present review highlights some ncRNAs that have been associated with metastasis in GBM. miRNAs, circRNAs, and lncRNAs are discussed in detail with respect to their relevant signaling pathways involved in metastasis.

Therapeutic potentials of curcumin in the treatment of glioblstoma.

Glioblastoma multiforme (GBM), a greatly aggressive malignancy of the brain, is correlated with a poor prognosis and low rate of survival. Up to now, chemotherapy and radiation therapy after surgical approaches have been the treatments increasing the survival rates. The low efficacy of mentioned therapies as well as their side-effects has forced researchers to explore an appropriate alternative or complementary treatment for glioblastoma. In experimental models, it has been shown that curcumin has therapeutic potentials to fight against GBM. Given that curcumin has pharmacological effects against cancer stem cells, as major causes of resistance to therapy in glioblastoma cells. Moreover, it has been showed that curcumin exerts its therapeutic effects on GBM cells via affecting on apoptosis, oxidant system, and inflammatory pathways. Curcumin would possess a synergistic impact with chemotherapeutic agents. Herein, we summarized the current findings on curcumin as therapeutic agent in the treatment of GBM.

Anesthesia Related Complications of Gastrointestinal Endoscopies; A Retrospective Descriptive Study.

BACKGROUND Gastrointestinal endoscopic procedures are widely used for diagnostic and therapeutic measures. Analgesia and sedation/anesthesia are inseparable parts of these studies and their related complications are inevitable. METHODS In a retrograde descriptive study in Shahid Beheshti Hospital, affiliated to Qom University of Medical Sciences, Qom, Iran from March 2013 to March 2017, we gathered information regarding common anesthesia related complications and analyzed them. RESULTS 44659 procedures were performed during the study period and records of 21342 men (47.79%) and 23317 women (52.21%) were evaluated. Hemodynamic instability (9998; 22.39%), dysrhythmia (1600; 3.58%), desaturation (608; 1.36%), prolonged apnea (34; 0.08%), aspiration (43; 0.10%), postoperative nausea and vomiting (PONV) (636; 1.42%), headache (106; 0.24%), delirium (51; 0.11%), aphasia (1; 0.00%), masseter muscle spasm (1; 0.01%), myocardial infarction (2; 0.00%), and death (5; 0.01%) were seen in the patients. CONCLUSION Sedation/anesthesia is enough safe in gastrointestinal endoscopic procedures to enhance the patients' satisfaction and cooperation. If anesthesia with spontaneous breathing and unsecure airway is selected for this purpose, vigilance of anesthesia provider will be the key element of uneventful and safe procedure.

Job Satisfaction and Turnover Intention Among Anesthesiologists: An Iranian Study.

Job satisfaction is shown to be the strongest predictor of turnover intention and actual leaving among healthcare personnel. The aim of this study was to identify job satisfaction and turnover intention among anesthesiologists in Iran. This cross-sectional survey was conducted among 177 anesthesiologists. A set of self-administered questionnaires were applied to evaluate job satisfaction and intention to quit anesthesiology. It was found 39.5% of the participants reported that they wanted to quit the anesthesiology profession in the next year. Multivariate logistic regression analysis revealed that job satisfaction was a significant predictor of intention to leave after controlling for other independent variables. A significant association was found between job satisfaction and anesthesiologists' intention to leave their current employment. Therefore, increasing anesthesiologists' job satisfaction can lead to a higher propensity to retention in the healthcare system.

Dermatological manifestations in hemodialysis patients in Iran: A systematic review and meta-analysis.

BACKGROUND: Dermatologic complications are common in patients with end-stage renal disease and also have a high diversity. OBJECTIVES: This meta-analysis reviews prevalence of dermatological manifestations among hemodialysis patients in Iran. MATERIALS AND METHODS: Using PubMed and NLM Gateway (for MEDLINE), Institute of Scientific Information (ISI), and SCOPUS as the main international electronic data sources, and Iran-Medex, Irandoc, and Scientific Information Database, as the main domestic databases with systematic search capability, we systematically searched surveys, papers, and reports on the prevalence of dermatological manifestations (until February 2016). Heterogeneity of reported prevalence's between studies was assessed using the Q test; overall prevalence of dermatological manifestations was estimated using random-effect meta-analysis model. RESULTS: We found 1229 records; from them, a total of eight studies comprising 917 hemodialysis patients were included. In all of studies, skin discoloration, pruritus and xerosis have the highest prevalence. According to random-effect meta-analysis model, the pooled prevalence of skin discoloration, pruritus, ecchymosis, xerosis, and half-and-half nail in hemodialysis patients were 48.03% (95% CI: 45.09-51.01), 52.85% (95%CI: 49.23-56.47), 19.88 (95% CI: 17.57-22.19), 51.14% (95% CI: 48.25-54.02), and 18.50% (95% CI: 16.0-21.0), respectively. CONCLUSIONS: his study shows that the prevalence of dermatological manifestations seems high among the hemodialysis patients in Iran, and skin discoloration, pruritus, and xerosis are more common.

MicroRNAs and exosomes in depression: Potential diagnostic biomarkers.

Depression is known as one of important psychiatric disorders which could be associated with disability among various populations. Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV) and international statistical classification of diseases and related health problems (ICD-10) could be used as subjective diagnostic schemes for identification of mental disorders such as depression. Utilization of subjective diagnostic schemes are associated with limitations. Hence, it seems that employing of new diagnosis platforms is required. Multiple lines of evidence indicated that measurement of several biomarkers could be useful for detection patients with depression. Among of various types of biomarkers, microRNAs (miRNAs) have been emerged as powerful tools for diagnosis patients with depression. MiRNAs are small non-coding RNAs which act as epigenetic regulators. It has been showed that these molecules have critical roles in pathogenesis of many diseases such as depression. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in initiation and progression of depression. Hence, miRNAs could be used as diagnostic and therapeutic biomarkers in patients with depression. Besides miRNAs, exosomes as nano- carriers could have been emerged as diagnostic biomarkers in several diseases such as depression. These vesicles are able to carry several cargos such as DNAs, proteins, mRNAs, and miRNAs to recipient cells. Here, we summarized several miRNAs involved in pathogenesis and response to treatment of depression which could be used as diagnostic biomarkers. Moreover, we highlighted exosomes as new diagnostic biomarkers for patients with depression.

Teucrium polium L. Improves Blood Glucose and Lipids and Ameliorates Oxidative Stress in Heart and Aorta of Diabetic Rats.

BACKGROUND: Diabetes mellitus (DM) is a prime risk factor for cardiovascular disease. The convincing experimental and clinical evidence indicated that the onset of DM is closely associated with oxidative stress and that the generation of reactive oxygen species increases in both the types of diabetes. The aim of the present study was to evaluate the effect of Teucrium polium (TP) hydroalcoholic extract on the blood glucose, cholesterol, triglyceride, and oxidative stress markers of the heart and aorta in streptozotocin (STZ)-induced diabetic rats. METHODS: The male Wistar rats assigned into six groups (n = 8 in each group): Control, diabetic, and diabetic rats treated with TP extract (100, 200, and 400 mg/kg) or met and metformin (300 mg/kg) formin (300 mg/kg) group, by daily gavage for 6 weeks. Diabetes was induced by injection of STZ (60 mg/kg, i.p). Serum lipids and glucose, malondialdehyde (MDA) level, total thiol level, and also the activities of Cu, Zn-superoxide dismutase (SOD) in the cardiac and aortic tissues were assessed. RESULTS: TP extract reduced serum glucose, triglyceride and cholesterol. The MDA levels were reduced significantly in all TP-treated groups and metformin. Total thiol levels were improved in the heart and aorta of TP extract-treated groups and metformin compared to the diabetic rats. The activity of SOD in the cardiac and aortic tissues of TP extract- and metformin-treated groups was higher than diabetic group. CONCLUSIONS: The results showed that chronic administration of TP in STZ-induced diabetic rats could decrease blood glucose, cholesterol, and triglyceride and also attenuate the oxidative stress in the aortic and cardiac tissues.

Protective effect of hydroalcoholic extract of Teucrium polium on diabetes-induced testicular damage and serum testosterone concentration.

BACKGROUND: Diabetes has an adverse effect on spermatogenesis by rising oxidative stress. OBJECTIVE: The aim of this study was to investigate the effect of Teucrium Polium extract administration on spermatogenesis and testicular structure in diabetic rats induced with Streptozotocin. MATERIALS AND METHODS: 32 male Wistar rats were randomly divided into four groups (n=8/each): control group, diabetic group received distilled water, and two experimental groups included diabetic rats treated with 50 and 100 mg/body weigh of Teucrium Polium extract for 6 six weeks. After six weeks, the left testis had been removed and the morphometrical study was performed. Blood samples were collected from the ophthalmic veins of the rats and plasma levels of glucose and testosterone hormone were measured afterward. RESULTS: The reduction in diameters of the seminiferous tubules and thickening of the wall of the seminiferous tubules (p=0.05) were seen in diabetic rats. Also, the degenerative changes in cells arrangement have been observed. Statistical analysis showed the use of Teucrium Polium significantly improved the above disorders in treatment group (100 mg/BW) in contrast to the non treated diabetic group (p=0.05), but no significant difference was seen between the experimental group treated with 50 mg/BW of Teucrium polium and diabetic group (p=0.08). These data also revealed that treatment of diabetic rats with 100 mg/BW of Teucrium Polium extract significantly improves the change in serum glucose (p=0.001) and testosterone (p=0.03). CONCLUSION: The results of the present study indicate that diabetes produces degenerative changes in the testis of rats and administration of Teucrium polium reduces complications resulted from diabetes.

Kidney stone formation and antioxidant effects of Cynodon dactylon decoction in male Wistar rats.

OBJECTIVES: The antioxidant capacity impairs in kidney and urinary bladder of animals with stone disease. Herbal medicine can improve the antioxidant condition of renal tissue. Cynodon dactylon (C. dactylon) is a medicinal plant with antioxidative and diuretic properties and different preparations of this plant have shown promising effects in stone disease. Assessment of the whole plant decoction to prevent kidney stone disease as well as its antioxidant effects was the aim of this paper. MATERIALS AND METHODS: Fifty male Wistar rats were randomly divided into 5 experimental groups (n=10). One group was left without treatment and four groups received ethylene glycol (1% v/v) in drinking water for 6 weeks. Three doses of Cynodon dactylon aqueous decoction (12.5, 50 and 200 mg/kg BW) were added to the drinking water of groups 3-5. Finally, water intake, 24-hour urine volume, MDA, total thiol concentration and FRAP value were measured in the serum and kidney tissues. The CaOx depositions were evaluated by hematoxylin and eosin staining. RESULTS: Compared to the ethylene glycol-treated group, 200 mg/kg C. dactylon, lowered stone incidents, decreased urine volume, increased FRAP/g Cr (43%) and thiol content (p<0.05) with no significant alteration of water intake, MDA decreased significantly compared to C. dactylon 12.5 (p<0.01). Kidney weight increased and body weight decreased in ethylene glycol-treated group compared to the control group (p<0.05). CONCLUSION: A minimum dose of 200 mg/kg C. dactylon reduced stone formation and simultaneously increased total antioxidant power of serum and preserved MDA content and water.

Protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments in ovariectomized rats.

BACKGROUND: Regarding the anti-oxidative effects on the central nervous system, the possible protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments was investigated in ovariectomized (OVX) rats. MATERIALS AND METHODS: The OVX rats treated by (1) vehicle, (2) scopolamine, and (3-4) scopolamine plus estradiol (20 or 20 or 60 µg/kg). Estradiol was administered (20 or 60 µg/kg, intraperitoneally) daily for 6 weeks after ovariectomy. The rats were examined for learning and memory using passive avoidance test. Scopolamine (2 mg/kg) was injected 30 min after training in the test. The brains were then removed to determine malondialdehyde (MDA) and thiol contents. RESULTS: Scopolamine shortened the time latency to enter the dark compartment in (P < 0.01). Compared to scopolamine, pretreatment by both doses of estradiol prolonged the latency to enter the dark compartment (P < 0.01). The brain tissues MDA concentration as an index of lipid peroxidation was decreased (P < 0.05). Pretreatment by estradiol lowered the concentration of MDA, while it increased thiol content compared to scopolamine (P < 0.05 and P < 0.01). CONCLUSIONS: These results allow us to suggest a protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments in OVX rats.

Nigella sativa seed decreases endothelial dysfunction in streptozotocin-induced diabetic rat aorta.

OBJECTIVE: Diabetes is an important risk factor for cardiovascular events. The great percent of morbidity in patients with diabetes is due to endothelial dysfunction. The present study investigated the effects of hydroalcholic extract of Nigella sativa (N. sativa) on contractile and dilatation response of isolated aorta in streptozotocin (STZ)-induced diabetic rat. MATERIALS AND METHODS: Rats were divided into six experimental groups (control, untreated STZ-diabetic, and N. sativa hydroalcholic extract or metformin-treated diabetic rats). Treated rats received N. sativa extract (100, 200, and 400 mg/kg) or metformin (300 mg/kg) by gavage, daily for 6 weeks. Isolated rat thoracic rings were mounted in an organ bath system then contractile and dilatation responses induced by phenylephrine (PE), acetylcholine (ACh), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations. RESULTS: The lower concentrations of N. sativa seed extract (DE 100 and DE 200) and metformin significantly reduced the contractile responses to higher concentrations of PE (10(-6) - 10(-5) M) compared to diabetic group (p<0.05 to p<0.01). The relaxation response to Ach 10(-8) M, was increased in DE 200 and metformin groups compared to diabetic group (p<0.05). The relaxation responses to Ach 10(-7) - 10(-5) M were significantly higher in all treated groups compared to diabetic group (p<0.05 to p<0.001). CONCLUSION: Chronic administration of N. sativa seed extract has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats.

Neuronal nitric oxide synthase has a role in the detrimental effects of lipopolysaccharide on spatial memory and synaptic plasticity in rats.

BACKGROUND: The role of neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced memory and synaptic plasticity impairment was investigated. METHODS: The rats were divided and treated as follows: (1) control (saline), (2) LPS, (3) 7NI (7-nitroindazole as a nNOS inhibitor)-LPS and (4) 7NI. RESULTS: In a Morris water maze, the LPS group took a longer amount of time and traveled a greater distance to reach the platform, this was prevented by 7NI. Malondialdehyde (MDA) and nitric oxide (NO) metabolites in the hippocampus of the LPS group were higher while the total thiol, superoxide dismutase and catalase were lower than that of the controlled specimen. Pre-treatment using 7NI prevented the changes in the biochemical criteria. The slope and amplitude of the field excitatory post-synaptic potential (fEPSP) in the LPS group decreased, whereas in 7NI-LPS group they increased. CONCLUSION: It is suggested that inhibition of nNOS by 7NI improves the deleterious effects of LPS by reducing NO metabolites and the brain tissues oxidative damage.

Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole.

Inflammation and oxidative stress have important roles in memory impairment. The effect of 7-nitroindazole (7NI) on lipopolysaccharide (LPS)-induced memory impairment was investigated. Rats were used, divided into four groups that were treated as follows: (1) control (saline); (2) LPS; (3) 7NI-LPS; and (4) 7NI before passive avoidance (PA). In the LPS group, the latency for entering the dark compartment was shorter than in the controls (p < 0.01 and p < 0.001); while in the 7NI-LPS group, it was longer than in the LPS group (p < 0.01 and p < 0.001). Malondialdehyde (MDA) and nitric oxide (NO) metabolite concentrations in the brain tissues of the LPS group were higher than in the controls (p < 0.001 and p < 0.05); while in the 7NI-LPS group, they were lower than in the LPS group (p < 0.001 and p < 0.05, respectively). The thiol content in the brain of the LPS group was lower than in the controls (p < 0.001); while in the 7NI-LPS group, it was higher than in the LPS group (p < 0.001). It is suggested that brain tissue oxidative damage and NO elevation have a role in the deleterious effects of LPS on memory retention that are preventable using 7NI.

Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole / O déficit de memória induzido por lipossacarídeos em ratos é prevenido por nitroindazol

Inflammation and oxidative stress have important roles in memory impairment. The effect of 7-nitroindazole (7NI) on lipopolysaccharide (LPS)-induced memory impairment was investigated. Rats were used, divided into four groups that were treated as follows: (1) control (saline); (2) LPS; (3) 7NI-LPS; and (4) 7NI before passive avoidance (PA). In the LPS group, the latency for entering the dark compartment was shorter than in the controls (p < 0.01 and p < 0.001); while in the 7NI-LPS group, it was longer than in the LPS group (p < 0.01 and p < 0.001). Malondialdehyde (MDA) and nitric oxide (NO) metabolite concentrations in the brain tissues of the LPS group were higher than in the controls (p < 0.001 and p < 0.05); while in the 7NI-LPS group, they were lower than in the LPS group (p < 0.001 and p < 0.05, respectively). The thiol content in the brain of the LPS group was lower than in the controls (p < 0.001); while in the 7NI-LPS group, it was higher than in the LPS group (p < 0.001). It is suggested that brain tissue oxidative damage and NO elevation have a role in the deleterious effects of LPS on memory retention that are preventable using 7NI.

Inflamação e estresse oxidativo tem importante papel no déficit de memória. O efeito do 7-nitroindazol (7NI) no déficit de memória induzido por lipossacarídeos (LPS) foi investigado. Foram utilizados ratos que foram divididos em quatro grupos e tratados da seguinte maneira: (1) controles (solução salina); (2) LPS; (3) 7NI-LPS; e (4) 7NI antes da esquiva passiva (PA). No grupo LPS, a latência para entrar no compartimento escuro foi mais curta que nos controles (p < 0,01 e p < 0,001); enquanto no grupo 7NI-LPS, a latência foi maior que aquela do grupo LPS (p < 0,01 e p < 0,001). Concentrações de malondialdeído (MDA) e metabólitos do ácido nítrico (NO) no tecido cerebral do grupo LPS foram maiores que aquelas dos controles (p < 0,001 e p < 0,05); enquanto no grupo 7NI-LPS, as concentrações foram menores do que no grupo LPS (p < 0,001 e p < 0,05, respectivamente). O conteúdo cerebral de tiol no grupo LPS foi menos do que nos controles (p < 0,001); enquanto no grupo 7NI-LPS, este conteúdo foi maior que no grupo LPS (p < 0,001). Sugere-se que o dano oxidativo cerebral e o aumento de NO tenham um papel nos efeitos deteriorativos dos LPS na memória de retenção, e que isto possa ser prevenido com o uso de 7NI.