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Depression is the fourth most serious disease in the world. Left untreated, it is a cause of suicide attempts, emergence or exacerbation worsening of serious diseases, bodily and mental disorders, as well as increased risk of cardiovascular diseases, stroke, diabetes, and obesity, as well as endocrine and neurological diseases. Frequent coexistence of depression and other diseases requires the simultaneous use of several drugs from different therapeutic groups, which very often interact and intensify comorbidities, sometimes unrelated mechanisms. Sufficient awareness of potential drug interactions is critical in clinical practice, as it allows both to avoid disruption of proper pharmacotherapy and achieve substantive results. Therefore, this review aims to analyze the interactions of antidepressants with other concomitant medications. Against the backdrop of experimental research and a thorough analysis of the up-to-date literature, the authors discuss in detail the mechanisms and effects of action of individual drug interactions and adaptogens, including the latest antidepressants.
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Antidepresivos , Interacciones Farmacológicas , Humanos , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Multimorbilidad , Animales , PolifarmaciaRESUMEN
Diabetes, a widespread chronic metabolic disease, is projected to affect 783 million people globally by 2045. Recent studies emphasize the neuroprotective potential of dipeptidyl peptidase 4 (DPP4i) inhibitors, pointing toward a promising avenue for intervention in addressing cognitive challenges associated with diabetes. Due to limited data on the effect of DPP4i on brain pathways involved in diabetes-related neurocognitive disorders, the decision was made to conduct this study to fill existing knowledge gaps on this topic. The primary aim of our study was to evaluate the potential of DPP4 inhibitors (DPP4i) in preventing cognitive decline in mice with type 2 diabetes (T2D), placing special emphasis on gaining insight into the complex molecular mechanisms underlying this action. We examined drug efficacy in modulating neurotrophic factors, calcium levels, and the expression of key genes (HIF1α, APP, Arc) crucial for neural plasticity. Conducting cognitive assessments with the hole board and passive avoidance tests, we discerned a remarkable influence of short-term gliptin usage on the limiting progress of cognitive dysfunction in diabetic mice. The administration of DPP4 inhibitors led to heightened neurotrophin levels, increased HIF1α in the prefrontal cortex, and a significant elevation in Arc mRNA levels. Our findings reveal that DPP4 inhibitors effectively limit the progression of diabetes-related cognitive disorders. This breakthrough discovery not only opens new research avenues but also constitutes a potential starting point for creating innovative strategies for the treatment of central nervous system disorders focused on improving cognitive abilities.
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In this research, twenty-four hydrazide-hydrazones of 2,4-dihydroxybenzoic acid were designed, synthesized, and subjected to in vitro and in vivo bioactivity studies. The chemical structure of the obtained compounds was confirmed by spectral methods. Antimicrobial activity screening was performed against a panel of microorganisms for all synthesized hydrazide-hydrazones. The performed assays revealed the interesting antibacterial activity of a few substances against Gram-positive bacterial strains including MRSA-Staphylococcus aureus ATCC 43300 (compound 18: 2,4-dihydroxy-N-[(2-hydroxy-3,5-diiodophenyl)methylidene]benzohydrazide-Minimal Inhibitory Concentration, MIC = 3.91 µg/mL). In addition, we performed the in vitro screening of antiproliferative activity and also assessed the acute toxicity of six hydrazide-hydrazones. The following human cancer cell lines were used: 769-P, HepG2, H1563, and LN-229, and the viability of the cells was assessed using the MTT method. The HEK-293 cell line was used as a reference line. The toxicity was tested in vivo on Danio rerio embryos using the Fish Embryo Acute Toxicity (FET) test procedure according to OECD No. 236. The inhibitory concentration values obtained in the in vitro test showed that N-[(4-nitrophenyl)methylidene]-2,4-dihydroxybenzhydrazide (21) inhibited cancer cell proliferation the most, with an extremely low IC50 (Inhibitory Concentration) value, estimated at 0.77 µM for LN-229. In addition, each of the compounds tested was selective against cancer cell lines. The compounds with a nitrophenyl substituent were the most promising in terms of inhibition cancer cell proliferation. The toxicity against zebrafish embryos and larvae was also very low or moderate.
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Antineoplásicos , Hidrazonas , Animales , Humanos , Hidrazonas/farmacología , Hidrazinas/farmacología , Hidrazinas/química , Células HEK293 , Pez Cebra , Relación Estructura-Actividad , Pruebas de Sensibilidad Microbiana , Antineoplásicos/químicaRESUMEN
Alzheimer's is a prevalent, progressive neurodegenerative disease marked by cognitive decline and memory loss. The disease's development involves various pathomechanisms, including amyloid-beta accumulation, neurofibrillary tangles, oxidative stress, inflammation, and mitochondrial dysfunction. Recent research suggests that antidiabetic drugs may enhance neuronal survival and cognitive function in diabetes. Given the well-documented correlation between diabetes and Alzheimer's disease and the potential shared mechanisms, this review aimed to comprehensively assess the potential of new-generation anti-diabetic drugs, such as GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, as promising therapeutic approaches for Alzheimer's disease. This review aims to comprehensively assess the potential therapeutic applications of novel-generation antidiabetic drugs, including GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, in the context of Alzheimer's disease. In our considered opinion, antidiabetic drugs offer a promising avenue for groundbreaking developments and have the potential to revolutionize the landscape of Alzheimer's disease treatment.
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Eating disorders and diabetes mellitus are distinct yet closely linked health conditions, presenting distinct challenges in terms of care and management. Eating disorders encompass a spectrum of mental health disorders characterized by abnormal eating behaviors and disruptions in weight regulation. Research indicates that individuals with diabetes might be at an elevated risk of developing eating disorders. The necessity to adhere to specific dietary guidelines, monitor blood sugar levels vigilantly, and manage drug administration can collectively contribute to the emergence of detrimental attitudes toward food and body image. On the other hand, incorrect eating behaviors such as binge eating and purging can disrupt blood sugar control, significantly impacting the development and management of diabetes. This intricate relationship emphasizes the crucial necessity for a comprehensive understanding and specialized care to effectively address the dual challenges faced by individuals dealing with both diabetes and eating disorders. This paper represents the inaugural comprehensive review delving into the intricate connection between eating disorders and diabetes, thereby illuminating previously under-researched areas. The insights gleaned from this review may contribute to developing integrated interventions that aim to improve the overall well-being and quality of life for individuals grappling with the complexities of eating disorders and diabetes.
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The study aimed to evaluate the antidepressant-like effects of an imipramine-zinc (IMI-Zn) complex compound on mice and assess the level of oxidative stress parameters. The research also investigated whether the IMI-Zn complex showed superior antidepressant activity compared to individual treatments of both compounds at effective doses and their joint administration at subtherapeutic doses. The study was conducted on mice. Forced swim (FST), tail suspension (TST), and locomotor activity tests were used for behavioral studies. The results demonstrated the IMI-Zn complex's dose-dependent antidepressant potential when orally administered to mice. Its efficacy was similar to the separate administration of therapeutic doses of imipramine (IMI) and zinc (Zn) and their joint administration at subtherapeutic doses. Moreover, subjecting mice to acute stress did not significantly affect the activity of on glutathione peroxidase (GPX), glutathione reductase (GR), and total antioxidant status (TAS), possibly due to the short exposure time to the stress stimulus. By developing the IMI-Zn complex, it might be possible to simplify the treatment approach, potentially improving patient compliance by combining the therapeutic effects of both IMI and Zn within a single compound, thus addressing one of the contributing factors to non-compliance in depression therapy. The IMI-Zn complex could be a valuable strategy to optimize therapeutic outcomes and balance efficacy and tolerability.
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In recent years, there has been a significant increase in the concomitant incidence of Hashimoto's thyroiditis (HT) and polycystic ovary syndrome (PCOS), both in terms of incidence, etiology, and clinical consequences. PCOS patients suffering from autoimmune thyroid diseases show insulin resistance, impaired glucose tolerance, weight gain, and metabolic and reproductive complications. Studies have shown that chronic stress and its consequence, i.e. oxidative stress, play an important role in the pathomechanism of both disorders. It has also been shown that long-term exposure to stress triggers biological mechanisms, in particular related to the regulation of the inflammatory cascade, which plays a key role in autoimmune diseases. The paper is a review of the literature on the role of chronic stress, oxidative stress, and immune processes in the pathogenesis of HT and PCOS. In addition, the review is a source of knowledge about the treatment of these diseases, and in particular the use of antioxidants in therapeutic management.
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Enfermedades Autoinmunes , Enfermedad de Hashimoto , Enfermedades del Sistema Inmune , Síndrome del Ovario Poliquístico , Femenino , Humanos , Estrés OxidativoRESUMEN
In recent years, there has been a significant increase in depression, which is related to, among other things, the COVID-19 pandemic. Depression can be fatal if not treated or if treated inappropriately. Depression is the leading cause of suicide attempts. The disease is multifactorial, and pharmacotherapy often fails to bring satisfactory results. Therefore, increasingly more importance is attached to the natural healing substances and nutrients in food, which can significantly affect the therapy process and prevention of depressive disorders. A proper diet is vital to preventing depression and can be a valuable addition to psychological and pharmacologic treatment. An inadequate diet may reduce the effectiveness of antidepressants or increase their side effects, leading to life-threatening symptoms. This study aimed to review the literature on the pathogenesis of the development and treatment of depression, with particular emphasis on dietary supplements and the role of nutrition in the prevention and treatment of depressive disorders.
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Diabetes causes a variety of molecular changes in the brain, making it a real risk factor for the development of cognitive dysfunction. Complex pathogenesis and clinical heterogeneity of cognitive impairment makes the efficacy of current drugs limited. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) gained our attention as drugs with potential beneficial effects on the CNS. In the present study, these drugs ameliorated the cognitive impairment associated with diabetes. Moreover, we verified whether SGLT2i can mediate the degradation of amyloid precursor protein (APP) and modulation of gene expression (Bdnf, Snca, App) involved in the control of neuronal proliferation and memory. The results of our research proved the participation of SGLT2i in the multifactorial process of neuroprotection. SGLT2i attenuate the neurocognitive impairment through the restoration of neurotrophin levels, modulation of neuroinflammatory signaling, and gene expression of Snca, Bdnf, and App in the brain of diabetic mice. The targeting of the above-mentioned genes is currently seen as one of the most promising and developed therapeutic strategies for diseases associated with cognitive dysfunction. The results of this work could form the basis of a future administration of SGLT2i in diabetics with neurocognitive impairment.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Ratones , Animales , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucosa , Sodio/uso terapéuticoRESUMEN
Neurological diseases are recognized as major causes of disability and mortality worldwide. Due to the dynamic progress of diseases such as Alzheimer's disease (AD), Parkinson's Disease (PD), Schizophrenia, Depression, and Multiple Sclerosis (MD), scientists are mobilized to look for new and more effective methods of interventions. A growing body of evidence suggests that inflammatory processes and an imbalance in the composition and function of the gut microbiome, which play a critical role in the pathogenesis of various neurological diseases and dietary interventions, such as the Mediterranean diet the DASH diet, or the ketogenic diet can have beneficial effects on their course. The aim of this review was to take a closer look at the role of diet and its ingredients in modulating inflammation associated with the development and/or progression of central nervous system diseases. Presented data shows that consuming a diet abundant in fruits, vegetables, nuts, herbs, spices, and legumes that are sources of anti-inflammatory elements such as omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics while avoiding foods that promote inflammation, create a positive brain environment and is associated with a reduced risk of neurological diseases. Personalized nutritional interventions may constitute a non-invasive and effective strategy in combating neurological disorders.
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Enfermedad de Alzheimer , Dieta Mediterránea , Humanos , Dieta , Vitaminas , Encéfalo , Verduras , InflamaciónRESUMEN
During the COVID-19 pandemic, an increase in the incidence of overweight and obesity in children was observed. It appears that unhealthy food choices, an unbalanced diet, and a sedentary lifestyle, as well as experiencing stress related to the pandemic, may be contributing to this disturbing trend. Chronic stress is a significant factor contributing to eating disorders and obesity in youngsters, involving medical, molecular, and psychological elements. Individuals under chronic stress often focus on appearance and weight, leading to negative body image and disrupted relationships with food, resulting in unhealthy eating behaviors. Chronic stress also impacts hormonal balance, reducing the satiety hormone leptin and elevating the appetite-stimulating hormone ghrelin, fostering increased hunger and uncontrolled snacking. Two systems, the hypothalamic-pituitary-adrenal axis and the sympathetic system with the adrenal medulla, are activated in response to stress, causing impaired secretion of noradrenaline and cortisol. Stress-related obesity mechanisms encompass oxidative stress, neuroinflammation, insulin resistance, and neurohormonal and neurotransmission disorders. Stress induces insulin resistance, elevating obesity risk by disrupting blood sugar regulation and fat storage. Stress also affects the gut microbiome, potentially influencing chronic inflammation and metabolic processes linked to obesity. In conclusion, chronic stress is a multifaceted risk factor for eating disorders and obesity in children, necessitating a comprehensive understanding of effective preventive and intervention strategies amid the escalating prevalence of childhood overweight and obesity.
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COVID-19 , Resistencia a la Insulina , Obesidad Infantil , Niño , Humanos , Adolescente , Obesidad Infantil/epidemiología , Sistema Hipotálamo-Hipofisario , Pandemias , COVID-19/epidemiología , Sistema Hipófiso-Suprarrenal , Conducta AlimentariaRESUMEN
One of the most important therapies of malignant neoplasms, which are the second cause of death worldwide, is focused on the inhibition of pathological angiogenesis within the tumor. Therefore, the searching for the efficacious and relatively inexpensive small-molecule inhibitors of this process is essential. In this research, the anti-angiogenic potential of N-substituted-4-methylbenzenesulphonyl hydrazone, possessing antiproliferative activity against cancer cells, was tested. For this purpose, an intersegmental vessel (ISV) angiogenesis assay was performed using 6 hpf (hours post fertilization), 12 hpf and 24 hpf embryos of zebrafish transgenic strain, Tg(fli1: EGFP). They were incubated with different concentrations of tested molecule and after 24 h the development of intersegmental vessels of the trunk was analysed. In turn, the acute toxicity study in the zebrafish model was mainly conducted on strain AB, using the OECD-approved and recommended fish embryo acute toxicity test (FET) procedure. The results showed the moderate toxicity of N-[(3-chloro-4-methoxyphenyl)methylidene]-4-methylbenzenesulphonohydrazide in above-mentioned model with the LC50 value calculated at 23.04 mg/L. Moreover, newly synthesized molecule demonstrated the anti-angiogenic potential proved in Tg(fli1: EGFP) zebrafish model, which may be promising for the therapy of neoplastic tumors as well as other diseases related to pathological angiogenesis, such as age-related macular degeneration and diabetic retinopathy.
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The study aimed to evaluate the safety and pharmacological activity Amaryllidaceae, Lycopodiaceae alkaloids and coumarins obtained from Narcissus triandrus L., Lycopodium clavatum L., Lycopodium annotinum L., Huperzia selago L. and Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. In the in vivo studies. The influence of the tested compounds on the central nervous system of rats was assessed in behavioral tests (locomotor activity, Y-maze, passive avoidance). In order to investigate the mechanisms of action, biochemical determinations were performed (AChE activity, BChE activity, IL-1ß, IL-6 concentration). In order to assess safety, the concentrations of AST, ALT, GGT and urea and creatinine were determined. The results of the conducted studies indicate a high safety profile of the tested compounds. Behavioral tests showed that they significantly improved rodent memory in a passive avoidance test. The results of biochemical studies showed that by reducing the activity of AChE and BChE and lowering the concentration of IL-1ß and IL-6, the coumarin-rich Angelica dahurica extract shows the most promising potential for future therapeutic AD strategies.
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The ketogenic diet (KD) is a high-fat, low-carbohydrate and adequate-protein diet that has gained popularity in recent years in the context of neurological diseases (NDs). The complexity of the pathogenesis of these diseases means that effective forms of treatment are still lacking. Conventional therapy is often associated with increasing tolerance and/or drug resistance. Consequently, more effective therapeutic strategies are being sought to increase the effectiveness of available forms of therapy and improve the quality of life of patients. For the moment, it seems that KD can provide therapeutic benefits in patients with neurological problems by effectively controlling the balance between pro- and antioxidant processes and pro-excitatory and inhibitory neurotransmitters, and modulating inflammation or changing the composition of the gut microbiome. In this review we evaluated the potential therapeutic efficacy of KD in epilepsy, depression, migraine, Alzheimer's disease and Parkinson's disease. In our opinion, KD should be considered as an adjuvant therapeutic option for some neurological diseases.
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Dieta Cetogénica , Epilepsia , Microbioma Gastrointestinal , Trastornos Migrañosos , Humanos , Calidad de VidaRESUMEN
Many relevant studies, as well as clinical practice, confirm that untreated diabetes predisposes the development of neuroinflammation and cognitive impairment. Having regard for the fact that PPARγ are widely distributed in the brain and PPARγ ligands may regulate the inflammatory process, the anti-inflammatory potential of the PPARγ agonist, pioglitazone, was assessed in a mouse model of neuroinflammation related with diabetes. In this regard, the biochemical and molecular indicators of neuroinflammation were determined in the hippocampus and prefrontal cortex of diabetes mice. The levels of cytokines (IL-1ß, IL-6, and TNF) and the expression of genes (Tnfrsf1a and Cav1) were measured. In addition, behavioral tests such as the open field test, the hole-board test, and the novel object recognition test were conducted. A 14-day treatment with pioglitazone significantly decreased IL-6 and TNFα levels in the prefrontal cortex and led to the downregulation of Tnfrsf1a expression and the upregulation of Cav1 expression in both brain regions of diabetic mice. Pioglitazone, by targeting neuroinflammatory signaling, improved memory and exploratory activity in behavioral tests. The present study provided a potential theoretical basis and therapeutic target for the treatment of neuroinflammation associated with diabetes. Pioglitazone may provide a promising therapeutic strategy in diabetes patients with muffled of behavioral activity.
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Diabetes Mellitus Experimental , Enfermedades Neuroinflamatorias , PPAR gamma , Pioglitazona , Animales , Caveolina 1/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Modelos Animales de Enfermedad , Interleucina-6/metabolismo , Ratones , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/prevención & control , PPAR gamma/agonistas , Pioglitazona/farmacología , Pioglitazona/uso terapéutico , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Exposure to chronic stress leads to disturbances in glucose metabolism in the brain, and changes in the functioning of neurons coexisting with the development of depression. The detailed molecular mechanism and cerebral gluconeogenesis during depression are not conclusively established. The aim of the research was to assess the expression of selected genes involved in cerebral glucose metabolism of mice in the validated animal paradigm of chronic stress. To confirm the induction of depression-like disorders, we performed three behavioral tests: sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST). In order to study the cerebral glucose metabolism of the brain, mRNA levels of the following genes were determined in the prefrontal cortex of mice: Slc2a3, Gapdh, Ldha, Ldhb, and Pkfb3. It has been shown that exogenous, chronic administration of corticosterone developed a model of depression in behavioral tests. There were statistically significant changes in the mRNA level of the Slc2a3, Ldha, Gapdh, and Ldhb genes. The obtained results suggest changes in cerebral glucose metabolism as a process of adaptation to stressful conditions, and may provide the basis for introducing new therapeutic strategies for chronic stress-related depression.
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Diabetes is a chronic disease leading to memory difficulties and deterioration of learning abilities. The previous studies showed that modulation of inflammatory pathways in the diabetic brain may reduce dysfunction or cell death in brain areas which are important for control of cognitive function. In the present study, we investigated the neuroprotective actions of newly synthesized adamantane derivatives on diabetes-induced cognitive impairment in mice. Our study relied on the fact that both vildagliptin and saxagliptin belong to DPP4 inhibitors and, contain adamantanyl group. Efficacy of tested compounds at reversing diabetes-induced different types of memory impairment was evaluated with the use of selected behavioural tests. The following neuroinflammatory indicators were also analyzed: neuroinflammatory indicators and the expression of genes involved in the inflammatory response of brain (Cav1, Bdnf). Our study demonstrated that new adamantane derivatives, similarly to DPP4 inhibitors, can restrict diabetes-induced cognitive deficits. We demonstrated that the overexpression of GLP-1-glucagon-like peptide as well as Bdnf, Cav1 genes translate into central blockade of pro-inflammatory synthesis of cytokines and significantly improvement on memory performance in diabetes mice. Newly synthesized adamantane derivatives might have important roles in prevention and treatment of cognitive impairment by inflammatory events in patients with diabetes or related diseases.
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Adamantano , Disfunción Cognitiva , Diabetes Mellitus , Inhibidores de la Dipeptidil-Peptidasa IV , Adamantano/farmacología , Adamantano/uso terapéutico , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Dopaminérgicos , Humanos , Inflamación/tratamiento farmacológico , Mediadores de Inflamación , Ratones , Plasticidad NeuronalRESUMEN
The brain is the most vulnerable organ to glucose fluctuations, as well as inflammation. Considering that cognitive impairment might occur at the early stage of diabetes, it is very important to identify key markers of early neuronal dysfunction. Our overall goal was to identify neuroinflammatory and molecular indicators of early cognitive impairment in diabetic mice. To confirm cognitive impairment in diabetic mice, series of behavioral tests were conducted. The markers related to cognitive decline were classified into the following two groups: Neuroinflammatory markers: IL-1ß, IL-6, tumor necrosis factor-α (TNF-α) and genetic markers (Bdnf, Arc, Egr1) which were estimated in brain regions. Our studies showed a strong association between hyperglycemia, hyperinsulinemia, neuroinflammation, and cognitive dysfunction in T2DM mice model. Cognitive impairment recorded in diabetes mice were associated not only with increased levels of cytokines but also decreased Arc and Egr1 mRNA expression level in brain regions associated with learning process and memory formation. The results of our research show that these indicators may be useful to test new forms of treatment of early cognitive dysfunction associated not only with diabetes but other diseases manifesting this type of disorders. The significant changes in Arc and Egr1 gene expression in early stage diabetes create opportunities it possible to use them to track the progression of CNS dysfunction and also to differential disease diagnosis running with cognitive impairment.
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Biomarcadores , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Diabetes Mellitus Experimental/complicaciones , Susceptibilidad a Enfermedades , Mediadores de Inflamación/metabolismo , Animales , Glucemia , Disfunción Cognitiva/psicología , Citocinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Hipocampo/fisiopatología , Insulina/sangre , Aprendizaje , Masculino , Aprendizaje por Laberinto , Memoria , Ratones , Actividad Motora , Corteza Prefrontal/metabolismoRESUMEN
Chronic or recurrent stress is associated with reactive oxygen species (ROS) overproduction and can lead to oxidative damage, which plays important roles in neurodegenerative diseases. Mito - TEMPO is an antioxidant targeted at mitochondria. The aim of the presented study was to assess antidepressant and antioxidant efficacy of Mito - TEMPO administered alone or with fluoxetine in mice exposed to chronic stress. The evaluation of the antidepressant-like activity was based on forced swimming test (FST) and tail suspension test (TST). In order to evaluate the antioxidant potential, the level of mRNA expression of Adora1, Ogg1, Msra, Nrf2 and Tfam in the hippocampus of mice was determined. Behavioural research data showed the antidepressant effect of fluoxetine and Mito - TEMPO administered to mice alone and in combination. The molecular research results indicate a significant impact of chronic stress on the oxidation-reduction balance and an antioxidant effect of Mito - TEMPO. The results obtained in the study suggest that Mito - TEMPO protects DNA against oxidative damage and may be beneficial in the way of cellular function improvement under the conditions of chronic stress. Adora1, Msra, Nrf2 and Tfam genes may be involved in mediating the antioxidant effect of the combined treatment with fluoxetine and Mito - TEMPO.
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Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Fluoxetina/farmacología , Hipocampo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Estrés Psicológico/metabolismo , Animales , Depresión/metabolismo , Modelos Animales de Enfermedad , Quimioterapia Combinada , Hipocampo/metabolismo , Masculino , RatonesRESUMEN
Cancer treatment remains a serious challenge worldwide. Thus, finding novel antitumour agents is of great importance. In the present study, nine new benzenesulphonohydrazide derivatives (1-9) were synthesized, and the chemical structures of the obtained compounds were confirmed by spectral analysis methods, including IR, 1H nuclear magnetic resonance (NMR) and 13C NMR. Experimental lipophilicity values were established using reversed phase-high performance thin layer chromatography. The antiproliferative activity of the synthesized compounds was tested against three tumour cell lines (769-P, HepG2 and NCI-H2170) and one normal cell line (Vero). Among the newly developed molecules, compound 4 exhibited generally the highest cytotoxicity across all tumour cell lines, and it was highly selective. However, higher selectivity towards the tested cancer cell lines was observed using compound 2, when compared with compound 4, which also exhibited significant antiproliferative activity against these tumour cells. In 769-P cells, compounds 5 and 6 were the most selective among all tested compounds. Compound 5 exhibited high cytotoxicity with an estimated IC50 value of 1.94 µM. In the NCI-H2170 cell line, compound 7 was the most cytotoxic and the most selective. In brief, the combination of fluorine and bromine substituents at the phenyl ring showed the most promising results, exerting high cytotoxicity and selectivity towards cancer cells. The renal adenocarcinoma cell line (769-P) appeared to be the most sensitive to the anticancer properties of the novel benzenesulphonohydrazones.