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RATIONALE: Depression is the most prevalent psychiatric disorder worldwide. Although numerous antidepressant treatments are available, there is a serious clinical concern due to their severe side effects and the fact that some depressed patients are resistant to them. Lithium is the drug of choice for bipolar depression and has been used as adjunct therapy with other groups of antidepressants. OBJECTIVES: The present study aims to investigate the effect of lithium augmentation with cerebrolysin on the neurochemical, behavioral and histopathological alterations induced in the reserpine model of depression. METHODS: The animals were divided into control and reserpine-induced model of depression. The model animals were further divided into rat model of depression, rat model treated with lithium, rat model treated with cerebrolysin and rat model treated with a combination of lithium and cerebrolysin. RESULTS: Treatment with lithium, cerebrolysin, or their combination alleviated most of the changes in behavior, oxidative stress parameters, acetylcholinesterase and monoamines in the cortex and hippocampus of the reserpine-induced model of depression. It also improved the alterations in brain-derived neurotrophic factor (BDNF) and histopathology induced by reserpine. CONCLUSIONS: The augmentation of lithium with cerebrolysin showed a clear beneficial effect in the present model of depression suggesting the use of cerebrolysin as an adjuvant in antidepressant treatment.
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Aminoácidos , Depresión , Litio , Humanos , Ratas , Animales , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Reserpina , Acetilcolinesterasa , Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del EncéfaloRESUMEN
Photobiomodulation (PBM) of deep brain structures through transcranial infrared irradiation might be an effective treatment for Parkinson's disease (PD). However, the mechanisms underlying this intervention should be elucidated to optimize the therapeutic outcome and maximize therapeutic efficacy. The present study aimed at investigating the oxidative stress-related parameters of malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) and the enzymatic activities of sodium-potassium-ATPase (Na+, K+-ATPase), Acetylcholinesterase (AChE), and monoamine oxidase (MAO) and monoamine levels (dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the midbrain and striatum of reserpine-induced PD in an animal model treated with PBM. Furthermore, the locomotor behavior of the animals has been determined by the open field test. Animals were divided into three groups; the control group, the PD-induced model group, and the PD-induced model treated with the PBM group. Non-invasive treatment of animals for 14 days with 100 mW, 830 nm laser has demonstrated successful attainment in the recovery of oxidative stress, and enzymatic activities impairments induced by reserpine (0.2 mg/kg) in both midbrain and striatum of adult male Wistar rats. PBM also improved the decrease in DA, NE, and 5-HT in the investigated brain regions. On a behavioral level, animals showed improvement in their locomotion activity. These findings have shed more light on some mechanisms underlying the treatment potential of PBM and displayed the safety, easiness, and efficacy of PBM treatment as an alternative to pharmacological treatment for PD.
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Terapia por Luz de Baja Intensidad , Trastornos Parkinsonianos , Ratas , Masculino , Animales , Reserpina/farmacología , Ratas Wistar , Serotonina , Acetilcolinesterasa , Mesencéfalo , Dopamina , Adenosina Trifosfatasas , Modelos Animales de EnfermedadRESUMEN
Depression, a devastating brain illness, necessitates the exploration of novel antidepressant treatments. We evaluated the antidepressant effects of free curcumin, zinc oxide nanoparticles (ZnO NPs), and curcumin-conjugated zinc oxide nanoparticles (Zn(cur)O NPs). The nanoformulations were extensively characterized using advanced techniques. An acute toxicity study ensured the safety of Zn(cur)O NPs. Rats were assigned to one of five groups: control, reserpine-induced depression model, treatment with ZnO NPs, free curcumin, or Zn(cur)O NPs. Behavioral assessments (forced swimming test [FST] and open-field test [OFT]) and neurochemical analyses were conducted. Zn(cur)O NPs exhibited superior efficacy in ameliorating reserpine-induced behavioral and neurochemical effects compared to free curcumin and ZnO NPs. The reserpine-induced model displayed reduced motor activity, swimming time, and increased immobility time in the FST and OFT. Treatment with Zn(cur)O NPs 45 mg/kg significantly improved motor activity and reduced immobility time. Furthermore, Zn(cur)O NPs decreased malondialdehyde (MDA) levels while increasing reduced glutathione (GSH) and catalase (CAT) levels. Additionally, concentrations of serotonin (5-HT) and norepinephrine (NE) increased. In conclusion, curcumin-conjugated zinc oxide nanoparticles demonstrate potent antidepressant effects, alleviating depressive-like behavior in rats. These findings support Zn(cur)O NPs as a promising therapeutic strategy for depression management, warranting further investigation and clinical validation.
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Metal nanoparticles, in general, and silver nanoparticles (AgNPs), in particular, have been the focus of numerous studies over the last two decades. Recently, the green synthesis of metal nanoparticles has been favored over chemical synthesis due to its low toxicity and easy preparation. The present study aims to investigate the dose-dependent toxicity of green synthesized AgNPs on rats' brains. Thirty-four Wistar male rats were divided into four groups. The first, second, and third groups were administered for 14 days with three different doses (0.5, 5, and 10 mg/kg) of AgNPs, respectively. The fourth group, which served as a control group, was given normal saline for the same period. The toxicity of the green synthesized AgNPs on the cortical and hippocampal levels of the oxidative stress markers (MDA, NO, and GSH) as well as the activity of acetylcholinesterase (AchE) and the monoamine neurotransmitters (DA, NE, and 5H-T) were investigated. AgNPs showed minimal oxidative stress in the cortex and hippocampus for the administered doses. However, AgNPs showed an inhibitory effect on AchE activity in a dose-dependent manner and a decrease in the 5H-T and NE levels. The green synthesized AgNPs showed an ultrastructural change in the cellular membranes of the neurons. The green synthesis of AgNPs has reduced their cytotoxic oxidative effects due to their capping with biologically compatible and boosting molecules such as flavonoids. However, another neurotoxicity was observed in a dose-dependent manner.
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Nanopartículas del Metal , Plata , Ratas , Animales , Masculino , Plata/química , Ratas Wistar , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Acetilcolinesterasa , Extractos Vegetales/farmacología , Encéfalo , Tecnología Química VerdeRESUMEN
Objective: The current study evaluates the effect of metformin (MET) and /or alpha lipoic acid (ALA) on hypothyroidism and its adverse effects on the cardiac, renal, and, hepatic functions in rats. Materials and methods: Rats were divided into five groups: control, rat model of hypothyroidism induced by propylthiouracil (PTU), rat model of hypothyroidism treated with MET, rat model of hypothyroidism treated with ALA, and rat model of hypothyroidism treated with MET and ALA. At the end of the experiment, body weight gain was determined and the blood samples were collected from orbital plexus to measure the serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) by ELISA, glucose level, the activities of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and the levels of urea and creatinine spectrophotometrically. Results: Rat model of hypothyroidism revealed a significant decrease in T4 (p < 0.001) and T3 (p < 0.001) and a significant increase in TSH (p < 0.005). This was accompanied by a significant decrease in the body weight gain (p < 0.025) and a significant increase in LDH (p < 0.001), CK-MB (p < 0.001) AST (p < 0.01), ALT (p < 0.016), ALP (p < 0.001), glucose (p < 0.001), urea (p < 0.001) and creatinine (p < 0.001). MET restored T4, T3 and TSH to control values. Treatment with ALA restored T3 and TSH levels. Treatment with Met and /or ALA reduced the levels of glucose, urea and creatinine and the activities of LDH, CK-MB, AST, ALT, and ALP to control-like values. Only ALA improved the reduced body weight gain induced by hypothyroidism. Conclusion: The present findings indicate the ameliorative effects of MET and /or ALA on hypothyroidism and its adverse effects on cardiac, renal and hepatic functions. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-022-01063-7.
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The cardiotoxicity of chemotherapeutic drugs as cisplatin has become a major issue in recent years. The present study investigates the efficacy of curcumin nanoparticles against the cardiotoxic effects of cisplatin by assessment of oxidative stress parameters, Na+,K+-ATPase, acetylcholinesterase (AchE) and tumor necrosis factor-alpha (TNF-α) in cardiac tissue in addition to serum lactate dehydrogenase (LDH). Rats were divided into three groups: control rats that received saline for 14 days; cisplatin-treated rats that received a single intraperitoneal (i.p.) injection of cisplatin (12 mg/kg) followed by a daily oral administration of saline (0.9%) for 14 days and rats treated with a single i.p. injection of cisplatin (12 mg/kg) followed by a daily oral administration of curcumin nanoparticles (50 mg/kg) for 14 days. Cisplatin resulted in a significant increase in lipid peroxidation, nitric oxide (NO), and TNF-α and a significant decrease in reduced glutathione (GSH) levels and Na+, K+- ATPase activity. Moreover, significant increases in cardiac AchE and serum lactate dehydrogenase activities were recorded. Treatment of cisplatin-injected animals with curcumin nanoparticles ameliorated all the alterations induced by cisplatin in the heart of rats. This suggests that curcumin nanoparticles can be used as an important therapeutic adjuvant in chemotherapeutic and other toxicities mediated by oxidative stress and inflammation.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Curcumina/farmacología , Cardiopatías/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Nanopartículas , Acetilcolinesterasa/metabolismo , Animales , Cisplatino , Modelos Animales de Enfermedad , Proteínas Ligadas a GPI/metabolismo , Cardiopatías/inducido químicamente , Cardiopatías/metabolismo , Cardiopatías/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The current aim is to evaluate the effect of ashwagandha root extract (AE) on the neurochemical changes induced in the cortex and hippocampus as a consequence of thyroid dysfunction induced by propylthiouracil (PTU). Male Wistar rats were divided into; control, AE treated rats, rat model of hypothyroidism and rat model of hypothyroidism treated with either AE or L-thyroxine (T4) for 1 month. Rat model of hypothyroidism showed a significant decrease in serum levels of tri-iodothyronine (T3) and T4 and a significant increase in cortical and hippocampal lipid peroxidation (MDA), nitric oxide (NO), superoxide dismutase (SOD) and catalase (CAT). However, reduced glutathione (GSH) decreased significantly. This was associated with a significant increase in hippocampal tumor necrosis factor-α (TNF-α) and cortical dopamine levels. Both L-thyroxine and AE restored T3 and T4 levels. In the hippocampus L-Thyroxine prevented the increase in MDA and restored GSH but failed to restore the increased NO and TNF-α. In the cortex L-thyroxine didn't change the increased MDA and NO and the decreased GSH induced by PTU. L-thyroxine increased cortical and hippocampal SOD and CAT. AE prevented the increased hippocampal MDA, NO and TNF-α and the decreased GSH level induced by PTU. In the cortex AE failed to restore MDA and NO but prevented the decrease in GSH. The increase in cortical dopamine level induced by PTU was ameliorated by L-thyroxine and improved by AE. The present data indicate that AE could prevent thyroid dysfunction and reduce its complications on the nervous system including oxidative stress and neuroinflammation.
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Corteza Cerebral/efectos de los fármacos , Hipotiroidismo , Fármacos Neuroprotectores , Extractos Vegetales , Animales , Modelos Animales de Enfermedad , Hipotiroidismo/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Masculino , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Raíces de Plantas , Ratas , Ratas WistarAsunto(s)
Antioxidantes/uso terapéutico , Curcumina/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Animales , Antioxidantes/farmacología , Curcuma/química , Curcumina/farmacología , Modelos Animales de Enfermedad , Peroxidación de Lípido , Masculino , Nanopartículas , Fármacos Neuroprotectores/farmacología , Pilocarpina , Extractos Vegetales/farmacología , Ratas Wistar , Estado Epiléptico/inducido químicamenteRESUMEN
Multiple sclerosis, an autoimmune inflammatory disease of the central nervous system, is characterized by excessive demyelination. The study aimed to investigate the possible protective effect of ozone (O3) therapy in ethidium bromide (EB)-induced demyelination in rats either alone or in combination with corticosteroids in order to decrease the dose of steroid therapy. Rats were divided into Group (1) normal control rats received saline, Group (2) Sham-operated rats received saline, Group (3) Sham-operated rats received vehicle (oxygen), Group (4) EB-treated rats received EB, Group (5) EB-treated rats received O3, Group (6) EB-treated rats received methylprednisolone (MP), and Group (7) EB-treated rats received half the dose of MP concomitant with O3. EB-treated rats showed a significant increase in the number of footfalls in the grid walk test, decreased brain GSH, and paraoxonase-1 enzyme activity, whereas brain MDA, TNF-α, IL-1ß, INF-γ, Cox-2 immunoreactivity, and p53 protein levels were increased. A significant decline in brain serotonin, dopamine, norepinephrine, and MBP immunoreactivity was also reported. Significant improvement of the above-mentioned parameters was demonstrated with the administration of either MP or O3, whereas best amelioration was achieved by combining half the dose of MP with ozone.
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Enfermedades Desmielinizantes/tratamiento farmacológico , Actividad Motora/efectos de los fármacos , Ozono/uso terapéutico , Animales , Antioxidantes/farmacología , Enfermedades Desmielinizantes/inducido químicamente , Etidio/toxicidad , Interleucina-1beta/metabolismo , Masculino , Actividad Motora/fisiología , Oxidantes Fotoquímicos/farmacología , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The present study aimed to investigate the effect of curcumin and Nigella sativa oil (NSO) on amino acid neurotransmitter alterations and the histological changes induced by pilocarpine in the hippocampus and cortex of rats. Epilepsy was induced by i.p. injection of pilocarpine, and the animals were left for 22 days to establish spontaneous recurrent seizures. They were then treated with curcumin, NSO or valproate for 21 days. Pilocarpine induced a significant increase in hippocampal aspartate and a significant decrease in glycine and taurine levels. In the cortex, a significant increase in aspartate, glutamate, GABA, glycine, and taurine levels was obtained after pilocarpine injection. Treatment of pilocarpinized rats with curcumin and valproate ameliorated most of the changes in amino acid concentrations and reduced the histopathological abnormalities induced by pilocarpine. N. sativa oil failed to improve the pilocarpine-induced abnormalities. This may explain the antiepileptic effect of curcumin and suggest its use as an anticonvulsant.
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Anticonvulsivantes , Convulsivantes , Curcumina/farmacología , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Nigella sativa/química , Pilocarpina , Aceites de Plantas/farmacología , Ácido Valproico/farmacología , Aminoácidos/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Cromatografía Líquida de Alta Presión , Compuestos de Dansilo/química , Epilepsia/patología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Neurotransmisores/metabolismo , Ratas , Ratas WistarRESUMEN
Oxidative stress has been implicated to play a role in epileptogenesis and pilocarpine-induced seizures. The present study aims to evaluate the antioxidant effects of curcumin, Nigella sativa oil (NSO) and valproate on the levels of malondialdehyde, nitric oxide, reduced glutathione and the activities of catalase, Naâº, Kâº-ATPase and acetylcholinesterase in the hippocampus of pilocarpine-treated rats. The animal model of epilepsy was induced by pilocarpine and left for 22 days to establish the chronic phase of epilepsy. These animals were then treated with curcumin, NSO or valproate for 21 days. The data revealed evidence of oxidative stress in the hippocampus of pilocarpinized rats as indicated by the increased nitric oxide levels and the decreased glutathione levels and catalase activity. Moreover, a decrease in Naâº, Kâº-ATPase activity and an increase in acetylcholinesterase activity occurred in the hippocampus after pilocarpine. Treatment with curcumin, NSO or valproate ameliorated most of the changes induced by pilocarpine and restored Naâº, Kâº-ATPase activity in the hippocampus to control levels. This study reflects the promising anticonvulsant and potent antioxidant effects of curcumin and NSO in reducing oxidative stress, excitability and the induction of seizures in epileptic animals and improving some of the adverse effects of antiepileptic drugs.
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Curcumina/uso terapéutico , Hipocampo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Aceites de Plantas/uso terapéutico , Ácido Valproico/uso terapéutico , Acetilcolinesterasa/efectos de los fármacos , Animales , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Nigella sativa , Pilocarpina , Ratas , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidoresRESUMEN
The current study was conducted to evaluate the chemoprevention effects of ginseng extract (GE) against pre-cancerous lesions in female Sprague-Dawley rats treated with aflatoxin B1 (AFB1) and fumonisin (FB). Six experimental groups treated for 12 weeks and included: the control group; the GE alone-treated group (150 mg/kg b.w); the group treated orally with AFB1 (17 microg/kg b.w) during the first 2 weeks and fed FB-contaminated diet (250 mg/kg diet) during the 6th to 8th weeks; the group treated with GE during the mycotoxin protocol and continued till week 10; the group treated with GE 2 weeks before AFB1 administration and continued till the end of FB treatment and the group treated with GE for 4 weeks after the toxin protocol stopped. The sequential mycotoxins treatment induced significant changes in serum biochemical parameters accompanied by severe histological and histochemical changes of the liver tissue. Treatment with GE during, before or after the treatment with the mycotoxins improved all biochemical parameters and histological picture of the liver. Moreover, treatment with GE after the administration of the mycotoxins was found to be more effective. It could be concluded that GE has a protective effects as pre-cancerous lesions and therapeutic effects as well.