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1.
Curr Issues Mol Biol ; 46(1): 327-339, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38248323

RESUMEN

Peripheral nerve injuries inflict severe consequences, necessitating innovative therapeutic strategies. This study investigates the potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in mitigating the consequences of peripheral nerve injury. The existing treatment methods for such injuries underscore the importance of ongoing translational research efforts. Thirty adult Wistar rats underwent sciatic nerve dissection and repair surgery. The nerves were surgically transected using micro scissors at a precise location located 1.5 cm proximal to the trifurcation site. The study included a control group and two experimental groups, one treated with saline (placebo group) and the other with liraglutide (experimental group) for 12 weeks. Motor function, electromyography (EMG), and biochemical and histopathological analyses were performed after 12 weeks of treatment. Electrophysiological assessments revealed that liraglutide improved the compound muscle action potential (CMAP) amplitude and motor function compared to the saline-treated group. Histological and immunohistochemical analyses demonstrated increased NGF expression, total axon number, and diameter and reduced fibrosis in the liraglutide group. Biochemical analyses illustrated liraglutide's antioxidative properties, evidenced by reduced malondialdehyde (MDA) levels. Galectin-3 levels were suppressed and GDF-11 levels were modulated by liraglutide, indicating anti-inflammatory and anti-apoptotic effects. Liraglutide is a promising therapeutic intervention for peripheral nerve injuries, promoting functional recovery and histopathological improvement. Its multifaceted positive impact, beyond glycemic control, suggests constructive effects on the acute and chronic inflammatory processes associated with peripheral neuropathy. These findings warrant further research to elucidate molecular mechanisms and facilitate clinical translation. The study contributes valuable insights to the growing understanding of GLP-1 receptor agonists' neuroprotective properties in the context of peripheral nerve injuries.

2.
Curr Issues Mol Biol ; 46(1): 923-933, 2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-38275673

RESUMEN

Due to its rising global prevalence, liver failure treatments are urgently needed. Sinomenine (SIN), an alkaloid from sinomenium acutum, is being studied for its liver-repair properties due to Acetaminophen (APAP) overdose. SIN's effect on APAP-induced hepatotoxicity in rats was examined histologically and biochemically. Three groups of 30 adult male Wistar rats were created: control, APAP-only, and APAP + SIN. Histopathological and biochemical analyses were performed on liver samples after euthanasia. SIN is significantly protected against APAP damage. Compared to APAP-only, SIN reduced cellular injury and preserved hepatocellular architecture. The APAP + SIN Group had significantly lower ALT, MDA, and GSH levels, protecting against hepatocellular damage and oxidative stress. SIN also had dose-dependent antioxidant properties. When examining critical regulatory proteins, SIN partially restored Sirtuin 1 (SIRT1) levels. While BMP-7 levels were unaffected, histopathological evidence and hepatocyte damage percentages supported SIN's liver-restorative effect. SIN protected and repaired rats' livers from APAP-induced liver injury. This study suggests that SIN may treat acute liver damage, warranting further research into its long-term effects, optimal dosage, and clinical applications. These findings aid liver-related emergency department interventions and life-saving treatments.

3.
Neurochem Res ; 49(4): 1034-1048, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38198049

RESUMEN

The COVID-19 pandemic catalyzed the swift development and distribution of mRNA vaccines, including BNT162b2, to address the disease. Concerns have arisen about the potential neurodevelopmental implications of these vaccines, especially in susceptible groups such as pregnant women and their offspring. This study aimed to investigate the gene expression of WNT, brain-derived neurotrophic factor (BDNF) levels, specific cytokines, m-TOR expression, neuropathology, and autism-related neurobehavioral outcomes in a rat model. Pregnant rats received the COVID-19 mRNA BNT162b2 vaccine during gestation. Subsequent evaluations on male and female offspring included autism-like behaviors, neuronal counts, and motor performance. Molecular techniques were applied to quantify WNT and m-TOR gene expressions, BDNF levels, and specific cytokines in brain tissue samples. The findings were then contextualized within the extant literature to identify potential mechanisms. Our findings reveal that the mRNA BNT162b2 vaccine significantly alters WNT gene expression and BDNF levels in both male and female rats, suggesting a profound impact on key neurodevelopmental pathways. Notably, male rats exhibited pronounced autism-like behaviors, characterized by a marked reduction in social interaction and repetitive patterns of behavior. Furthermore, there was a substantial decrease in neuronal counts in critical brain regions, indicating potential neurodegeneration or altered neurodevelopment. Male rats also demonstrated impaired motor performance, evidenced by reduced coordination and agility. Our research provides insights into the effects of the COVID-19 mRNA BNT162b2 vaccine on WNT gene expression, BDNF levels, and certain neurodevelopmental markers in a rat model. More extensive studies are needed to confirm these observations in humans and to explore the exact mechanisms. A comprehensive understanding of the risks and rewards of COVID-19 vaccination, especially during pregnancy, remains essential.


Asunto(s)
Trastorno Autístico , COVID-19 , Efectos Tardíos de la Exposición Prenatal , Humanos , Ratas , Animales , Embarazo , Femenino , Masculino , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastorno Autístico/inducido químicamente , Animales Recién Nacidos , Vacunas contra la COVID-19/efectos adversos , Vacuna BNT162 , Efectos Tardíos de la Exposición Prenatal/metabolismo , Vacunas de ARNm , Pandemias , COVID-19/prevención & control , Citocinas , ARN Mensajero
4.
Drug Chem Toxicol ; : 1-16, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38348650

RESUMEN

Streptozotocin (STZ) is used as a diabetes-inducing agent in experimental animal studies. However, it is known that STZ-induced diabetic animals show significant increases in oxidative stress parameters and neurodegeneration besides their blood glucose level. In this study, the acute and subacute toxic effects of STZ on the liver, sciatic nerve, and brain tissues were investigated in vivo rat model. Sprague-Dawley rats were divided into two groups; while 50 mg/kg STZ was administered ip to the STZ group, only saline was administered to the control group. After STZ administration, three units (100 U/mL) of subcutaneous insulin glargine were applied daily to prevent the formation of diabetes. At 24 h, 1,2, and 4 weeks after applications, rats from each group were sacrificed and tissues were removed under anesthesia. At the end of the study, compared to the control, a significant decrease in SOD and GST activity and an increase in lipid peroxidation were detected in the liver and sciatic tissues of rats in the STZ-treated group in the first 24h. Considering the TUNEL, NFκB, and NOS2 expressions, it was noted that while the effects of STZ on the liver were observed in the acute stage (24h), it had subacute effects on the brain. When apoptosis-related gene expression (Bcl-2, Bax, CASP3, CASP8, CASP9, TNF-α) and immunohistochemistry were evaluated, the apoptotic effect of STZ was observed mostly in sciatic nerve tissues. Within the scope of the study, it was revealed that STZ did not only show selective toxicity to pancreatic ß cells but also very toxic to other tissues and organs.

5.
Curr Issues Mol Biol ; 46(1): 1-10, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38275661

RESUMEN

Sepsis, a leading global cause of morbidity and mortality, involves multiple organ dysfunction syndromes driven by free radical-mediated processes. Uncontrolled inflammation in early sepsis stages can lead to acute lung injury (ALI). Activated leukocytes generate reactive oxygen species, contributing to sepsis development. Gallic acid, a phenolic compound, is known for its antimicrobial properties. This study aims to observe gallic acid's protective and restorative effect on the lungs in an experimental sepsis model. Male Wistar albino rats were subjected to a feces intraperitoneal injection procedure (FIP) to induce sepsis. Four groups were formed: normal control, FIP alone, FIP with saline, and FIP with gallic acid. Gallic acid was administered intraperitoneally at 20 mg/kg/day. Blood samples were collected for biochemical analysis, and computed tomography assessed lung tissue histopathologically and radiologically. Gallic acid significantly decreased malondialdehyde, IL-6, IL-1ß, TNF-α, CRP levels, oxidative stress, and inflammation indicators. Lactic acid levels decreased, suggesting improved tissue oxygenation. Histopathological examinations revealed reduced lung damage in the gallic-acid-treated group. Computed tomography confirmed lower lung density, indicating less severe inflammation. Arterial blood gas analysis demonstrated improved oxygenation in gallic-acid-treated rats. Gallic acid exhibited anti-inflammatory and antioxidant effects, reducing markers of systemic inflammation and oxidative stress. The findings support its potential to protect against ALI during sepsis. Comparable studies underline gallic acid's anti-inflammatory properties in different tissues. Early administration of gallic acid in sepsis models demonstrated protective effects against ALI, emphasizing its potential as an adjunct therapy to mitigate adverse outcomes. The study proposes gallic acid to reduce mortality rates and decrease the need for mechanical ventilation during sepsis-induced ALI.

6.
Neurochem Res ; 48(1): 188-195, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36040609

RESUMEN

Epilepsy is a prevalent and frequently devastating neurological disorder defined by recurring spontaneous seizures caused by aberrant electrical activity in the brain. Over ten million people worldwide suffer from drug-resistant epilepsy. This severe condition requires novel treatment approaches. Both oxidative and nitrosative stress are thought to have a role in the etiology of epilepsy. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that is used to treat type-2 diabetes mellitus. According to recent studies, Liraglutide also shows neuroprotective properties, improving memory retention and total hippocampus pyramidal neuronal population in mice. The purpose of this investigation was to determine the anti-seizure and anti-oxidative effects of liraglutide in a pentylenetetrazole (PTZ)-induced rat model of epilepsy. 48 rats were randomly assigned to two groups: those who had electroencephalography (EEG) recordings and those who underwent behavioral assessment. Rats received either intraperitoneal (IP) liraglutide at two different dosages (3-6 mg/kg) or a placebo, followed by pentylenetetrazole (IP). To determine if liraglutide has anti-seizure characteristics, we examined seizure activity in rats using EEG, the Racine convulsion scale (RCS), the time of first myoclonic jerk (FMJ), and MDA, SOD, TNF-α, IL-1ß and GAD-67 levels. The mean EEG spike wave percentage score was reduced from 75.8% (placebo) to 59.4% (lower-dose) and 41.5% (higher-dose). FMJ had increased from a mean of 70.6 s (placebo) to 181.2 s (lower-dose) and 205.2 s (higher-dose). RCS was reduced from a mean of 5.5 (placebo) to 2.7 (lower-dose) and 2.4 (higher-dose). Liraglutide (3 and 6 mg/kg i.p.) successfully decreased the spike percentages and RCS associated with PTZ induced epilepsy, as well as considerably decreased MDA, TNF-α, IL-1ß and elevated SOD, GAD-67 levels in rat brain. Liraglutide significantly decreased seizure activity at both dosages when compared to control, most likely due to its anti-oxidant and anti-inflammatory properties. The potential clinical role of liraglutide as an anti-seizure medication should be further explored.


Asunto(s)
Epilepsia , Mioclonía , Ratas , Ratones , Animales , Pentilenotetrazol/toxicidad , Liraglutida/farmacología , Liraglutida/uso terapéutico , Antioxidantes/efectos adversos , Factor de Necrosis Tumoral alfa , Epilepsia/tratamiento farmacológico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Mioclonía/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Superóxido Dismutasa , Anticonvulsivantes/uso terapéutico , Modelos Animales de Enfermedad
7.
Neurochem Res ; 48(6): 1971-1980, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36780043

RESUMEN

It is still an urgent need to find alternative and effective therapies to combat epileptic seizures. Tacrolimus as a potent immunosuppressant and calcineurin inhibitor is emerging as promising drug to suppress seizures. However, there are few reports applying tacrolimus to epilepsy and providing data for its antiseizure properties. In this study, we investigated the antiseizure effects of 5 and 10 mg/kg doses of tacrolimus treatment priorly to pentylenetetrazol (PTZ) induction of seizures in rats. As an experimental design, we establish two independent rat groups where we observe convulsive seizures following 70 mg/kg PTZ and sub-convulsive seizures detected by electroencephalography (EEG) following 35 mg/kg PTZ. Thereafter, we proceed with biochemical analyses of the brain including assessment of malondialdehyde level as an indicator of lipid peroxidation and detection of superoxide dismutase (SOD) enzyme activity and PGF2α. Tacrolimus pre-treatment dose-dependently resulted in lesser seizure severity according to Racine's scale, delayed start-up latency of the first myoclonic jerk and attenuated the spike percentages detected by EEG in seizure-induced rats. However, only the higher dose of tacrolimus was effective to restore lipid peroxidation. An increase in SOD activity was observed in the PTZ group, mediated by seizure activity per se, however, it was greater in the groups that received treatment with 5 and 10 mg/kg of Tacrolimus. PGF2α bursts following PTZ induction of seizures were reversed by tacrolimus pre-treatment in a dose-dependent manner as well. We report that the well-known immunosuppressant tacrolimus is a promising agent to suppress seizures. Comparative studies are necessary to determine the possible utilization of tacrolimus in clinical cases.


Asunto(s)
Epilepsia , Pentilenotetrazol , Humanos , Ratas , Animales , Pentilenotetrazol/toxicidad , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Dinoprost , Inmunosupresores/uso terapéutico , Inmunosupresores/farmacología , Tiempo de Tratamiento , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Encéfalo/metabolismo , Epilepsia/tratamiento farmacológico , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Modelos Animales de Enfermedad , Anticonvulsivantes/uso terapéutico
8.
Neurochem Res ; 48(5): 1412-1423, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36474102

RESUMEN

Epilepsy is a disease which affects between 1 and 2% of the population, and a large proportion of these people do not react to currently available anticonvulsant medications, indicating the need for further research into novel pharmacological therapies. Numerous studies have demonstrated that oxidative stress and inflammation occur during epilepsy and may contribute to its development and progression, indicating higher levels of oxidative and inflammatory parameters in experimental models and clinical patients. This research aimed to assess the impact of diclofenac sodium, a nonsteroidal anti-inflammatory medicine, on seizure and levels of oxidative stress and inflammatory biomarkers in a rat model of epilepsy triggered by pentylenetetrazole (PTZ). 60 rats were randomly allocated to one of two groups: electroencephalography (EEG) recordings or behavioral evaluation. Rats received diclofenac sodium at three various doses (25, 50, and 75 mg/kg) intraperitoneally (IP) or a placebo, followed by intraperitoneal (IP) pentylenetetrazole, a powerful seizure-inducing medication. To investigate if diclofenac sodium had antiseizure properties, seizure activity in rats was evaluated using EEG recordings, the Racine convulsion scale (RCS) behaviour score, the duration of the first myoclonic jerk (FMJ), and the levels of MDA, TNF-α, and SOD. The average percentage of EEG spike waves decreased from 76.8% (placebo) to 64.1% (25 mg/kg diclofenac), 55.9% (50 mg/kg diclofenac), and 37.8% (75 mg/kg diclofenac). FMJ had increased from a mean of 58.8 s (placebo), to 93.6 s (25 mg/kg diclofenac), 185.8 s (50 mg/kg diclofenac) and 231.7 s (75 mg/kg diclofenac). RCS scores decreased from a mean score of 5.6 (placebo), to 3.75 (25 mg/kg diclofenac), 2.8 (50 mg/kg diclofenac) and 1.75 (75 mg/kg diclofenac). MDA levels reduced from 14.2 ng/gr (placebo) to 9.6 ng/gr (25 mg/kg diclofenac), 8.4 ng/gr (50 mg/kg diclofenac) and 5.1 ng/gr (75 mg/kg diclofenac). Likely, TNF-α levels decreased from 67.9 ng/gr (placebo) to 48.1 ng/gr (25 mg/kg diclofenac), 33.5 ng/gr (50 mg/kg diclofenac) and 21.3 ng/gr (75 mg/kg diclofenac). SOD levels, however, enhanced from 0.048 U/mg (placebo) to 0.055 U/mg (25 mg/kg diclofenac), 0.14 U/mg (50 mg/kg diclofenac), and 0.18 U/mg (75 mg/kg diclofenac). Diclofenac sodium (25, 50, and 75 mg/kg i.p.) effectively lowered the spike percentages and RCS scores linked with PTZ-induced epilepsy in rats, as well as significantly decreased MDA, TNF-α, IL-1ß, PGE2 and increased SOD levels. Probably as a result of its anti-oxidative and anti-inflammatory effects, diclofenac sodium dramatically lowered seizure activity at both doses compared to placebo control. Each of these results were significant, with p-values of < 0.01, < 0.05. Therefore, the therapeutic application diclofenac sodium as a potential anticonvulsant should be investigated further.


Asunto(s)
Epilepsia , Mioclonía , Ratas , Animales , Pentilenotetrazol/toxicidad , Diclofenaco/uso terapéutico , Anticonvulsivantes/efectos adversos , Factor de Necrosis Tumoral alfa , Ratas Sprague-Dawley , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Mioclonía/tratamiento farmacológico , Superóxido Dismutasa , Modelos Animales de Enfermedad
9.
Bratisl Lek Listy ; 124(1): 64-69, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36519610

RESUMEN

Cisplatin is commonly used in the treatment of lung, genitourinary, and gastrointestinal cancers. Peripheral neuropathy is the most important side effect, leading to a decrease in the dose of cisplatin or its complete cessation in the early period. 16 rats were given cisplatin at a dose of 2.5 mg/ kg/day twice a week for 4 weeks to induce neuropathy model. The rats taking Cisplatin were divided into 2 groups. Group 1 rats (n = 8) were given 1 ml/kg/day 0.9 % NaCl intraperitoneally, and Group 2 rats were given 10 mg/kg/day Propofol intraperitoneally daily for 4 weeks. The remaining 8 rats served as the control group. At the end of the study, all animals were tested for motor functions. Blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA), tumor necrosis factor (TNF-α), glutathione (GSH), IL-6 and HSP-70 levels. Electromyography findings revealed that compound muscle action potential (CMAP) amplitude was significantly higher in the cisplatin-Propofol group than in the cisplatin-saline group. Also, cisplatin-Propofol treated group showed significantly lower TNF-α, MDA and IL-6 levels and higher GSH and HSP-70 levels than cispalatin-Saline group (p < 0.01, p < 0.001). In addition, while the CMAP latency was decreased in the propofol group, the CMAP amplitude was increased, and a significant improvement was observed in the Inclined test scores. Besides, histological examinations showed an increase in axon diameter and NGF expression with Propofol treatment. This study demonstrated that Propofol exerts protective activity against cisplatin-induced neurotoxicity by increasing endogenous antioxidants and reducing lipid peroxidation and inflammation (Tab. 3, Fig. 4, Ref. 30). Text in PDF www.elis.sk Keywords: cisplatin, neuropathy, propofol, oxidative damage, inflammation.


Asunto(s)
Enfermedades del Sistema Nervioso Periférico , Propofol , Animales , Ratas , Antioxidantes/metabolismo , Cisplatino/efectos adversos , Glutatión/metabolismo , Inflamación , Interleucina-6/metabolismo , Peroxidación de Lípido , Malondialdehído/metabolismo , Estrés Oxidativo , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Factor de Necrosis Tumoral alfa/metabolismo
10.
Turk J Med Sci ; 53(5): 1281-1292, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38813015

RESUMEN

Background/aim: The subject of this study was to investigate the utility of platelet-rich plasma (PRP) in the cryopreservation process to reduce cryodamage and increase tissue viability. Materials and methods: Twenty-one female Wistar rats were randomly allocated to three groups. In Group 1 (G1), rats were not subjected to vitrification (n = 7). Group 2 (G2) was the vitrification group in which PRP was added to the basic vitrification solution (n = 7). Group 3 (G3) was the vitrification group in which fetal bovine serum was added to the basic vitrification solution (n = 7). Warmed tissues were evaluated with histochemical (HC) and immunohistochemical (IHC) staining, the TUNEL method, immunofluorescence (IF) staining, and biochemical analyses. Results: The percentages of IHC staining, TUNEL method positivity, and IF staining were significantly higher in G2 compared to both G1 and G3 (P < 0.05). G2 ovaries exhibited a significant increase in both malondialdehyde and catalase values in comparison to G1 (P < 0.05). In HC staining, degenerations in primary and secondary follicles and in ovarian tissue were more common in the PRP-supplemented group. The calcium used in PRP activation was suspected to have increased the degeneration and prevented the possible positive effects of PRP. Conclusion: To the best of our knowledge, PRP-supplemented vitrification solution was used for the first time in the literature in this study in whole rat ovarian tissue vitrification. If PRP is to be used as a component in vitrification solution for rat ovarian tissue, the use of lower amounts of calcium or different methods in PRP activation, or the use of nonactivated PRP, should be considered from the beginning.


Asunto(s)
Criopreservación , Ovario , Plasma Rico en Plaquetas , Ratas Wistar , Vitrificación , Animales , Femenino , Criopreservación/métodos , Ratas , Ovario/efectos de los fármacos
11.
Neurochem Res ; 47(5): 1290-1298, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35064518

RESUMEN

Alzheimer's disease (AD) is by far the most common cause of cognitive impairment in older adults. Current treatments are entirely focused on the symptoms of AD. A complex etiology for AD has been proposed recently, in which AD leads in elevated levels of inflammation. We previously studied digoxin's involvement in the sporadic-AD intracerebroventricular (ICV)-streptozotocin (STZ) animal model due to its anti-inflammatory and neuroprotective characteristics. 18 adult sprague-dawley rats were split into three groups: control (n = 6), STZ + Saline (n = 6), and STZ + Digoxin (n = 6). Twelve AD-induced rats were split into two groups using stereotaxy five days after STZ injection (3 mg/kg) into both lateral ventricles: one group got digoxin (0.1 mg/kg/day, i.p.) for three weeks, while the other group received saline. Following treatment, each subject was subjected to a passive avoidance learning (PAL) test, followed by brain tissue harvesting. The levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured in the brain, and neurons were counted using Cresyl violet staining in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3) cornu ammonis (CA3). ICV-STZ significantly shortened PAL latency, increased brain TNF-α levels, decreased brain ChAT activity, and decreased hippocampus neuron number. On the other hand, digoxin significantly reduced all of these STZ-induced deleterious effects. Digoxin significantly rescued rats from memory loss caused by ICV-STZ by decreasing hippocampal cell death, neuroinflammation, and cholinergic deficiency. These findings suggest that digoxin may be beneficial in treating cognitive impairment and Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Fármacos Neuroprotectores , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Animales , Región CA1 Hipocampal , Digoxina/metabolismo , Digoxina/farmacología , Digoxina/uso terapéutico , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Aprendizaje por Laberinto , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Wistar , Estreptozocina/farmacología
12.
Drug Chem Toxicol ; 45(5): 2160-2168, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33874839

RESUMEN

AIM: Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined. DESIGN AND METHODS: In total, 18 adult sprague-dawley rats were classified into 3 groups; control (n = 6), STZ + Saline (n = 6) and STZ + Dexpanthenol (n = 6). Twelve AD-induced rats through STZ-injection (3 mg/kg) into both lateral ventricles via stereotaxy were separated into two groups five days after STZ administration: one of these groups was treated with dexpanthenol (1000 mg/kg/day, i.p.) for 3 weeks and the other with saline. A passive avoidance learning (PAL) test was used after treatment, followed by brain tissue extraction in all subjects. Brain levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured and Cresyl violet staining was used to count neurons in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3). RESULTS: It was observed that ICV-STZ significantly shortened PAL latency, increased levels of TNF-α in brain, decreased activity of ChAT in brain, and number of hippocampal neurons. However, dexpanthenol significantly reduced all of those STZ-induced harmful effects. CONCLUSION: Dexpanthenol significantly prevented the memory deficit induced by ICV-STZ through mitigating neuronal loss in hippocampus, cholinergic deficiency and neuroinflammation in rats. These findings suggest that dexpanthenol may be beneficial for treating memory impairment.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Colina O-Acetiltransferasa/metabolismo , Modelos Animales de Enfermedad , Hipocampo , Humanos , Aprendizaje por Laberinto , Trastornos de la Memoria/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Neuronas , Fármacos Neuroprotectores/farmacología , Ácido Pantoténico/análogos & derivados , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Estreptozocina/toxicidad , Factor de Necrosis Tumoral alfa/metabolismo
13.
Int J Neurosci ; 132(11): 1150-1164, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35584252

RESUMEN

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology. In this study, we aimed to determine the ameliorating effects of vardenafil in the ASD rat model induced by propionic acid (PPA) in terms of neurobehavioral changes and also support these effects with histopathological changes, brain biochemical analysis and magnetic resonance spectroscopy (MRS) findings. MATERIALS AND METHODS: Twenty-one male rats were randomly assigned into three groups. Group 1 (control, 7 rats) did not receive treatment. Rats in groups 2 and 3 were given PPA at the dose of 250 mg/kg/day intraperitoneally for 5 days. After PPA administration, animals in group 2 (PPAS, 7 rats) were given saline and animals in group 3 (PPAV, 7 rats) were given vardenafil. Behavioral tests were performed between the 20th and 24th days of the study. The rats were taken for MRS on the 25th day. At the end of the study, brain levels of interleukin-2 (IL-2), IL-17, tumor necrosis factor-α, nerve growth factor, cGMP and lactate levels were measured. In the cerebellum and the CA1 and CA3 regions of the hippocampus, counts of neurons and Purkinje cells and glial fibrillary acidic protein (associated with gliosis) were evaluated histologically. RESULTS: Three chamber sociability and passive avoiding test, histopathological results, lactate levels derived from MRS, and biochemical biomarkers revealed significant differences among the PPAV and PPAS groups. CONCLUSION: We concluded that vardenafil improves memory and social behaviors and prevent loss of neuronal and Purkinje cell through its anti-inflammatory and neuroprotective effect.


Asunto(s)
Trastorno del Espectro Autista , Fármacos Neuroprotectores , Animales , Ratas , Masculino , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/tratamiento farmacológico , Interleucina-2/efectos adversos , Proteína Ácida Fibrilar de la Glía/metabolismo , Diclorhidrato de Vardenafil/efectos adversos , Interleucina-17 , Fármacos Neuroprotectores/efectos adversos , Factor de Necrosis Tumoral alfa , Propionatos/efectos adversos , Antiinflamatorios , Factores de Crecimiento Nervioso/efectos adversos , Lactatos/efectos adversos , Modelos Animales de Enfermedad
14.
Bratisl Lek Listy ; 123(9): 648-652, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36039883

RESUMEN

Epilepsy is a widespread and mainly severe neurological condition portrayed by recurring spontaneous seizures caused by the brain's abnormal electrical activity. According to new research, inflammation may be both a result and the cause of epileptic seizures. The highest zinc levels in the brain have been found in the hippocampus which is one of the most studied regions of the brain regarding epilepsy. Zinc may have an anti-inflammatory potential as zinc co-factors affect numerous biochemical and physiological reactions. In this study, we evaluated the effects of intraperitoneal zinc administration on seizure activity in murine PTZ model. Rats received either intraperitoneal (IP) zinc sulfate at two different dosages (50-100 mg/kg) or a placebo followed by pentylenetetrazole (IP), a strong seizure-inducing drug. The spike percentages were considerably lower in the PTZ (35 mg/kg) and 50 or 100 mg/kg zinc-treated groups (A3 and A4) than in the PTZ (35 mg/kg) and saline-treated group (A2; p may be used as an adjuvant therapy in combination with other antiepileptic drugs in the future (Tab. 3, Fig. 1, Ref. 27) Keywords: anti-seizure effect of zinc, epilepsy, abnormal electrical activity, antiepileptic drugs, rat model.


Asunto(s)
Anticonvulsivantes , Epilepsia , Animales , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Modelos Animales de Enfermedad , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Hipocampo , Ratones , Pentilenotetrazol/efectos adversos , Ratas , Zinc/uso terapéutico
15.
Bratisl Lek Listy ; 123(11): 828-832, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36254641

RESUMEN

BACKGROUND: Sepsis is one of the leading causes of death in intensive care units worldwide. Vitamins C and E are natural antioxidants and anti-inflammatory agents. Suppressing the inflammation is an important treatment target because it plays a role in the pathophysiology of sepsis. The purpose of this study was to investigate the effect of vitamins C and E treatment in rats with sepsis-induced lung damage. METHODS: In this animal study, fecal intraperitoneal injection procedure (FIP) was performed on 30 of 40 rats included for creating a sepsis model. Rats were randomly assigned into four groups: Group 1, control group (no procedure was applied, n = 10), Group 2, FIP (untreated septic group n = 10), Group 3, FIP+vitC (treated with 500 mg/kg/day ascorbic acid, n = 10), and Group 4, FIP+vitE (treated with 300 mg/kg/day alpha-tocopherol, n = 10). Chest CT was performed in all rats and density of the lungs was measured by using Hounsfield unit (HU). Histopathological examination of lung damage was performed, and blood samples were collected for biochemical analysis. RESULTS: TNF-α, CRP, IL 1-ß, IL-6, and MDA plasma levels in groups treated with vitamin C or vitamin E were lower than in the FIP group. Histological scores in groups treated either with vitamin C or vitamin E were significantly lower as compared to those in the FIP group. The HU value of lung in groups treated wither with vitamin C or vitamin E were lower than that in the FIP group (p < 0.05). CONCLUSION: The rats treated either with vitamin C or E showed improved results for sepsis. We think that they can be used as adjuvant therapy for septic patients because of their effectivity and low costs (Tab. 3, Fig. 2, Ref. 27).


Asunto(s)
Ácido Ascórbico , Sepsis , Animales , Antiinflamatorios , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Interleucina-1 , Interleucina-6 , Pulmón , Ratas , Sepsis/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Factor de Necrosis Tumoral alfa , Vitamina E/farmacología , Vitamina E/uso terapéutico , Vitaminas/farmacología , Vitaminas/uso terapéutico , alfa-Tocoferol
16.
Neurochem Res ; 46(7): 1717-1724, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33811624

RESUMEN

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. So, we researched the effects of Otilonium bromide (OB), an antisposmolytic drug that inhibits TTCC, on seizure activity in rats with pentylenetetrazol (PTZ) induced convulsion. Randomly, 48 rats were divided into two groups; for electroencephalography (EEG) recordings and for behavioral assesment. Rats were treated with either intraperitoneal (IP) OB at two separate doses (25 mg/kg and 50 mg/kg) or placebo, and then pentylenetetrazole (IP), a potent seizure-inducing chemical administered to them. In our model we have measured rat seizure activity with EEG, the convulsion scala of Racine (RCS), the time of first myoclonic jerk (FMJ) and MDA levels to assess if OB has antiepileptic properties. The mean EEG spike wave percentage score reduced from 79.5% (placebo) to 59.2% (lower-dose) and 35.2% (higher-dose). FMJ had increased from a mean of 67.2 s (placebo), to 105.2 (lower-dose), 150.6 (higher-dose). RCS reduced from a mean of 5.12 (placebo) to 4.4 (lower-dose), 3.8 (higher-dose). MDA leves reduced from 84.5 nmol/gr to 51.09 nmol/gr (lower-dose), 33.2 nmol/gr (higher-dose). Compared to placebo, OB reduced significantly seizure activity at both doses, probably through blocking T-type calcium channels. All these results were statistically significant with < 0.0001 p-values. Otilonium bromide reduced seizure activity in rats with PTZ-induced convulsion. Therefore, the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs should be further investigated.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Compuestos de Amonio Cuaternario/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Electroencefalografía/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Pentilenotetrazol , Ratas Sprague-Dawley , Convulsiones/inducido químicamente , Convulsiones/metabolismo
17.
J Obstet Gynaecol Res ; 47(12): 4319-4328, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34595798

RESUMEN

AIM: To study (1) ovarian and endometrial damage caused by the hyperglycemia and (2) the effects of dichloroacetic acid (DCA) on follicular reserve and endometrial damage in streptozocin induced diabetic rats. METHODS: This study consisted 24 rats randomly separated into three groups. A diabetes model was achieved in 16 rats experimentally, and normoglycemic eight rats were assigned as control group (Group 1). The rats with diabetes were randomly separated to two groups: 1 mL/kg/day intraperitoneal 0.9% NaCl was given to eight rats as diabetic vehicle (Group 2) and 10 mg/kg/day DCA was given to other eight rats as DCA treated group (Group 3). Hysterectomy with bilateral oophorectomy was performed for histopathological evaluation and blood samples were collected after 4 weeks. RESULTS: Diabetes caused ovarian and endometrial damage (p < 0.0001). Pentraxin-3 (PTX-3), lactic acid, and transforming growth factor-beta (TGF-ß) were higher (p < 0.05, p < 0.05, and p < 0.0001, respectively), whereas anti-Mullerian hormone (AMH) was lower in diabetic rats (p < 0.05). These findings reflected the diabetic damage in the genital tract and diminished ovarian reserve occurred via fibrosis, severe inflammation, and oxidative stress. DCA improved the histopathological fibrosis and degeneration in the ovaries and endometrium (p < 0.05). There was a concominant decrease of TGF-ß and lactic acid levels with DCA treatment (p < 0.05). DCA also improved ovarian reserve with higher AMH levels (p < 0.05). CONCLUSIONS: The several unfavored changes in the endometrium and ovaries due to diabetes have been determined in this present study. DCA might provide the continuity of the endometrial cycle, physiological endometrial structure, ovarian follicular growth, oocyte maturation, and physiological ovarian function by decreasing the lactate levels via inhibiting pyruvate dehydrogenase kinase enzyme.


Asunto(s)
Diabetes Mellitus Experimental , Reserva Ovárica , Animales , Hormona Antimülleriana , Ácido Dicloroacético , Endometrio , Femenino , Ratas
18.
Arch Gynecol Obstet ; 303(4): 1099-1108, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33140116

RESUMEN

PURPOSE: Ovarian hyperstimulation syndrome (OHSS) is a life-threatening complication of ovarian stimulation in reproductive medicine. Here, we aimed to investigate the role of oxytocin (OT) and cabergoline in the prevention and alleviation of the OHSS in an animal model. METHODS: Thirty-five female immature Wistar rats were randomly assigned to five groups. The control group (n = 7) received saline only for five consecutive days. Remaining twenty-eight rats received 10 IU of pregnant mare serum gonadotropin (PMSG) followed by 30 IU of human chorionic gonadotropin (hCG) to induce OHSS. Group 2 (n = 7) was managed with no additional intervention after the induction of OHSS. Group 3 (n = 7) received 100 µg/kg cabergoline 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Group 4 (n = 7) and group 5 (n = 7) received 80 µg/kg and 160 µg/kg OT after induction of OHSS, respectively. Oxytocin was administered 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Body and ovary weight, vascular permeability (VP), VEGF expression in the ovaries, and levels of VEGF in the peritoneal fluids were examined in all animals. RESULTS: Cabergoline and OT reduced body weight, ovary weight, and VP compared to that of the OHSS group (p < 0.05). VEGF expressions in ovaries and peritoneal VEGF levels were decreased in cabergoline and OT groups compared to that of the OHSS groups (p < 0.001 for cabergoline and OT-80 µg/kg; p < 0.00001 for OT-160 µg/kg). However, there was no statistically significant difference in these parameters between the OT and cabergoline groups. CONCLUSION: Both OT and cabergoline were active in the alleviation of OHSS through suppression of VEGF and VP. Overall, we conclude that OT is effective for downregulation for VEGF and improvement in vascular permeability in OHSS.


Asunto(s)
Cabergolina/uso terapéutico , Síndrome de Hiperestimulación Ovárica/tratamiento farmacológico , Oxitócicos/uso terapéutico , Oxitocina/uso terapéutico , Animales , Cabergolina/administración & dosificación , Cabergolina/farmacología , Modelos Animales de Enfermedad , Femenino , Oxitócicos/administración & dosificación , Oxitócicos/farmacología , Oxitocina/administración & dosificación , Oxitocina/farmacología , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos
19.
Neurochem Res ; 45(10): 2409-2416, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32719978

RESUMEN

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used as an anti-inflammatory, anti-pyretic, and analgesic. Although some studies have focused on the anti-inflammatory and anti-pyretic properties of ibuprofen during febrile convulsions, only one has investigated its antiepileptic effects. In the present study, we aimed to investigate the effects of ibuprofen in rats exposed to pentylenetetrazol (PTZ)-induced seizures. In total, 48 rats were randomly divided in two groups: Group A for electroencephalography (EEG) recordings and Group B for behavioral assessment. All EEG recordings and behavioral assessment protocols were performed. In addition, groups were compared in terms of prostaglandin F2 alfa (PGF2α) levels in the brain. We demonstrated the beneficial effects of the administration of ibuprofen in PTZ-induced seizures in rats via the following findings: spike percentages and Racine convulsion scale values were significantly lower and first myoclonic jerk (FMJ) onset times were significantly higher in the ibuprofen-administered groups. Moreover, PGF2α levels in the brain were significantly higher in the saline and PTZ 70 mg/kg group than in the control and PTZ 70 mg/kg and 400 mg/kg ibuprofen groups. Our study is the first to demonstrate the beneficial effects of ibuprofen on seizures through behavioral, EEG, and PGF2α brain assessments. Ibuprofen can be used for epilepsy and febrile seizures safely and without inducing seizures. However, further experimental and clinical studies are needed to confirm our results.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Ibuprofeno/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Dinoprost/metabolismo , Masculino , Mioclonía/inducido químicamente , Mioclonía/tratamiento farmacológico , Pentilenotetrazol , Ratas Sprague-Dawley , Convulsiones/inducido químicamente
20.
J Biochem Mol Toxicol ; 34(1): e22415, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31682045

RESUMEN

The aim of this study was to assess the therapeutic potential of oxytocin and liraglutide (LIR), a GLP-1 analogue, in a rat model of vincristine-induced neuropathy. Rats were injected with vincristine (VCR) at a dose of 4 mg/kg twice a week for 5 weeks. The VCR-administered rats were divided into three groups and received saline, oxytocin, or liraglutide simultaneously with VCR. After the treatment period, electrophysiological, biochemical, histological, and immunohistochemical investigations were performed. Electromyography (EMG) recordings demonstrated significant alterations in the VCR + saline group (p < .001). Also, motor performance was decreased in the VCR + saline group (p < .05). Histologically, the axonal diameter was decreased in all groups. VCR + saline group showed significantly increased lipid peroxidation and decreased nerve growth factor (NGF) expression. However, the administration of oxytocin and liraglutide significantly prevented the EMG alterations, lipid peroxidation, and reduction in neuronal NGF expression. On the basis of these findings, oxytocin and liraglutide may be considered as potential agents for the prevention of VCR-induced neuropathy.


Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Liraglutida/uso terapéutico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Oxitocina/uso terapéutico , Vincristina/toxicidad , Animales , Liraglutida/administración & dosificación , Masculino , Enfermedades del Sistema Nervioso/inducido químicamente , Oxitocina/administración & dosificación , Ratas , Ratas Sprague-Dawley
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