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1.
Med Gas Res ; 12(1): 18-23, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34472498

RESUMEN

Cytoreg is an ionic therapeutic agent comprising a mixture of hydrochloric, sulfuric, phosphoric, hydrofluoric, oxalic, and citric acids. In diluted form, it has demonstrated efficacy against human cancers in vitro and in vivo. Although Cytoreg is well tolerated in mice, rats, rabbits, and dogs by oral and intravenous administration, its mechanism of action is not documented. The acidic nature of Cytoreg could potentially disrupt the pH and levels of ions and dissolved gases in the blood. Here, we report the effects of the intravenous administration of Cytoreg on the arterial pH, oxygen and carbon dioxide pressures, and bicarbonate, sodium, potassium, and chloride concentrations. Our results demonstrate that Cytoreg does not disturb the normal blood pH, ion levels, or carbon dioxide content, but increases oxygen levels in rats. These data are consistent with the excellent tolerability of intravenous Cytoreg observed in rabbits, and dogs. The study was approved by the Bioethics Committee of the University of the Andes, Venezuela (CEBIOULA) (approval No. 125) on November 3, 2019.


Asunto(s)
Equilibrio Ácido-Base , Antineoplásicos , Animales , Antineoplásicos/farmacología , Bicarbonatos/farmacología , Perros , Concentración de Iones de Hidrógeno , Ratones , Conejos , Ratas , Ratas Wistar
2.
Biol Trace Elem Res ; 200(1): 247-260, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33591492

RESUMEN

This study was conducted to compare the effects of a novel form of magnesium, Mg picolinate (MgPic), to magnesium oxide (MgO) on metabolic and cognitive functions and the expression of genes associated with these functions in rats fed a high-fat diet (HFD). Forty-two Wistar rats were divided into six groups: control, MgO, MgPic, HFD, HFD + MgO, and HFD + MgPic. Mg was supplemented at 500 mg of elemental Mg/kg diet for 8 weeks. MgPic and MgO supplementation decreased visceral fat, serum glucose, insulin, leptin, TC, TG, FFA, testosterone, FSH, LH, SHBG, IGF-1, and MDA levels, but increased brain SOD, CAT, and GSH-Px activities in HFD rats. Inflammation and cognitive-related markers (presynaptic synapsin PSD95, postsynaptic PSD93, postsynaptic GluR1, and GluR2) were improved in HFD rats administered Mg, with more significant effects seen in the MgPic group. MgPic also decreased brain NF-κB but elevated brain Nrf2 levels, compared with the HFD group. The phosphorylation levels of Akt (Thr308), Akt (Ser473), PI3K try 458/199, and Ser9-GSK-3 in the brain were improved after Mg treatment in HFD rats, with more potent effects seen from MgPic supplementation. MgPic has a higher bioavailability and is more effective in improving metabolic parameters and enhancing memory than MgO. The pro-cognitive effects of MgO and MgPic could be mediated via modulation of the AMPA-type glutamate receptor and activation of the PI3K-Akt-GSK-3ß signaling pathway. These findings further support the use of MgPic in the management of metabolic and cognitive disorders.


Asunto(s)
Dieta Alta en Grasa , Magnesio , Animales , Cognición , Dieta Alta en Grasa/efectos adversos , Glucógeno Sintasa Quinasa 3 , Glucógeno Sintasa Quinasa 3 beta , Fosfatidilinositol 3-Quinasas , Ratas , Ratas Wistar , Sinapsis
3.
Biol Trace Elem Res ; 200(1): 308-317, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33634365

RESUMEN

Aluminum exposure can mediate either acute toxicity or chronic toxicity. Aluminum exerts toxic effects on the cardiovascular system, but there are few studies on its related mechanisms. In this study, we investigated the molecular mechanism of aluminum-induced oxidative damage and apoptosis in rat cardiomyocytes. Thirty-two male Wistar rats were randomly divided into four groups, including the control group (GC), low-dose group of aluminum exposure (GL), medium-dose group (GM), and high-dose group (GH), with eight rats in each group. The GL, GM, and GH groups were given 5, 10, and 20 mg/(kg·d) of AlCl3 solution by intraperitoneal injection, and the GC group received intraperitoneal injection of the same volume of normal saline (2 ml/rat/day), 5 times a week for 28 days. At the end of the experiment, the levels of aluminum, malondialdehyde (MDA), plasma lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CKMB), and alpha-hydroxybutyrate dehydrogenase (HBDH) were measured. The pathological changes of myocardium were observed by H&E staining. The apoptosis of cardiomyocytes was detected by TUNEL staining, and the expression of apoptosis-related proteins was determined by western blot. The results showed that the levels of CKMB and HBDH in the GM and GH groups were significantly higher than those in the GC group (P < 0.05). The content of aluminum in the myocardium and serum of the aluminum exposure groups was significantly higher than that of the GC group (P < 0.05). The level of MDA in the GM and GH groups was significantly higher than that in the GC group (P < 0.05). The pathological results showed that vacuolated and hypertrophied cardiomyocytes were found in aluminum exposure groups, especially in the GM and GH groups. The TUNEL staining showed that the apoptosis rate of the aluminum exposure groups was considerably higher than that of the GC group (P < 0.05). Western blot showed that the expression of Bcl-2, an anti-apoptotic protein, in cardiomyocytes of aluminum exposure groups was lower than that of the GC group (P < 0.05), while the levels of Bax and caspase-3 in the cardiomyocytes of the GM and GH groups were higher than those of the GC group (P < 0.05). The experimental results showed that aluminum could accumulate in myocardial tissues and cause damage to cardiomyocytes. It could induce oxidative stress damage by increasing the content of MDA in cardiomyocytes and trigger cardiomyocyte apoptosis by activating the pro-apoptotic proteins caspase-3 and Bax and reducing the anti-apoptotic protein Bcl-2.


Asunto(s)
Aluminio , Miocitos Cardíacos , Aluminio/metabolismo , Aluminio/toxicidad , Animales , Apoptosis , Masculino , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Ratas , Ratas Wistar
4.
Wiad Lek ; 74(9 cz 1): 2105-2108, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34725284

RESUMEN

OBJECTIVE: The aim: To analyze and compare the features of changes in the motor activity of rats on the background of pharmacological models of depressive disorders. PATIENTS AND METHODS: Materials and methods: Depressive-like state was simulated on 40 mature male Wistar rats using: reserpine (15 mg/kg), clonidine (0.1 mg/kg), haloperidol (0.25 mg/kg). The control group was given as a single dose 0.5 ml of a 0.9% sodium chloride solution intraperitoneally. After 3, 12, 24, 48 and 72 hours from the beginning of the experiment, changes in motor activity in the "open field" test were examined by the number of crossed squares, the calculation was carried out within 5 minutes. RESULTS: Results: Reserpine at a dose of 15 mg/kg caused probable motor activity disorders in rats in the "open field" test during all study periods. The most pronounced inhibition of motor activity was observed within 12-48 hours from the beginning of the experiment. 3 hours after clonidine administration, the number of crossed squares decreased by 310% (p<0.001), after 12 hours - by 180% (p<0.001), after 24 hours - by 140% (p<0.001), after 48 hours - by 50% (p<0.005) in comparison with the control group. On 3rd day, the motor activity of rats was almost completely restored. The use of haloperidol after 3 hours most significantly impaired the motor activity of rats in the "open field" test, and its recovery was observed after 24 hours. CONCLUSION: Conclusions: Reserpine inhibited the motor activity of rats, most pronounced from 12 to 48 hours of the experiment. Clonidine inhibited mainly in the first hours of the study. Haloperidol impaired motor activity at 3rd and 12th hours of observation.


Asunto(s)
Actividad Motora , Reserpina , Animales , Clonidina/farmacología , Haloperidol/farmacología , Masculino , Ratas , Ratas Wistar , Reserpina/farmacología
5.
J Nutr Sci Vitaminol (Tokyo) ; 67(5): 292-300, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34719614

RESUMEN

Metabolic syndrome (MS) is a combination of risk factors related to the development of mainly type 2 diabetes mellitus, cardiovascular disease (CVD) and nonalcoholic fatty liver disease (NAFLD). Its prevalence has increased worldwide, and healthcare systems will face major challenges in addressing this problem. The aim of this work was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on insulin resistance (IR) and obesity associated with MS in Wistar rats. The experimental design consisted of three groups of sucrose-induced MS rats: the MS group that consumed sucrose (MS-Suc; n=5), the MS group that ingested sucrose and HBOT (MS-Suc-HBOT; n=5), the MS group that did not consume sucrose and that received HBOT (MS-HBOT; n=5) and the control group. The rats received HBOT for 20 d at 2.4 atmospheres absolute (ATA) for 60 min. Subsequently, the rats were euthanized, and body fat weight, serum biochemical parameters and microscopic analysis of adipose tissue were determined. Rats with hyperoxia had decreased body weight, adipose tissue hypertrophy, and abdominal and epididymal fat. Likewise, markers of insulin resistance (glucose, insulin and HOMA-IR), biochemical parameters of dyslipidemia (cholesterol and triglycerides) and nonalcoholic fatty liver (AST and ALT) decreased; in contrast, compared to the control group, HBOT increased the 1/HOMA-IR, HOMA-ßCell and McAuley indexes, which were related to the improvement in insulin sensitivity (p<0.05; p<0.01). HBOT showed beneficial effects in the treatment of IR and obesity associated with sucrose-induced metabolic syndrome in Wistar rats.


Asunto(s)
Diabetes Mellitus Tipo 2 , Oxigenación Hiperbárica , Resistencia a la Insulina , Síndrome Metabólico , Obesidad Abdominal , Animales , Sacarosa en la Dieta , Síndrome Metabólico/terapia , Obesidad/terapia , Obesidad Abdominal/terapia , Ratas , Ratas Wistar
6.
Braz J Biol ; 84: e250936, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34755813

RESUMEN

This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.


Asunto(s)
Quemaduras , Glutamina , Aminoácidos , Animales , Quemaduras/tratamiento farmacológico , Dipéptidos , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Wistar
7.
ACS Chem Neurosci ; 12(22): 4265-4274, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34730349

RESUMEN

Alteration of the bodily CO2 concentration and proton pump activity affects the sleep architecture. The brainstem locus coeruleus (LC) area plays an essential role in rapid eye movement (REM) sleep generation and chemoregulation. Previously, we reported that lansoprazole injections (intraperitoneal) increased REM sleep in the rats. However, it is not known if proton pumps in the LC influence REM sleep. Here, we studied the effects of lansoprazole in the LC on the neuronal activity and REM sleep expression. Male Wistar rats (250-300 g) were surgically prepared for sleep recording and drug microinjections into the LC. We determined the localization of proton pumps and expression levels of cFOS in the LC neurons immunohistochemically. Sleep-wake was recorded before and after the microinjections of drugs/vehicles. Our results demonstrate (i) the presence of proton pumps in the LC neurons, (ii) that the microinjection of lansoprazole into the LC reduced the number of cFOS+ve-TH+ve double-labeled neurons in the LC by 52.6% (p < 0.001) compared to the vehicle and (iii) that low and high doses of lansoprazole significantly increased REM sleep by 32% (p < 0.001) and 60% (p < 0.001), respectively, compared to the vehicle. Our results suggest that the proton pumps modulate the LC's noradrenergic (NE-ergic) neuronal activity and REM sleep. The increased amount of REM sleep can be attributed to the inhibition of the LC NE-ergic activity. Further, the REM sleep amount increased after the lansoprazole microinjections into the LC with a significant increase in the REM sleep episode numbers. Overall, our results suggest that proton pumps in the LC may be involved in REM sleep generation.


Asunto(s)
Locus Coeruleus , Sueño REM , Animales , Electroencefalografía , Lansoprazol/farmacología , Masculino , Microinyecciones , Neuronas , Inhibidores de la Bomba de Protones/farmacología , Ratas , Ratas Wistar , Sueño , Vigilia
8.
Pestic Biochem Physiol ; 179: 104977, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34802527

RESUMEN

Chlorpyrifos (0,0-diethyl 0-(3,5,6-trichloro-2-pyridinyl)-phosphorothioate; (CPF)) is a widely used lipophilic organophosphorus insecticide that primarily manifests into central and peripheral nervous system toxicity. However, it is poorly investigated as a developmental neurotoxicant and thus remains less explored for pharmacological interventions as well. Berberine (BBR) is a benzylisoquinoline alkaloid, primarily found in the plants of Berberidaceae family, and is used for the synthesis of several bioactive derivatives. The goal of this study was to evaluate the CPF-induced neuronal damage through lactational route and analyze the neuroprotective efficacy of berberine (BBR), a potent antioxidant compound in the F1 generation. The environmentally relevant dose of CPF (3 mg/kg b.wt.) was administered via gavage to pregnant dams from postnatal day 1 to day 20 (PND 1-20). BBR (10 mg/kg b.wt.) was administered concurrently with CPF for the same duration as a co-treatment. Levels of reactive oxygen species, lipid peroxidation, membrane bound ATPases (Na+K+ATPase, Ca2+ATPase, and Mg2+ATPase), DNA damage, histomorphological alterations, cellular apoptosis were increased, and activities of glutathione reductase, endogenous antioxidant enzymes (SOD, CAT, GST, and GR) were decreased in cerebellum and cerebrum regions of CPF exposed pups. CPF triggered neuronal apoptosis by upregulating Bax and caspase-3 and downregulating Bcl-2. Co-treatment of BBR significantly attenuated these effects of CPF signifying oxidative stress mediated chlorpyrifos induced neuronal apoptosis. Berberine treatment ameliorated the CPF-induced downregulation of Bcl-2, Bax translocation, and up-regulation of caspase-3 in F1 pups. Therefore, BBR owing to its multiple pharmacological properties can be further explored for its therapeutic potential as an alternative neuroprotective agent against lactational exposure of chlorpyrifos-induced developmental neurotoxicity.


Asunto(s)
Berberina , Cloropirifos , Insecticidas , Animales , Berberina/toxicidad , Cloropirifos/toxicidad , Insecticidas/toxicidad , Compuestos Organofosforados , Estrés Oxidativo , Ratas , Ratas Wistar
9.
Pestic Biochem Physiol ; 179: 104959, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34802538

RESUMEN

This research aimed to assess curcumin (CUR) effects on fenitrothion (FNT), a broad-spectrum organophosphate insecticide, -induced hepatorenal damage. Thirty adult male Wistar rats were allocated at random to five equal groups orally administered distilled water containing 1% carboxyl methylcellulose, corn oil (1 mL/rat), CUR (100 mg/kg b.wt.), FNT (5 mg/kg b.wt.), or CUR + FNT. CUR and FNT were dosed three times a week for two months. At the end of this trial, blood and tissue samples (liver and kidney) were subjected to molecular, biochemical, and histopathological assessments. The results revealed that CUR significantly diminished the FNT-induced up-regulation of hepatic CYP1A1 and CYP1A2 transcriptional levels. Moreover, CUR significantly suppressed the increment of the serum levels of hepatic alanine aminotransferase, gamma-glutamyl transferase, and kidney damage indicators (urea and creatinine) in FNT-intoxicated rats. Furthermore, in the hepatic and renal tissues, CUR remarkably restored the FNT-associated depletion of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione S transferase, catalase, and superoxide dismutase). In addition, CUR notably reduced the FNT-induced increment in malondialdehyde content in the hepatic and renal tissues. Besides, the pathological aberrations in liver and kidney tissues resulting from FNT exposure were significantly abolished in FNT + CUR treated rats. Overall, CUR could be an effective ameliorative agent against negative pesticide impacts like FNT.


Asunto(s)
Curcumina , Fenitrotión , Animales , Antioxidantes/metabolismo , Curcumina/farmacología , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Fenitrotión/toxicidad , Hígado/metabolismo , Estrés Oxidativo , Ratas , Ratas Wistar
10.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 39(10): 726-732, 2021 Oct 20.
Artículo en Chino | MEDLINE | ID: mdl-34727651

RESUMEN

Objective: To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats. Methods: In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-ß1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1ß) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results: Compared with the negative control group, SiO2 model group had a significant decrease in the body weight of rats (P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α, IL-1ß were all significantly increased (P<0.05) . Compared with the SiO2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly (P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α and IL-1ß were significantly decreased (P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased (P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased (P<0.05) . Conclusion: Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.


Asunto(s)
Metformina , Neumonía , Fibrosis Pulmonar , Animales , Pulmón , Masculino , Metformina/farmacología , Metformina/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Ratas , Ratas Wistar , Dióxido de Silicio , Factor de Crecimiento Transformador beta1
11.
Invest Ophthalmol Vis Sci ; 62(14): 5, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34730792

RESUMEN

Purpose: The arrangement of lens cells is regulated by ocular growth factors. Although the effects of these inductive molecules on lens cell behavior (proliferation, survival, and fiber differentiation) are well-characterized, the precise mechanisms underlying the regulation of growth factor-mediated signaling in lens remains elusive. Increasing evidence highlights the importance of heparan sulfate proteoglycans (HSPGs) for the signaling regulation of growth factors; however, the identity of the different lens HSPGs and the specific roles they play in lens biology are still unknown. Methods: Semiquantitative real-time (RT)-PCR and immunolabeling were used to characterize the spatial distribution of all known HSPG core proteins and their associated glycosaminoglycans (heparan and chondroitin sulfate) in the postnatal rat lens. Fibroblast growth factor (FGF)-2-treated lens epithelial explants, cultured in the presence of Surfen (an inhibitor of heparan sulfate [HS]-growth factor binding interactions) were used to investigate the requirement for HS in FGF-2-induced proliferation, fiber differentiation, and ERK1/2-signaling. Results: The lens expresses all HSPGs. These HSPGs are differentially localized to distinct functional regions of the lens. In vitro, inhibition of HS-sulfation with Surfen blocked FGF-2-mediated ERK1/2-signaling associated with lens epithelial cell proliferation and fiber differentiation, highlighting that these cellular processes are dependent on HS. Conclusions: These findings support a requirement for HSPGs in FGF-2 driven lens cell proliferation and fiber differentiation. The identification of specific HSPG core proteins in key functional lens regions, and the divergent expression patterns of closely related HSPGs, suggests that different HSPGs may differentially regulate growth factor signaling networks leading to specific biological events involved in lens growth and maintenance.


Asunto(s)
Regulación de la Expresión Génica/fisiología , Proteoglicanos de Heparán Sulfato/genética , Cristalino/metabolismo , Animales , Animales Recién Nacidos , Western Blotting , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Sulfatos de Condroitina/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Proteoglicanos de Heparán Sulfato/metabolismo , Heparitina Sulfato/antagonistas & inhibidores , Heparitina Sulfato/metabolismo , Cristalino/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Técnicas de Cultivo de Órganos , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Urea/análogos & derivados , Urea/farmacología
12.
Phytomedicine ; 93: 153792, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34735906

RESUMEN

BACKGROUND: Kai Xin San (KXS) was widely applied for the treatment of depression for thousands of years. However, the underlying antidepressant mechanism of KXS remains not clear. PURPOSE: This study aimed to investigate whether NLRP3 inflammasome and autophagy are involved in inflammation-induced depression and antidepressant mechanism of KXS. METHODS: Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and KXS (3, 5, and 10 g/kg/d) was administrated during the last 2 weeks of CUMS procedure. The effects of KXS on depressive-like behaviors, neuroinflammation, NLRP3 inflammasome activation, and autophagy were investigated in CUMS rats. Rat astrocytes were employed to further explore the potential mechanism of KXS in regulating NLRP3 inflammasome and autophagy. Autophagy inhibitor 3-methyladenine (3-MA, 5 mM) was used in vitro to elucidate the role of autophagy in the antidepressant mechanism of KXS. RESULTS: In vivo, KXS improved depressive-like behaviors of CUMS rats in sucrose preference test, open field test and forced swimming test. Moreover, KXS inhibited the neuroinflammation induced by CUMS and promoted autophagy in prefrontal cortex of rats. The results in vitro further validated the anti-inflammatory and proautohapgic effects of KXS. More importantly, autophagy inhibitor 3-MA diminished the inhibitory effect of KXS on NLRP3 inflammasome activation in rat astrocytes. CONCLUSION: KXS ameliorated CUMS-induced depressive behaviors in rats and inhibited the NLRP3 inflammasome-mediated inflammation in vivo and in vitro. These effects might be regulated by KXS-induced autophagy.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Antidepresivos/farmacología , Autofagia , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ratas , Ratas Wistar , Estrés Psicológico
13.
Artículo en Inglés | MEDLINE | ID: mdl-34769555

RESUMEN

Landfill leachate is a complex mixture of organic and inorganic molecules, as well as environmental pollutants that can cause harm to ecosystems and living beings. The micronucleus test in peripheral blood erythrocytes was used to evaluate the genotoxic and cytotoxic effects of exposure to a landfill leachate from an outdoor solid waste storage system on Wistar strain rats at different developmental stages, pre-adolescents and young adults, and the heavy metal content of the leachate was determined by atomic absorption spectrometry. Contents of arsenic, cadmium, chromium, mercury, and lead in the landfill leachate were outside the allowable international standards, and the exposure to the landfill leachate caused genotoxic and cytotoxic effects on Wistar rats, where the pre-adolescent animals were more susceptible to the toxics contained in the landfill leachate than young adults. Heavy metals contained in landfill leachate, individually or synergically with other molecules can be responsible for clastogenic and cytotoxic effects that can be harmful to humans and ecosystems.


Asunto(s)
Eliminación de Residuos , Contaminantes Químicos del Agua , Animales , Daño del ADN , Ecosistema , Ratas , Ratas Wistar , Residuos Sólidos/análisis , Instalaciones de Eliminación de Residuos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
14.
Einstein (Sao Paulo) ; 19: eAO6417, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-34787292

RESUMEN

OBJECTIVE: To describe electrocorticographic, electromyographic and electrocardiographic profiles to report the electrophysiological effects of caffeine in Wistar rats. METHODS: Male adult Wistar rats weighing 230g to 250g were used. Rats were allocated to one of two groups, as follows: Group 1, Control, intraperitoneal injection of 0.9% saline solution (n=27); and Group 2, treated with intraperitoneal injection of caffeine (50mg/kg; n=27). The rats were submitted to electrocorticographic, electromyographic and electrocardiographic assessment. RESULTS: Brain oscillations (delta, theta, alpha, beta and gamma) in the frequency range up to 40Hz varied after caffeine administration to rats. Powers in delta and theta oscillations ranges were preponderant. The contractile force of the skeletal striated and cardiac muscles increased. Electrocardiogram analysis revealed shorter RR, QRS and QT intervals under the effect of caffeine. CONCLUSION: In the central nervous system, there was an increase in the delta, theta and alpha amplitude spectrum, which are related to memory encoding and enhanced learning. With regard to skeletal muscle, increased contraction of the gastrocnemius muscle was demonstrated, a clear indication of how caffeine can be used to enhance performance of some physical activities. Electrocardiographic changes observed after caffeine administration are primarily related to increased heart rate and energy consumption.


Asunto(s)
Cafeína , Contracción Muscular , Animales , Cafeína/farmacología , Electrocardiografía , Masculino , Músculo Esquelético , Ratas , Ratas Wistar
15.
Acta Otorhinolaryngol Ital ; 41(5): 481-486, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34734585

RESUMEN

Objective: The aim of this study was to investigate the inhibitory effect of different doses of sodium-2-mercaptoethanesulphonate (MESNA) and 5-fluorouracil on cholesteatoma formation. Methods: Fifty-six Wistar albino male rats were divided into seven groups with eight rats in each. On the first, eighth and fifteenth days, 0.2 ml of saline was administered to the group 1 (control group), and propylene glycol to induce cholesteatoma the other groups. On the 22nd day of the study, 0.2 ml saline was given to Group 1 and Group 2. Groups 3 to 7 were treated with 0.2 ml 100% MESNA, 0.2 ml 50% MESNA, 0.2 ml 20% MESNA, 0.2 ml 5-fluorouracil and 0.1 ml 100% MESNA plus 0.1 ml 5-fluorouracil, respectively, with all applications performed by intratympanic injection. Results: Significant differences were found between Group 1 and all other groups except Group 3. Significant differences were also found between Group 3 and Groups 2, 5 and 6 (P < 0.05). Conclusions: According to the results of this study, experimental cholesteatoma induced with propylene glycol may be inhibited by MESNA at 100% concentration.


Asunto(s)
Colesteatoma del Oído Medio , Mesna , Animales , Fluorouracilo/efectos adversos , Humanos , Glicoles de Propileno , Ratas , Ratas Wistar
16.
Acta Cir Bras ; 36(9): e360903, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34755763

RESUMEN

PURPOSE: To evaluate if the perconditioning affects the antioxidant capacity in mesenteric ischemia and reperfusion injury. METHODS: Twenty-one Wistar rats were assigned into three groups, as follows: Sham, IR and rPER. The animals were subjected to mesenteric ischemia for 30 min. rPER consisted of three cycles of 5-min hindlimb ischemia followed by 5 min hindlimb perfusion at the same time to mesenteric ischemic period. After 5 minutes, blood and 5 cm of terminal ileum were harvested for thiobarbituric acid reactive substances (TBARS) and Trolox equivalent antioxidant capacity (TEAC) measurement. RESULTS: rPER technique was able to reduce intestinal tissue TBARS levels (p<0.0001), but no statistic difference was observed in blood levels between groups, although it was verified similar results in rPER and Sham group. rPER technique also enhanced TEAC levels in both blood (p = 0.0314) and intestinal tissue (p = 0.0139), compared to IR group. CONCLUSIONS: rPER appears as the most promising technique to avoid IR injury. This technique reduced TBARS levels in blood and intestinal tissue and promoted the maintenance of antioxidant defense in mesenteric acute injury.


Asunto(s)
Isquemia Mesentérica , Daño por Reperfusión , Animales , Antioxidantes , Isquemia , Ratas , Ratas Wistar , Daño por Reperfusión/prevención & control
17.
Acta Cir Bras ; 36(9): e360904, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34755764

RESUMEN

PURPOSE: The protective effect of silibinin on kidney and lung parenchyma during hepatic ischemia/reperfusion injury (IRI) is explored. METHODS: Sixty-three Wistar rats were separated into three groups: sham; control (45 min IRI); and silibinin (200 µL silibinin administration after 45 min of ischemia and before reperfusion). Immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to evaluate the expression levels of MMP2, MMP3, MMP9, and TIMP2 on kidney and lung. RESULTS: Comparing sham vs. control groups, confirmed that hepatic IRI increased both renal and lung MMP2, MMP3, MMP9 and TIMP2 expressions starting at 180 min (p<0.001). Comparison of the control vs. silibinin groups showed a statistically significant decrease in the expression levels of MMP2, MMP3, and MMP9 and increase of TIMP2 in kidney and lung parenchyma. The starting point of this decrease was at 120 min after reperfusion, both for kidney and lung parameters, and it was statistically significant at 240 min (p<0.001) for kidney, while silibinin showed a peak of lung protection at 180 min after hepatic reperfusion (p<0.001). CONCLUSIONS: Hepatic IRI causes distant kidney and lung damage, while a statistically significant protective action, both on kidney and lung parenchyma, is conveyed by the intravenous administration of silibinin.


Asunto(s)
Metaloproteinasa 2 de la Matriz , Daño por Reperfusión , Animales , Isquemia , Riñón , Pulmón , Metaloproteinasa 3 de la Matriz , Metaloproteinasa 9 de la Matriz , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Silibina
18.
Acta Cir Bras ; 36(9): e360907, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34755767

RESUMEN

PURPOSE: To assess the effects of adipocyte-derived stem cell (ASC)-injection on the survival of surgical flaps under ischemia in diabetic rats. METHODS: Diabetes was induced in 30 male Wistar rats using streptozotocin (55 mg/kg). After eight weeks, epigastric flap (EF) surgery was performed. The animals were divided into control (CG), medium-solution (MG), and ASC groups. The outcomes were: the survival area (SA), the survival/total area rate (S/TR), and expression levels (EL) of genes: C5ar1, Icam1, Nos2, Vegf-a. RESULTS: In the ASC group, compared to CG, we observed improved flap SA (CG-420 mm2 vs. ASC-720 mm2; p=0.003) was observed. The S/TR analysis was larger in the ASC group (78%) than the CG (45%). This study showed an increase in the Vegf-a EL in the ASC group (2.3) vs. CG (0.93, p=0.0008). The Nos2 EL increased four-fold in the ASC group compared to CG, and C5ar1 EL decreased almost two-fold in the ASC group vs. the CG (p=0.02). There was no difference among the groups regarding Icam1 EL. Compared to the MG, the ASC group had a bigger flap SA (720 mm2 vs. 301 mm2, respectively), a bigger S/TR (78% vs. 32%, p=0.06, respectively) and increased EL of Vegf-a (2.3 vs. 1.3, respectively). No difference between ASC-group and MG was seen regarding Nos2 (p=0.08) and C5ar1 (p=0.05). CONCLUSIONS: This study suggests that ASCs increase the survival of EF under IR in diabetic rats.


Asunto(s)
Diabetes Mellitus Experimental , Adipocitos , Tejido Adiposo , Animales , Isquemia , Masculino , Ratas , Ratas Wistar , Células Madre , Colgajos Quirúrgicos
19.
Acta Cir Bras ; 36(9): e360908, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34755768

RESUMEN

PURPOSE: To describe a new anesthetic protocol medullary and nerve roots access and in Rattus norvegicus. METHODS: Seventy female Wistar rats (n=70) were used. The animals were randomly divided into two laminectomy groups: cervical (n=40) and thoracic (n=30). In cervical group, a right posterior hemilaminectomy was performed to access the nerve roots. In thoracic group, a laminectomy of the eighth thoracic vertebra was accomplished. Thirty-five rats (20 cervical and 15 thoracic) were submitted to old anesthetic protocol (ketamine 70 mg/kg plus xylazine 10 mg/kg); and the 35 other animals (20 cervical and 15 thoracic) were submitted to a new anesthetic protocol (ketamine 60 mg/kg,xylazine 8 mg/kg and fentanyl 0.03 mg/kg). RESULTS: The time to complete induction was 4.15 ±1.20 minin ketamine, xylazine and fentanyl group, and it was 4.09 ±1.47 min in the ketamine and xylazine group. There was no correlation in the time required to perform the cervical laminectomy in the old anesthetic protocol. In all groups, the animals submitted to the old anesthetic protocol had a higher level of pain on the first and third postoperative days than the animals submitted to the new anesthetic protocol. CONCLUSIONS: The new anesthetic protocol reduces the surgical time, allows better maintenance of the anesthetic plan, and brings more satisfactory postoperative recovery.


Asunto(s)
Anestésicos , Ketamina , Animales , Femenino , Ratas , Ratas Wistar , Xilazina
20.
Pol Merkur Lekarski ; 49(293): 352-355, 2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34800022

RESUMEN

Due to the problem of treating some types of burns, it is necessary to develop new drugs. For this purpose, pharmacological studies of developed gel "Xeliogel" (based on biological material with regenerating action), which accelerates the healing of superficial burns, have been developed and previously carried out. AIM: The aim of this work was to establish the histological changes of the burn wound in the dynamics and after the experimental thermal injury and in the conditions of application of the gel "Xeliogel". MATERIALS AND METHODS: The experiments were performed on mature Wistar rats of both sexes weighing 250-260 g, randomly divided equally into four groups: 1 - group of intact animals; 2 - control pathology group; 3 - group for the treatment of which used the developed gel "Xeliogel" and 4 - group of animals with the comparison drug "Solcoseryl" (Legacy Pharmaceuticals Switzerland GmbH, Switzerland). Histological indicators of the effect of gels were recorded 3 times: on the 3rd (stage of burn shock), 7th (stage of early toxemia) and 14th (stage of late toxemia) days of the experiment. Examination of micropreparations was performed on a Nicon Eclipse CI-E microscope. Microscopy of microscopic images was performed using a Sigeta M3CMOS 14000 camcorder and Toup View software on a personal computer. RESULTS: During using the developed gel "Xeliogel" it is established that on the 3rd day of the experiment the wound surface is covered with a crust, which is formed by plasma proteins and with destroyed elements of blood. On day 7 after the experimental thermal injury, both "Xeliogel" gel and "Solcoseryl" gel were found to show that the skin defect area was also covered with a film, the main components of which were destroyed blood cells and fibrinous mass. When examining the area of the defect on the 14th day of the experiment with the use of the comparison drug "Solcoseryl" gel, wounds healing covered with an epithelial layer with a clear-layered structure was observed. CONCLUSIONS: The histological evaluation of the use of "Xeliogel" gel established that the developed gel provides healing of the wound defect on the 14th day of the experiment. There is a well-defined marginal regeneration of the epidermis, the formation of the basement membrane, the restoration of the papillary layer of the dermis and capillary system.


Asunto(s)
Quemaduras , Animales , Quemaduras/tratamiento farmacológico , Femenino , Geles , Masculino , Ratas , Ratas Wistar , Regeneración , Cicatrización de Heridas
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