RESUMEN
Alpha-lipoic acid (α-LA) is characterized by its unpleasant odor, poor bioavailability and stability. Nanotechnology was applied to overcome this limitation. So we aimed in this study to formulate α-LA in two different forms of chitosan nanoparticles (CsNPs) and solid lipid nanoparticles (SLNPs) and characterize them in terms of physical properties and biological activities against aluminum chloride (AlCl3)-induced neurotoxicity in rats. The vivo study was processed on 50 rats divided into 5 groups as follow: control, neurotoxic, treated α-LA, treated α-lipoic acid-loaded chitosan nanoparticles (α-LA-CsNPs) and treated α-lipoic acid-loaded solid lipid nanoparticles (α-LA-SLNPs) groups. The result was depicted by transmission electron microscopy (TEM) revealed that α-LA-SLNPs had a regular spherical shape while α-LA-CsNPs showed an irregular spherical form. Dynamic light scattering (DLS) analysis showed that the average particle size for α-LA-SLNPs was about 71 nm and for α-LA-CsNPs was about 126 nm. After the experimental period, we observed that AlCl3 administration significantly increased oxidative stress, neuroinflammation and apoptosis and decreased brain fatty acid contentsand brain-derived neurotrophic factor,while α-LA, α-LA-CsNPs and α-LA-SLNPs were able to ameliorate these negative changes in the neurotoxic rats. However, the effect of the α-LA-loaded NPs was more prominent than that of pristine α-LA but the α-LA-SLNPs group was almost close to the control group. Conclusion: α-LA can attenuate neurotoxicity induced by AlCl3, attributed to its anti-inflammatory, antioxidant and anti-apoptotic activities in addition to the effectiveness of the encapsulation technique that can increase the efficiency and stability of α-LA. Moreover, α-LA-SLNPs are more efficient than α-LA-CsNPs.
Asunto(s)
Quitosano , Nanopartículas , Ácido Tióctico , Animales , Liposomas , Nanopartículas/toxicidad , Ratas , Ácido Tióctico/farmacologíaRESUMEN
l-Glutaminase has gained an important attention as glutamine-depleting enzyme in treatment of various cancers. Therefore, this study aimed to purify, characterize and investigate antitumor activity of l-glutaminase from camel liver mitochondria (CL-Glu), since no available information about CL-Glu from camel. CL-Glu was purified using cell fractionation, ultrafiltration, DEAE-and CM-cellulose chromatography columns. The purified CL-Glu was a monomer with a molecular weight of 70 ± 3 kDa, isoelectric point of 7.2, optimum temperature of 70 °C and it was active over a broad pH range with a pH optimum at pH 8.0. Its activity had a clear dependence on phosphate ions. The studied enzyme showed sigmoidal kinetics, indicated its allosteric behavior with Km of 36 ± 4 mM and Hill coefficient of 1.5 which suggested a positive cooperatively of active sites. The purified l-glutaminase exerted antitumor activity against different cell lines with the highest cytotoxic activity against Hepatocellular carcinoma cell line (HepG-2) with an IC50 value of 152 µg/ml. In conclusion, l-glutaminase was purified from camel liver using simple methods and its unique properties such as stability at both wide pH range and at high temperature along with its relatively low molecular weight, facilitated its usage in medical applications as antitumor drug.
Asunto(s)
Antineoplásicos , Camelus , Carcinoma Hepatocelular/tratamiento farmacológico , Glutaminasa , Neoplasias Hepáticas/tratamiento farmacológico , Hígado/enzimología , Mitocondrias Hepáticas/enzimología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Glutaminasa/química , Glutaminasa/aislamiento & purificación , Glutaminasa/farmacología , Células HCT116 , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Células MCF-7RESUMEN
Searching for new sources of safe nutraceuticals antitumor drugs is an important issue. Consequentially, this study designed to assess the antitumor activity of Pulicaria undulata extract in vitro in the treatment of hepatocellular carcinoma HepG2 cell line. Aerial parts of P. undulata plants were collected, used for phytochemical analysis, and assessed for anticancer activity. The antitumor activity was evaluated through studying the cell viability and apoptotic pathway. The gas chromatography-mass spectrometry phytochemical analysis revealed that P. undulata is a promising new source of several known antioxidant and antitumor compounds which could participate in drug development and exploration of alternative strategies to the harmful synthetic antitumor drugs. P. undulata stifled HepG2 cell viability in a concentration-dependent manner. Meanwhile, P. undulata tempted substantial apoptosis in HepG2 cells and enhanced the expression of miR-34a. However, the mRNA expression level of antiapoptotic B-cell lymphoma-2 was markedly decreased by P. undulata treatment. Moreover, P. undulata increased the protein expression of proapoptotic p53 and caspase 3/9 with reducing B-cell lymphoma-2 protein expression level. Thus, P. undulata induced apoptosis in the HepG2 cells by overexpression of miR-34a which regulates p53/B-cell lymphoma-2/caspases signaling pathway. These findings were well appreciated with morphological studies of cells treated with P. undulata. In conclusion, P. undulata could be a probable candidate agent for the initiation of cell apoptosis in HepG2 and thereby can serve as promising therapeutic agent for treatment of hepatocellular carcinoma which should attract further studies.
Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas/patología , Extractos Vegetales/farmacología , Pulicaria/química , Carcinoma Hepatocelular/tratamiento farmacológico , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Transducción de SeñalRESUMEN
This study was designed to evaluate the possible mechanisms through which Echinops spinosus (ES) extract demonstrates nephroprotective effect on the paracetamol acetominophen (N-acetyl-p-aminophenol (APAP)) induced nephrotoxicity in rats. Twenty-four Swiss albino rats were divided into four groups (six rats each). The placebo group was orally administered sterile saline, the APAP group received APAP (200 mg·kg-1·day-1 i.p.) daily, the ES group was given ES extract orally (250 mg/kg), and the APAP + ES group received APAP as for the APAP group and administrated the ES extract as for the ES group. Pretreatment of methyl alcohol extract of ES reduced the protein expression of inflammatory parameters including cyclooxygenase-2 and nuclear factor κB in the kidney. It also reduced the mRNA gene expression of tumor necrosis factor-α and interleukin-1ß. The ES extract compensated for deficits in the total antioxidant activity, suppressed lipid peroxidation, and amended the APAP-induced histopathological kidney alterations. Moreover, ES treatment restored the elevated levels of urea nitrogen in the blood and creatinine in the serum by APAP. The ES extract attenuated the APAP-induced elevations in renal nitric oxide levels. We clarified that the ES extract has the potential to defend the kidney from APAP-induced inflammation, and the protection mechanism might be through decreasing oxidative stress and regulating the inflammatory signaling pathway through modulating key signaling inflammatory biomarkers.
Asunto(s)
Acetaminofén/efectos adversos , Echinops (Planta)/química , Enfermedades Renales/inducido químicamente , Enfermedades Renales/tratamiento farmacológico , Riñón/metabolismo , Extractos Vegetales/farmacología , Acetaminofén/farmacología , Animales , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Extractos Vegetales/química , RatasRESUMEN
BACKGROUND: Nicotine is an important factor in the pathogenesis of renal injury in smokers. PURPOSE: The purpose of the present study was to investigate the renoprotective effect of Spirulina platensis extract (SP) against chronic nicotine administration in rats. METHODS: Nicotine intoxication was induced with 0.5 mg/kg BW. Rats received 500 mg SP/kg BW by gastric gavage over 4 weeks. RESULTS: Our data revealed that nicotine induced renal dysfunction manifested by significant abnormal levels of kidney function markers (creatinine and urea) accompanied by increased levels of oxidative stress biomarker (malondialdehyde) and inflammatory markers (nitric oxide, Interleukin-6 and tumor necrosis factor-α) while antioxidant status as glutathione level and glutathione S-transferase activity were found to be decreased significantly as compared with controls. It is worthy to note that nicotine toxicity induced significant increments in the protein expression levels of nuclear factor kappa B as well as caspase-3. Histopathological observations showed tubular necrosis and congestion in the endothelial lining glomerular tuft and epithelial lining renal tubules with nicotine intoxication. Interestingly, our data demonstrated that SP supplementation significantly improved the nicotine-induced kidney dysfunction, alleviated the induced-lipid peroxidation, inflammatory, apoptotic protein markers, and boosted the enzymatic/non-enzymatic antioxidants. Moreover, it attenuated the nicotine-induced histopathological alterations of the kidney architecture. CONCLUSION: Thus, it is tempting to recommend dietary approaches with Spirulina platensis extract for smokers to minimize the deleterious effect of chronic nicotine consumption and smoke exposure-related problems towards kidney injury via the antioxidant, anti-inflammatory and antiapoptotic properties of Spirulina platensis.
Asunto(s)
Inflamación/tratamiento farmacológico , Riñón/efectos de los fármacos , Nicotina/toxicidad , Estrés Oxidativo/efectos de los fármacos , Spirulina/química , Animales , Antioxidantes/análisis , Caspasa 3/metabolismo , Creatinina/análisis , Glutatión/análisis , Glutatión Transferasa/metabolismo , Inflamación/inducido químicamente , Interleucina-6/análisis , Riñón/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/análisis , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisis , Ácido Úrico/análisisRESUMEN
Nephro-and hepatotoxicities are important complications in cancer patients undergoing cisplatin (CP) therapy. We aimed to study the protective effect of fenugreek (FG) on CP induced renal and hepatic injuries in rats. Cisplatin intoxication resulted in structural and functional renal and hepatic impairments, which were revealed by massive histopathological changes and elevated kidney and liver function tests. However, it was associated with oxidative stress and lipid peroxidation as evident by increased reactive oxygen species (ROS) and malondialdehyde (MDA) with decreased levels of total antioxidant activity. Cisplatin administration triggered inï¬ammatory responses and apoptosis in rat livers and kidneys as evident by increased expression of pro-inï¬ammatory cytokine, tumor necrosis factor- α (TNF-α) and apoptotic marker p38 mitogen-activated protein kinase (p38 MAPK) as results of overproduction of ROS. FG signiï¬cantly attenuated the cisplatin-induced biochemical and histopathological alterations, inï¬ammation and apoptosis in rat livers and kidneys. Results suggested that fenugreek co-administration has a powerful antioxidant effect and may serves as a novel and promising preventive strategy against cisplatin-induced nephron- and hepatotoxicities.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cisplatino/efectos adversos , Enfermedades Renales/tratamiento farmacológico , Extractos Vegetales/farmacología , Trigonella/química , Animales , Peso Corporal/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Etanol/química , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Pruebas de Función Renal , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/fisiopatología , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Ratas Wistar , Factor de Necrosis Tumoral alfa/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
Among various phytochemicals, coumarins comprise a very large class of plant phenolic compounds that have good nutritive value, in addition to their antioxidant effects. The purpose of the present study was to investigate the protective effects of two coumarin derivatives, umbelliferone and daphnetin, against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and elucidate the underlying mechanism. Treatment of rats with either umbelliferone or daphnetin significantly improved the CCl4-induced biochemical alterations. In addition, both compounds alleviated the induced-lipid peroxidation and boosted the antioxidant defense system. Moreover, the investigated compounds attenuated CCl4-induced histopathological alterations of the liver. Finally, umbelliferone and daphnetin induced the nuclear translocation of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective heme oxygenase-1 (HO-1). These results suggest that umbelliferone and daphnetin ameliorate oxidative stress-related hepatotoxicity via their ability to augment cellular antioxidant defenses by activating Nrf2-mediated HO-1 expression.
Asunto(s)
Antioxidantes/administración & dosificación , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Hemo-Oxigenasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Umbeliferonas/administración & dosificación , Animales , Antioxidantes/farmacología , Núcleo Celular/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Factor 2 Relacionado con NF-E2/genética , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Umbeliferonas/farmacologíaRESUMEN
Puerarin (Pur), an isoflavonoid extracted from the dried roots of Pueraria lobata, has been reported to be useful in the treatment of various diseases. This study was designed to evaluate the anti-apoptotic and anti-inflammatory activities of Pur against 3-nitropropionic acid (3-NP) induced neurotoxicity. For 5 consecutive days, male Wistar rats were given Pur (200 mg/kg body mass) 30 min before treatment with 20 mg/kg body mass of 3-NP. The striata, hippocampi, and cortices of the 3-NP treated group showed apoptotic damage, inflammation, and energy deficit as well as histopathological lesions. The 3-NP-induced alteration in apoptotic biomarkers (caspase-3 activity/level, cytosolic cytochrome c, Bax/Bcl-2 levels) were significantly ameliorated by Pur treatment. Moreover, Pur pretreatment blocked 3-NP-induced inflammatory biomarkers (NF-κB, TNF-α, and iNOS) and prevented the energy deficit (ATP reduction). Nissl staining further confirmed Pur's neuroprotective effect. These results indicate that Pur may be a useful preventive approach to various neurodegenerative diseases with underlying apoptosis and neuroinflammation.
Asunto(s)
Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Isoflavonas/farmacología , Síndromes de Neurotoxicidad/tratamiento farmacológico , Nitrocompuestos , Propionatos , Adenosina Trifosfato/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Isoflavonas/uso terapéutico , Masculino , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Ratas WistarRESUMEN
Puerarin (daidzein-8-C-glucoside), a major isoflavone glycoside purified from Pueraria lobata, is well reported to have a neuroprotective effect primarily by the antioxidant mechanisms. This investigation was designed to evaluate the efficacy of Puerarin (Pur) to offset 3-nitropropionic acid (3-NP) induced neurotoxicity. Male Wistar strain rats were given 3-NP (20 mg/kg, s.c.) over five consecutive days, whereas Pur (200 mg/kg, i.p.) was administrated 30 min before 3-NP. Rats treated with 3-NP exhibited significant weight loss, reduction of the prepulse inhibition, locomotor hypoactivity and hypothermia. The striata, hippocampi and cortices of the 3-NP treated rats showed abnormal levels of neurotransmitters, oxidative damage and characteristic histopathological lesions. Treatment with Pur ahead of 3-NP, significantly prevented weight loss, PPI deficit, locomotor hypoactivity and hypothermia. Pur treatment blocked the 3-NP-induced neurotransmitters abnormalities (GABA, DA, 5-HT and NE), and normalized the oxidative stress biomarkers (lipid peroxidation, reduced glutathione, glutathione peroxidase). Histopathological examination further affirmed Pur's neuroprotective effect against 3-NP-induced neurotoxicity. In conclusion, Pur protected the brain tissues from 3-NP induced neurotoxicity primarily by its neuromodulation and antioxidant effect.