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1.
Hum Exp Toxicol ; 38(7): 753-761, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30942101

RESUMO

Coconut oil (CO) is enriched with medium chain saturated fatty acids like lauric acid (LA), capric acid and caprylic acid, which are known to have several health benefits. LA, the predominant fatty acid in CO, is reported to possess anticancer activity mediated through oxidative stress-induced apoptosis; however, there is no clear information on its cellular signalling mechanism. The present study screened the anticancer potential of various fatty acids present in CO (capric acid, caprylic acid and LA) using in silico tools such as CDOCKER in Accelrys Discovery Studio by targeting proteins like epidermal growth factor receptor (EGFR), cyclin-dependent kinase and thymidine synthase (TS). The results were further confirmed using cell culture-based studies and quantitative PCR. Among the tested compounds, LA was found to be the most active and showed a higher affinity towards EGFR and TS. Corroborating with these results, LA-induced dose-dependent cytotoxicity towards HCT-15 (human colon cancer), HepG2 (human hepatocellular carcinoma) and Raw 264.7 (murine macrophages) cells exhibiting morphological characteristics of apoptosis. Further, in HCT-15 cells exposed to LA (30 and 50 µg/mL), the expression of EGFR was found to be downregulated by 1.33- and 1.58-fold. The study thus concludes that the anticancer activity of LA may be partially mediated by the downregulation of EGFR signalling and consequent reduction in cell viability through apoptosis. Since EGFR signalling is crucial in cancer cell survival and is a prime target in drug development, the present study has pharmacological significance.


Assuntos
Óleo de Coco/farmacologia , Neoplasias do Colo/metabolismo , Receptores ErbB/metabolismo , Ácidos Graxos/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Camundongos , Simulação de Acoplamento Molecular
2.
Hum Exp Toxicol ; 36(9): 919-930, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28466662

RESUMO

Hepatosteatosis is a complex disorder, in which insulin resistance and associated dyslipidemic and inflammatory conditions are fundamental. Dietary habit, especially regular consumption of fat and sugar-rich diet, is an important risk factor. Coconut and mustard oils (CO and MO) are medium-chain saturated and monounsaturated fats that are common dietary ingredients among the Indian populations. Present study analyzed the effect of prolonged consumption of the fresh and thermally oxidized forms of these oils on glucose tolerance and hepatosteatosis in male Wistar rats. Thermally oxidized CO (TCO) and MO (TMO) possessed higher amount of lipid peroxidation products and elevated p-anisidine values than their fresh forms. Dietary administration of TCO and TMO along with fructose altered glucose tolerance and increased hyperglycemia in rats. Dyslipidemia was evident by elevated levels of triglycerides and reduced high density lipoprotein cholesterol (HDLc) levels in fructose and edible oil-fed group ( p < 0.05). Additionally, hepatic antioxidant status was diminished and oxidative stress markers were elevated in TCO- and TMO-fed rats. Substantiating these, hike in liver function marker enzyme activities were also observed in these animals. Supporting this, histological analysis revealed higher incidence of microvesicles and hepatocellular ballooning. Results thus suggest that consumption of thermally oxidized fats may cause hepatic damage.


Assuntos
Óleo de Coco/toxicidade , Mostardeira/toxicidade , Óleos de Plantas/toxicidade , Animais , Glicemia/análise , HDL-Colesterol/sangue , Óleo de Coco/química , Dieta , Dislipidemias/etiologia , Dislipidemias/metabolismo , Dislipidemias/patologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Frutose/toxicidade , Temperatura Alta , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Mostardeira/química , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/química , Ratos Wistar , Triglicerídeos/sangue
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