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1.
Toxicon ; 221: 106965, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36370827

ABSTRACT

This study investigated the antineoplastic effects of crotoxin isolated from snake venom of the South American Crotalus durissus terrificus in oral cancer cell lines and in an animal model of chemically induced oral cancer. We analyzed cell viability and death, clonogenic formation, DNA fragmentation, migration assay, and gene expression of MMP2, MMP9, COL1A1, and CASP3. In the animal model, after induction of oral cancer by 4-nitroquinoline-1-oxide carcinogen, mice were treated with crotoxin to investigate its effects on tumor development in tongue and oral mucosa. Crotoxin inhibited cell proliferation, viability, colony formation, and migration, favoring cell death. Furthermore, crotoxin increased caspase-3 expression, decreased Ki-67 protein and mRNA expression of MMP2, MMP9, and COL1A1. Mice treated with crotoxin at 10 µg/kg did not alter biochemical parameters total cholesterol, very-low-density lipoprotein, high-density lipoprotein, liver transaminases, glycemia, creatinine, and urea. Crotoxin treatment significantly reduced the frequency of oral squamous cell carcinoma lesions by 50%. Thus, this study highlights crotoxin as a promising chemotherapeutic substance, considering its effects on controlling the neoplastic cell population, reducing cell migration, and inhibiting tumor development. Clinical studies are necessary to understand better the impact of crotoxin as a potential adjuvant therapeutic agent for oral cancer patients.


Subject(s)
Antineoplastic Agents , Crotalid Venoms , Crotoxin , Mouth Neoplasms , Squamous Cell Carcinoma of Head and Neck , Animals , Mice , Antineoplastic Agents/pharmacology , Crotalid Venoms/chemistry , Crotalus , Crotoxin/pharmacology , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Mouth Neoplasms/chemically induced , Mouth Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/chemically induced , Squamous Cell Carcinoma of Head and Neck/drug therapy
2.
Arch Physiol Biochem ; 129(2): 449-459, 2023 Apr.
Article in English | MEDLINE | ID: mdl-33176505

ABSTRACT

BACKGROUND: Diet macronutrient heterogeneity hinders animal studies' data extrapolation from metabolic disorders to human diseases. OBJECTIVE: The present study aimed to evaluate different fat-diet compositions' effect on inducing lipid/glucose metabolism alterations in mice. METHODS: Swiss male mice were fed for 12 weeks with five different diets: Standard Diet (ST), American Institute of Nutrition 93 for growth (AIN93G) high-butter/high-sugar (HBHS), high-lard/high-sugar (HLHS), and high-oil/high-sugar diet (soybean oil) (HOHS). Several parameters, such as serum biochemistry, histology, and liver mRNA expression, were accessed. RESULTS: The main findings revealed that the HLHS diet dramatically altered liver metabolism inducing hepatic steatosis and increased total cholesterol, triglycerides, VLDL, increasing liver CCAAT/enhancer binding protein (CEBP-α), Acetyl-CoA carboxylase (ACC) and Catalase (CAT) mRNA expression. Moreover, the HLHS diet increased glucose intolerance and reduced insulin sensitivity. CONCLUSIONS: High-fat/high-sugar diets are efficient to induce obesity and metabolic syndrome-associated alterations, and diets enriched with lard and sugar showed more effective results.


Subject(s)
Metabolic Syndrome , Animals , Humans , Male , Mice , Diet, High-Fat , Dietary Fats/metabolism , Liver/metabolism , Metabolic Syndrome/etiology , Metabolic Syndrome/metabolism , Obesity/etiology , Obesity/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sugars/metabolism
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