RESUMEN
Blood lactate increases during incremental exercise at high-intensity workloads, and limited exercise capacity is a characteristic of obese animals. This study examined whether blood lactate changes in response to incremental exercise is disrupted in obese animals. Muscular and hepatic proteins that are critical in lactate metabolism were also investigated. Rats were randomized to either standard chow (control) or high-fat diet (HFD) groups. All animals underwent an incremental treadmill test after 14 wk of diet intervention. Blood lactate levels were measured before and after the treadmill test. Activities of mitochondrial oxidative phosphorylation and glycolysis were examined in muscle tissues. Proteins in the liver and skeletal muscles that participate in the turnover of blood lactate were determined by Western blot. Running time in the incremental treadmill test decreased in the HFD group, and blood lactate accumulated faster in these animals than in the control group. Animals with HFD had a decreased level of hepatic monocarboxylate transporter 2, the protein responsible for blood lactate uptake in the liver. Skeletal muscles of animals with HFD showed greater glycolytic activity and decreased content of lactate dehydrogenase B, which converts lactate to pyruvate. We conclude that blood lactate accumulated faster during incremental exercise in obese animals and was associated with their decreased exercise performance. Changes in the metabolic pattern of muscles and changes of liver and muscle proteins associated with lactate utilization likely contribute to the abnormal response of blood lactate to incremental exercise in obese animals.
Asunto(s)
Dieta Alta en Grasa , Metabolismo Energético , Ácido Láctico/sangre , Hígado/metabolismo , Contracción Muscular , Músculo Esquelético/metabolismo , Obesidad/sangre , Esfuerzo Físico , Adaptación Fisiológica , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Isoenzimas/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Masculino , Transportadores de Ácidos Monocarboxílicos/metabolismo , Músculo Esquelético/fisiopatología , Obesidad/etiología , Obesidad/fisiopatología , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
We have recently designed and synthesized several novel iminoquinone anticancer agents that have entered preclinical development for the treatment of human cancers. Herein we developed and validated a quantitative HPLC-MS/MS analytical method for one of the lead novel anticancer makaluvamine analog, TCBA-TPQ, and conducted a pharmacokinetic study in laboratory rats. Our results indicated that the HPLC-MS/MS method was precise, accurate, and specific. Using this method, we carried out in vitro and in vivo evaluations of the pharmacological properties of TCBA-TPQ and plasma pharmacokinetics in rats. Our results provide a basis for future preclinical and clinical development of this promising anticancer marine analog.
Asunto(s)
Antineoplásicos/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Pirroles/farmacocinética , Quinolonas/farmacocinética , Espectrometría de Masas en Tándem/métodos , Animales , Antineoplásicos/sangre , Pirroles/sangre , Quinolonas/sangre , Ratas Sprague-DawleyRESUMEN
1. Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats. 2. Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks. 3. Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail-flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end-products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na(+)/K(+)-ATPase in the nerves and erythrocytes. 4. Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ-diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Diabetes Mellitus Experimental/patología , Neuropatías Diabéticas/prevención & control , Indazoles/uso terapéutico , Aldehído Reductasa/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Glucemia/metabolismo , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Glutatión Peroxidasa/metabolismo , Hemoglobina Glucada/metabolismo , Productos Finales de Glicación Avanzada/sangre , Insulina/sangre , Masculino , Vaina de Mielina/patología , Dolor/prevención & control , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Nervio Sural/patologíaRESUMEN
The pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline extracted from Uncaria rhynchophylla Miq Jacks were reviewed. The alkaloids mainly act on cardiovascular system and central nervous system including the hypotension, brachycardia, antiarrhythmia, and protection of cerebral ischemia and sedation. The active mechanisms were related to blocking of calcium channel, opening of potassium channel, and regulating of nerve transmitters transport and metabolism, etc.