RESUMEN
Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.
Asunto(s)
Animales , Masculino , Ratas , Clorofila/análogos & derivados , Fármacos Fotosensibilizantes/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucólisis/efectos de los fármacos , Hígado/fisiopatología , Fotoquimioterapia , Clorofila/administración & dosificación , Ratas Wistar , Estrés Oxidativo/fisiología , Diabetes Mellitus Experimental/patología , Quimioterapia Combinada , Metabolismo Energético/efectos de los fármacos , Glucólisis/fisiología , Hígado/patologíaRESUMEN
Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.
Asunto(s)
Clorofila/análogos & derivados , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucólisis/efectos de los fármacos , Hígado/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Fármacos Fotosensibilizantes/administración & dosificación , Animales , Clorofila/administración & dosificación , Diabetes Mellitus Experimental/patología , Quimioterapia Combinada , Metabolismo Energético/efectos de los fármacos , Glucólisis/fisiología , Hígado/patología , Masculino , Estrés Oxidativo/fisiología , Fotoquimioterapia , Ratas , Ratas WistarRESUMEN
The purpose was to determine the possible effects of exercise and/or caffeine on hypoglycemia and liver gluconeogenesis in diabetic rats. These were divided into four subgroups: (a) intraperitoneal insulin only, (b) exercise bout before insulin, (c) caffeine after insulin, and (d) exercise bout before and caffeine after insulin. The marked glycemic drop 45 min after insulin (0 min = 229.00, 45 min = 75.75) was considerably reduced (p < 0.05) by caffeine or exercise (45 min: exercise = 127.00, caffeine = 104.78). However, this systemic effect was lost (p > 0.05) when they were combined (45 min: exercise + caffeine = 65.44) (Mean, in mg·dL-1). Caffeine alone strongly inhibited liver glucose production from 2 mM lactate 45 min after insulin (without caffeine = 3.05, with caffeine = 0.27; p < 0.05), while exercise + caffeine partially re-established the liver gluconeogenic capacity (exercise + caffeine = 1.61; p < 0.05 relative to the other groups) (Mean, in µmol·g-1). The improved hypoglycemia with caffeine or exercise cannot be explained by their actions on liver gluconeogenesis. As their beneficial effect disappeared when they were combined, such association in diabetic patients should be avoided during the period of hyperinsulinemia due to the risk of severe hypoglycemia.