Chlorophyll treatment combined with photostimulation increases glycolysis and decreases oxidative stress in the liver of type 1 diabetic rats

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.

Chlorophyll treatment combined with photostimulation increases glycolysis and decreases oxidative stress in the liver of type 1 diabetic rats.

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.

Pros and cons of insulin administration on liver glucose metabolism in strength-trained healthy mice.

Non-diabetic individuals use hormones like insulin to improve muscle strength and performance. However, as insulin also leads the liver and the adipose tissue to an anabolic state, the purpose of this study was to investigate the effects of insulin on liver metabolism in trained non-diabetic Swiss mice. The mice were divided into four groups: sedentary treated with saline (SS) or insulin (SI) and trained treated with saline (TS) or insulin (TI). Training was made in a vertical stair, at 90% of the maximum load, three times per week. Insulin (0.3 U/kg body weight) or saline were given intraperitoneally five times per week. After eight weeks, tissue and blood were collected and in situ liver perfusion with glycerol+lactate or alanine+glutamine (4 mM each) was carried out. The trained animals increased their muscle strength (+100%) and decreased body weight gain (-11%), subcutaneous fat (-42%), mesenteric fat (-45%), and peritoneal adipocyte size (-33%) compared with the sedentary groups. Insulin prevented the adipose effects of training (TI). The gastrocnemius muscle had greater density of muscle fibers (+60%) and less connective tissue in the trained groups. Liver glycogen was increased by insulin (SI +40% and TI +117%), as well as liver basal glucose release (TI +40%). Lactate and pyruvate release were reduced to a half by training. The greater gluconeogenesis from alanine+glutamine induced by training (TS +50%) was reversed by insulin (TI). Insulin administration had no additional effect on muscle strength and reversed some of the lipolytic and gluconeogenic effects of the resistance training. Therefore, insulin administration does not complement training in improving liver glucose metabolism.

Pros and cons of insulin administration on liver glucose metabolism in strength-trained healthy mice

Non-diabetic individuals use hormones like insulin to improve muscle strength and performance. However, as insulin also leads the liver and the adipose tissue to an anabolic state, the purpose of this study was to investigate the effects of insulin on liver metabolism in trained non-diabetic Swiss mice. The mice were divided into four groups: sedentary treated with saline (SS) or insulin (SI) and trained treated with saline (TS) or insulin (TI). Training was made in a vertical stair, at 90% of the maximum load, three times per week. Insulin (0.3 U/kg body weight) or saline were given intraperitoneally five times per week. After eight weeks, tissue and blood were collected and in situ liver perfusion with glycerol+lactate or alanine+glutamine (4 mM each) was carried out. The trained animals increased their muscle strength (+100%) and decreased body weight gain (-11%), subcutaneous fat (-42%), mesenteric fat (-45%), and peritoneal adipocyte size (-33%) compared with the sedentary groups. Insulin prevented the adipose effects of training (TI). The gastrocnemius muscle had greater density of muscle fibers (+60%) and less connective tissue in the trained groups. Liver glycogen was increased by insulin (SI +40% and TI +117%), as well as liver basal glucose release (TI +40%). Lactate and pyruvate release were reduced to a half by training. The greater gluconeogenesis from alanine+glutamine induced by training (TS +50%) was reversed by insulin (TI). Insulin administration had no additional effect on muscle strength and reversed some of the lipolytic and gluconeogenic effects of the resistance training. Therefore, insulin administration does not complement training in improving liver glucose metabolism.

Effects of nanoparticles of hydroxy-aluminum phthalocyanine on markers of liver injury and glucose metabolism in diabetic mice

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.

Effects of nanoparticles of hydroxy-aluminum phthalocyanine on markers of liver injury and glucose metabolism in diabetic mice.

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.