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

Abstract

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.

Carotenoids and Chlorophylls as Antioxidants

“…The pioneer works on the inhibition of lipid peroxidation by copper chlorophylls were developed by Sato’s group [ 168 , 188 ]. Later, this effect was reported in numerous tissues, normally through the formation of lipid hydroperoxides [ 183 ], but also through the TBARS method: in lymphocytes in a concentration-dependent manner up to 75% [ 185 ], in kidney and heart tissues at the same level as ascorbic acid [ 189 ], and in the liver [ 190 , 191 , 192 ], brain [ 187 ], and serum [ 182 ].…”

“…Finally, the main biomarker of oxidative stress in proteins is the formation of carbonyl (CO) groups (aldehydes and ketones), especially on Pro, Arg, Lys, and Thr residues [ 197 ]. Measuring this oxidative biomarker, copper chlorophyllin has shown its ability to decrease the level of protein carbonyls in kidney and heart tissues at rates similar to those of ascorbic acid [ 190 ] in liver tissues [ 184 , 188 , 192 ]. An even more marked effect was observed when Caenorhabditis elegans consumed a pheophorbide-rich diet, reducing the carbonyl groups up to 80% in comparison with a control group [ 198 ].…”

“…Diabetic mice with oxidative stress induced by streptozotocine showed activation of detoxification pathways (CuZnSOD, MnSOD, CAT, GPx, and GR) in response to alternative and intraperitoneal doses of 50 mg/kg b.w. of copper chlorophyll for 28 days in kidney, heart [ 190 ], and liver tissues [ 192 ]. More recently, diabetic Wistar rats were in situ perfused with chlorophyll-based extract or chlorophyll a standard and subjected to light irradiance to induce oxidative stress.…”

Plant Extracts in Obesity: A Role of Gut Microbiota

“…Chlorophyll is an abundant green pigment and non-nutrient compound ubiquitously found in higher plants and other photosynthetic organisms. Chlorophyll has been widely used to prevent various chronic diseases because of its numerous pharmacological effects, such as anti-cancer, anti-inflammatory, and antioxidant properties (170)(171)(172). Recently, more and more studies have reported that chlorophyll also plays important roles in ameliorating obesity.…”

Biomineralized Biohybrid Algae for Tumor Hypoxia Modulation and Cascade Radio-Photodynamic Therapy

“…vulgaris was possible to aggregate in the tumor site and produce oxygen under the laser irradiation condition to promote the radiation responses of the tumor. − In addition, C. vulgaris contains abundant chlorophyll, a natural photosensitizer that can release reactive oxygen species (ROS) to kill the tumor cells when irradiated with laser for photodynamic therapy (PDT). − …”