Chlorophyllin supplementation modulates hyperglycemia-induced oxidative stress and apoptosis in liver of streptozotocin-administered mice

Abstract

Chlorophyllin is a water-soluble mixture of sodium-copper salts of chlorophyll with antioxidant and antimutagen properties. In this study, an attempt has been made to evaluate the effect of chlorophyllin on hyperglycemia-induced oxidative stress and apoptosis in liver of streptozotocin (STZ)-administered mice. In STZ-induced diabetes, two causative factors for pancreatic β-cell deaths are DNA alkylation and profound reactive oxygen species (ROS) generation. In this study, chlorophyllin treatment was found to be able to modulate oxidative stress and apoptosis in liver of diabetic mice. Diabetic mice exhibited a significant reduction of ROS, malondialdehyde (MDA), and protein carbonyl levels upon treatment with the chlorophyllin. However, antioxidant enzymes, such as copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and catalase (CAT) showed enhanced activity as well as expression in chlorophyllin-administered diabetic mice. The hepatoprotective effect of chlorophyllin was confirmed from the decreased activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The histological and ultrastructural studies revealed the ability of chlorophyllin to restore morphological and cellular alterations as observed in STZ-induced diabetic mice. The effect of chlorophyllin on apoptosis showed the downregulation of cysteine-dependent aspartate-specific protease (caspase) 3 and caspase 9, whereas upregulation of B-cell lymphoma-2 (Bcl-2) protein, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a few apoptotic cells. In conclusion, it can be stated that chlorophyllin treatment can exert hepatoprotective effect via modulating hyperglycemia-induced oxidative stress and apoptosis in STZ-administered diabetic mice. © 2018 BioFactors, 44(5):418-430, 2018.

Keywords: apoptosis; chlorophyllin; hepatocyte; hyperglycemia; oxidative stress.