Abstract
The present study aimed to investigate the beneficial effects of the treatment with extracts from the edible mushroom Lactarius deterrimus (Ld) and the chestnut Castanea sativa (Cs), separately and in combination (MIX Ld/Cs), on oxidative stress and advanced glycation end-product (AGE)-mediated hepatorenal injury in a rat model of streptozotocin (STZ)-induced diabetes by examining pathways responsible for maintenance of redox homeostasis. An experimental model of diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. The examined extracts were applied separately at a dose of 60 mg/kg i.p. and in combination (60 mg/kg each extract; i.p.) for 4 weeks, starting from the last day of STZ administration. The improvement of hepatorenal function in diabetic rats treated with the extracts was associated with an improved glycemic and lipid status and suppression of oxidative stress and thereby oxidative damage of lipids and DNA. Besides the fact that both extracts inhibited protein glycation and AGE formation in vitro, they also reduced non-enzymatic glycosylation in diabetic rats in vivo. The observed antiglycation activity of the examined extracts (separately and in combination) was accompanied with the inhibition of CML-mediated RAGE/NF-κB activation and reduction of enzymatic O-GlcNAcylation in liver and kidney tissues of diabetic rats. Taken together, these results reveal that the administration of chestnut and mushroom extracts, either individually or together, activates a coordinated cytoprotective response against diabetes-induced hepatorenal injury not only through recovery of the antioxidant defense system of the cell, but also through a marked antiglycation activity.
Highlights
Diabetes mellitus (DM) type 1 is a metabolic disorder characterized by a severe deficiency in insulin secretion resulting from atrophy of the islets of Langerhans and causing hyperglycemia that results from a disruption of insulinsignaling because of insufficient insulin secretion
While the treatment of diabetic rats with the Lactarius deterrimus (Ld) extract improved the enzymatic activity of AST, the level of ALT activity and blood urea nitrogen (BUN) concentration remained elevated
Together with increased plasma cholesterol and triglyceride concentrations in STZ-induced diabetic rats, causes the generation of reactive oxygen species (ROS) which leads to cumulative oxidative damage of tissues and organs, producing long-term diabetic complications considered to be the major causes of morbidity and mortality in human diabetic populations (Lyra et al, 2006)
Summary
Diabetes mellitus (DM) type 1 is a metabolic disorder characterized by a severe deficiency in insulin secretion resulting from atrophy of the islets of Langerhans and causing hyperglycemia that results from a disruption of insulinsignaling because of insufficient insulin secretion. Perturbed insulin-signaling, elevated levels of blood glucose and increased oxidant levels arising from different sources, stimulate pathways that under physiological conditions are either not expressed or are expressed at considerably lower levels These include stimulation of polyol pathway, increased formation of AGEs (advanced glycation end-products), increased expression of the receptor for AGEs (RAGE) and its activating ligands, activation of protein kinase C and overactivity of the hexosamine biosynthetic pathway (HBP) (Mohora et al, 2007). These different pathways are interrelated and in a pathological setting potentiate each other, leading to excess production of compounds that cause cellular damage by oxidizing membrane lipids, modifying intracellular proteins and their functions and inducing DNA damage. Diabetes is estimated to be the most common cause of oxidative stress-related liver disease (Rutter, 2000; Guven et al, 2006)
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