Evaluation of the Antioxidant and Antiglycation Effects of Lactarius deterrimus and Castanea sativa Extracts on Hepatorenal Injury in Streptozotocin-Induced Diabetic Rats

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.

Dietary Supplementation with Chestnut (Castanea sativa) Reduces Abdominal Adiposity in FVB/n Mice: A Preliminary Study

“…There were also no significant changes concerning hepatic transaminases, ALT, and AST, suggesting that dietary supplementation with chestnut did not induce hepatotoxicity at the biochemical level. This is in line with the results of Jovanović et al [25], who administered spiny burrs extracts of sweet chestnut to Wistar rats and did not observe hepatic toxicity. The results from histological and oxidative stress analyses performed in hepatic tissues agree with the blood biochemistry, indicating that the edible chestnut supplementation was safe in these experimental conditions.…”

“…A previous study in Zucker fa/fa rats (obesity rat model)concluded that omega-3 PUFAs led to a reduction in cholesterol levels [34]. Another study also found that chestnut spiny burrs extracts decreased cholesterol levels in diabetic Wistar rats [25].…”

“…A study from Nyengaard and colleagues concluded that kidney weight is positively correlated with the number of glomeruli present and the size of the glomeruli [27]. Jovanović found that diabetic Wistar rats presented a distorted renal architecture with glomerulopathy and tubular degenerescence and that treatment with sweet chestnut extract partially preserved the renal architecture [25]. In line with these observations, in the present study, we did not observe significant histological or oxidative stress changes associated with edible chestnut supplementation, even at the higher dosage of 1.1%.…”

Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase

“…Our findings revealed the in vitro effects of the extract on the prevention of lipid peroxidation, and on improved cell viability due to increased DNA protection from oxidative damage in STZ-induced rat pancreatic β-cell death [8]. We also showed that Cs and Ld extracts have the capacity to attenuate the complications observed in the pancreas, liver and kidney in STZ-induced diabetic rats [14,15]. Considering the positive properties of Ld and Cs extracts, we assumed that the administration of these extracts to diabetic rats would reduce hepatic oxidative stress and subsequent DNA damage that underlies liver tissue dysfunction in diabetes.…”

“…The mushroom L. deterrimus (Ld) was collected in the summer in Istria, Croatia. Cs and Ld extract preparation, their total phenolic and flavonoid contents and qualitative and quantitative analyses were performed using the HPLC/DAD method as described [9,14,15].…”