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Protective Effects of the Mushroom Lactarius deterrimus Extract on Systemic Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats.

Mihailović M, Arambašić Јovanović J, Uskoković A, Grdović N, Dinić S, Vidović S, Poznanović G, Mujić I, Vidaković M - J Diabetes Res (2015)

Bottom Line: In addition to a systemic antioxidant effect, the administration of the extract to diabetic rats also had a positive localized effect on pancreatic islets where it decreased AGE formation, and increased the expression of chemokine CXCL12 protein that mediates the restoration of β-cell population through the activation of the serine/threonine-specific Akt protein kinase prosurvival pathway.As a result, the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positive β-cells were increased.These results show that the ability of the L. deterrimus extract to alleviate oxidative stress and increase β-cell mass represents a therapeutic potential for diabetes management.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Institute for Biological Research, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.

ABSTRACT
The aim of this study was to assess the in vivo effects of the extract of the medicinal mushroom, Lactarius deterrimus, when administered (60 mg/kg, i.p.) daily for four weeks to streptozotocin- (STZ-) induced diabetic rats. Diabetic rats treated with the L. deterrimus extract displayed several improved biochemical parameters in the circulation: reduced hyperglycemia, lower triglyceride concentration and reduced glycated hemoglobin, glycated serum protein, and advanced glycation end product (AGE) levels. This treatment also adjusted the diabetes-induced redox imbalance. Thus, higher activities of the antioxidative enzymes, superoxide dismutase, and catalase in the circulation were accompanied by increased levels of free intracellular thiols and glutathionylated proteins after treatment with the L. deterrimus extract. In addition to a systemic antioxidant effect, the administration of the extract to diabetic rats also had a positive localized effect on pancreatic islets where it decreased AGE formation, and increased the expression of chemokine CXCL12 protein that mediates the restoration of β-cell population through the activation of the serine/threonine-specific Akt protein kinase prosurvival pathway. As a result, the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positive β-cells were increased. These results show that the ability of the L. deterrimus extract to alleviate oxidative stress and increase β-cell mass represents a therapeutic potential for diabetes management.

No MeSH data available.


Related in: MedlinePlus

The effect of L. deterrimus administration on AGE in the circulation (a) and presence of CML-modified proteins in pancreatic islets (b). Fluorescent products of AGE in the serum (a). Light photomicrographs of immunohistochemical staining for CML and RAGE of pancreatic sections within the islet (b) (magnification 40x). NDM: control rats; NDM + Ld: control rats treated daily with L. deterrimus extract for four weeks; DM: STZ-induced diabetic rats, DM + Ld: STZ-induced diabetic rats treated with L. deterrimus extract for four weeks. The values are presented as the mean ± S.E.M.; values not sharing a common superscript letter differ significantly at P < 0.05.
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fig4: The effect of L. deterrimus administration on AGE in the circulation (a) and presence of CML-modified proteins in pancreatic islets (b). Fluorescent products of AGE in the serum (a). Light photomicrographs of immunohistochemical staining for CML and RAGE of pancreatic sections within the islet (b) (magnification 40x). NDM: control rats; NDM + Ld: control rats treated daily with L. deterrimus extract for four weeks; DM: STZ-induced diabetic rats, DM + Ld: STZ-induced diabetic rats treated with L. deterrimus extract for four weeks. The values are presented as the mean ± S.E.M.; values not sharing a common superscript letter differ significantly at P < 0.05.

Mentions: Chronic hyperglycemia causes tissue damage that is mediated in part by the nonenzymatic glycation and oxidation of proteins and lipids and the formation of AGE of which CML is one of the most often used markers [29]. AGE exert their effects through interactions with their receptor RAGE that is normally expressed at low levels on the surface of most cell types. In addition to the circulation, AGE accumulate in tissues where they contribute to the development of diabetic complications. In the pancreas they play a part in progressive β-cell loss [30]. Determination of the fluorescent products of AGE in the serum revealed a 1.5-fold increase in AGE in diabetic rats. In diabetic rats administered Ld, the increase in AGE was at the control level (Figure 4(a)). Immunohistochemical staining revealed an extensive distribution of CML-positive cells in the islets of diabetic rats. In Ld-treated diabetic rats, the CML-positive cells were more disperse (Figure 4(b), CML). RAGE was observed only in the islets of diabetic rats (Figure 4(b), RAGE).


Protective Effects of the Mushroom Lactarius deterrimus Extract on Systemic Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats.

Mihailović M, Arambašić Јovanović J, Uskoković A, Grdović N, Dinić S, Vidović S, Poznanović G, Mujić I, Vidaković M - J Diabetes Res (2015)

The effect of L. deterrimus administration on AGE in the circulation (a) and presence of CML-modified proteins in pancreatic islets (b). Fluorescent products of AGE in the serum (a). Light photomicrographs of immunohistochemical staining for CML and RAGE of pancreatic sections within the islet (b) (magnification 40x). NDM: control rats; NDM + Ld: control rats treated daily with L. deterrimus extract for four weeks; DM: STZ-induced diabetic rats, DM + Ld: STZ-induced diabetic rats treated with L. deterrimus extract for four weeks. The values are presented as the mean ± S.E.M.; values not sharing a common superscript letter differ significantly at P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4499631&req=5

fig4: The effect of L. deterrimus administration on AGE in the circulation (a) and presence of CML-modified proteins in pancreatic islets (b). Fluorescent products of AGE in the serum (a). Light photomicrographs of immunohistochemical staining for CML and RAGE of pancreatic sections within the islet (b) (magnification 40x). NDM: control rats; NDM + Ld: control rats treated daily with L. deterrimus extract for four weeks; DM: STZ-induced diabetic rats, DM + Ld: STZ-induced diabetic rats treated with L. deterrimus extract for four weeks. The values are presented as the mean ± S.E.M.; values not sharing a common superscript letter differ significantly at P < 0.05.
Mentions: Chronic hyperglycemia causes tissue damage that is mediated in part by the nonenzymatic glycation and oxidation of proteins and lipids and the formation of AGE of which CML is one of the most often used markers [29]. AGE exert their effects through interactions with their receptor RAGE that is normally expressed at low levels on the surface of most cell types. In addition to the circulation, AGE accumulate in tissues where they contribute to the development of diabetic complications. In the pancreas they play a part in progressive β-cell loss [30]. Determination of the fluorescent products of AGE in the serum revealed a 1.5-fold increase in AGE in diabetic rats. In diabetic rats administered Ld, the increase in AGE was at the control level (Figure 4(a)). Immunohistochemical staining revealed an extensive distribution of CML-positive cells in the islets of diabetic rats. In Ld-treated diabetic rats, the CML-positive cells were more disperse (Figure 4(b), CML). RAGE was observed only in the islets of diabetic rats (Figure 4(b), RAGE).

Bottom Line: In addition to a systemic antioxidant effect, the administration of the extract to diabetic rats also had a positive localized effect on pancreatic islets where it decreased AGE formation, and increased the expression of chemokine CXCL12 protein that mediates the restoration of β-cell population through the activation of the serine/threonine-specific Akt protein kinase prosurvival pathway.As a result, the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positive β-cells were increased.These results show that the ability of the L. deterrimus extract to alleviate oxidative stress and increase β-cell mass represents a therapeutic potential for diabetes management.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Institute for Biological Research, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.

ABSTRACT
The aim of this study was to assess the in vivo effects of the extract of the medicinal mushroom, Lactarius deterrimus, when administered (60 mg/kg, i.p.) daily for four weeks to streptozotocin- (STZ-) induced diabetic rats. Diabetic rats treated with the L. deterrimus extract displayed several improved biochemical parameters in the circulation: reduced hyperglycemia, lower triglyceride concentration and reduced glycated hemoglobin, glycated serum protein, and advanced glycation end product (AGE) levels. This treatment also adjusted the diabetes-induced redox imbalance. Thus, higher activities of the antioxidative enzymes, superoxide dismutase, and catalase in the circulation were accompanied by increased levels of free intracellular thiols and glutathionylated proteins after treatment with the L. deterrimus extract. In addition to a systemic antioxidant effect, the administration of the extract to diabetic rats also had a positive localized effect on pancreatic islets where it decreased AGE formation, and increased the expression of chemokine CXCL12 protein that mediates the restoration of β-cell population through the activation of the serine/threonine-specific Akt protein kinase prosurvival pathway. As a result, the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positive β-cells were increased. These results show that the ability of the L. deterrimus extract to alleviate oxidative stress and increase β-cell mass represents a therapeutic potential for diabetes management.

No MeSH data available.


Related in: MedlinePlus