Significance of urinary glycosaminoglycans/proteoglycans in the evaluation of type 1 and type 2 diabetes complications

Lepedda, Antonio Junior; Muro, Pierina De; Capobianco, Giampiero; Formato, Marilena

doi:10.1016/j.jdiacomp.2016.10.013

Cited by 25 publications

(22 citation statements)

References 96 publications

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“…Blood urea and creatinine levels, are routinely used as markers of renal functions, and are sensitive markers of renal damage (Olubunmi and Adeyemi, 2015). An increase in urea and creatinine concentration in all groups that received intraperitoneal administration of alloxan was observed in the current research when compared to control group indicating diabetic nephropathy, one of the most common complications due to diabetes (Donnelly et al, 2000;Lepedda et al, 2016). The increased levels of urea and creatinine observed could be as a result of impaired function of the kidney following damage caused by alloxan.…”

Section: Discussionsupporting

confidence: 59%

“…The histopathological findings corroborated that Alloxan caused kidney damage with severe necrosis of tubular cell, coagulative necrosis of glomeruli, severe fatty change and tubular necrosis in untreated Alloxan group. This could without doubt, be as a result of the generation of reactive oxygen species (ROS) that caused damage to the kidney architecture by interfering with various biochemical activities thus impairing the function of the kidney (Donnelly et al, 2000;Lepedda et al, 2016). There was however a dose dependent restoration of the architecture of alloxan induced renal histology with treatment with graded doses of ethanolic extract of cucumis sativus pulp.…”

Section: Discussionmentioning

confidence: 99%

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Ameliorative Effect of Ethanolic Extract of Cucumis Sativus (Cucumber) Pulp on Alloxan Induced Kidney Toxicity in Male Adult Wistar Rats

2019

JNSR

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Nephropathy is a common complication of diabetes, managed with both orthodox and herbal remedies. Cucumis sativus is a creeping plant belonging to the Cucurbitaceae family. Its edible fruits possess diverse pharmacological activities. This study investigated the effect of ethanolic extract of cucumis sativus pulp (EECSP) on alloxan induced renotoxicity in adult male Wistar rats. Thirty adult male Wistar rats weighing between 170-190g were purchased and acclimatized for 2 weeks and afterwards grouped into 6 groups (A-F) of 5 rats each. Group A (Control) received distilled water and rat feed ad libitum. Diabetes was induced in Groups B, C, D, and E with consequent renotoxicity using a single intraperitoneal injection of 150mg/kg of Alloxan after an overnight fast. Group C, D and E were afterwards treated with 100, 250 and 500mg/kg of ethanolic extract of cucumis sativus pulp respectively. Group F received 500mg/kg of EECSP. Extract administration was oral and once daily for 28days. At the end of the experiment, blood samples were collected via ocular puncture and sera separated for kidney function test. The animals were sacrificed and their kidneys collected, and prepared for light microscopy. Results showed that treatment with EECSP caused a dose dependent restoration of kidney architecture and renal functions when compared with untreated alloxan group that showed severe distortions in renal architecture and higher than normal serum urea and creatinine levels. Ethanolic extract of cucumis sativus pulp thus caused a dose dependent ameliorative effect on alloxan induced diabetic nephropathy in adult male Wistar rats.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Ethanolic Extract of Cucumis Sativus (Cucumber) Pulp on Alloxan Induced Kidney Toxicity in Male Adult Wistar Rats

2019

JNSR

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“…With decreasing morbidity, many drugs from natural product and synthetic chemicals have been developed as anti-diabetic agents. Early stages of diabetic nephropathy are characterized by low urinary excretion of albumin, with glomerular basement membrane functioning by charge-dependent permeability due to the presence of anionic constituents, especially heparin sulfate [HS, a type of glycosaminoglycan (GAG)] proteoglycans ( 2 ). Among inherited metabolic disorders, particularly mucopolysaccharidoses, GAG degradation pathways are disrupted due to enzyme deficiency ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Anti-Diabetic Effects of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling

et al. 2018

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Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

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Section: Discussionmentioning

confidence: 99%

“…The association between diabetes and GAG/PG excretion in urine has been extensively studied [ 48 ]. Except for a few studies that report no change or even a reduced excretion of GAGs/PGs, a plethora of papers evidence an increased excretion as a whole (in most of them only a quantitative analysis was performed) and in particular of HS in both type 1 and 2 diabetes, often in association with diabetic nephropathy [ 48 ]. In the last years, we reported an association among UTI and both type 1 and 2 diabetes [ 31 – 35 ] suggesting UTI as a promising marker for the chronic inflammation resulting from diabetic condition [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Levels of Urinary Trypsin Inhibitor and Structure of Its Chondroitin Sulphate Moiety in Type 1 and Type 2 Diabetes

Lepedda

Nieddu

Rocchiccioli

et al. 2018

Journal of Diabetes Research

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Background Diabetes mellitus is a global health problem representing the fifth leading cause of mortality and a major risk factor for cardiovascular diseases. In the last years, we reported an association among urinary trypsin inhibitor (UTI), a small proteoglycan that plays pleiotropic roles in many inflammatory processes, and both type 1 and 2 diabetes and developed a method for its direct quantitation and structural characterization. Methods Urine from 39 patients affected by type 1 diabetes, 32 patients with type 2 diabetes, and 52 controls were analysed. UTI was separated from the main glycosaminoglycans physiologically present in urine by anion exchange chromatography, treated for chondroitin sulphate (CS) chain complete depolymerisation, and analysed for both UTI content and CS structure. UTI identification was performed by nano-LC-MS/MS analysis. Results We evidenced increased UTI levels, as well as reduced sulphation of its CS moiety in association with diabetes, regardless of both age and medium-term glycaemic control. Furthermore, no association between UTI and albumin excretion rate was found. Conclusions Evidences suggest that UTI levels are not directly correlated with renal function or, otherwise, that they may increase before the onset of renal impairment in diabetes, representing a potential marker for the underlying inflammatory condition.

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Significance of urinary glycosaminoglycans/proteoglycans in the evaluation of type 1 and type 2 diabetes complications

Cited by 25 publications

References 96 publications

Ameliorative Effect of Ethanolic Extract of Cucumis Sativus (Cucumber) Pulp on Alloxan Induced Kidney Toxicity in Male Adult Wistar Rats

Ameliorative Effect of Ethanolic Extract of Cucumis Sativus (Cucumber) Pulp on Alloxan Induced Kidney Toxicity in Male Adult Wistar Rats

Anti-Diabetic Effects of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling

Levels of Urinary Trypsin Inhibitor and Structure of Its Chondroitin Sulphate Moiety in Type 1 and Type 2 Diabetes

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