Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats

Ghule, Arvindkumar E.; Jadhav, Suresh; Bodhankar, Subhash L.

doi:10.1016/j.intimp.2012.10.004

Cited by 67 publications

(30 citation statements)

References 40 publications

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“…Similar effects were reported for 3,5-T 2 when used as a pharmacological agent to prevent insulin resistance forced by a high-fat diet [5]. Further animal studies [27,35,36] confirmed the antidiabetic effect of both trigonelline and 3,5-T 2 , revealing protective effects on impaired kidney function and structure, which represents a severe sequelae of type 2 diabetes mellitus. Taken together, 3,5-T 2 and trigonelline were linked to glucose metabolism, exhibiting the potential to improve glucose homeostasis in the case of diminished insulin sensitivity.…”

Section: Discussionsupporting

confidence: 68%

Urine Metabolomics by 1H-NMR Spectroscopy Indicates Associations between Serum 3,5-T2 Concentrations and Intermediary Metabolism in Euthyroid Humans

et al. 2015

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Context: 3,5-Diiodo-L-thyronine (3,5-T₂) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T₂ and glucose but not lipid metabolism. Objective: The aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T₂ concentrations in healthy individuals. Study Design and Methods: Urine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by ¹H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T₂ concentrations. Results: Serum 3,5-T₂ concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T₂ concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels. Conclusion: Our findings in humans confirmed the metabolic effects of circulating 3,5-T₂ on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T₂ exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.

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Section: Discussionsupporting

confidence: 68%

Urine Metabolomics by 1H-NMR Spectroscopy Indicates Associations between Serum 3,5-T2 Concentrations and Intermediary Metabolism in Euthyroid Humans

et al. 2015

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“…Urine volume is maintained by the Na + K + ATPase pump in the basolateral membrane which hydrolyzes ATP and thus results in transport of Na + into the intercellular and interstitial spaces and increases movement of K + into cells. The increase in the Na + K + ATPase activity in diabetic rat results in increased urine flow (Ghule et al, 2012). We observed an increase in urine volume in STZ diabetic rats.…”

Section: Body Weight (G)supporting

confidence: 45%

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Ankita

Deepti

Nilam

2014

Pharmaceutical Biology

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Context: Different parts of Punica granatum Linn. (Punicaceae) are traditionally used as renal protective agents in the Indian system of medicine. However, there is paucity of information regarding its role in diabetic nephropathy. Objective: The present study investigates the nephroprotective potential of flavonoid-rich fraction of P. granatum leaves in streptozotocin (STZ)-induced early diabetic nephropathy in experimental animals. Materials and methods: Experimental diabetic nephropathy was induced in Wistar rats by single intraperitonial injection of STZ (65 mg/kg) dissolved in ice cold citrophosphate buffer (pH 4.3). After induction rats were divided into five groups (6 normal; 24 diabetic) and administered with glibenclamide (5 mg/kg) and three dose levels of flavonoid-rich fraction of P. granatum leaves (PGFF), i.e. 50, 100, and 200 mg/kg body weight/day for 28 d. Fasting blood glucose, lipid profile, serum albumin, serum total protein, serum creatinine, blood urea nitrogen (BUN) glycosylated hemoglobin, and biomarkers of kidney oxidative stress were assessed at the end of the treatment period. Urine was analyzed for the measurement of total protein, albumin, and creatinine clearance. Kidney sections were subjected to histopathological study. Results: Daily oral administration of variable dose levels of PGFF for 28 d normalized various biochemical, metabolic, and histopathological changes in the diabetic rats. PGFF significantly (p50.01 and p50.05) improved the glycemic status and renal function in diabetic rats as compared with diabetic control rats. Discussion and conclusion: The results of our study thus prove the protective effect of PGFF in early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals.

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“…Additionally, we have identified low concentrations of trigonelline in urine samples of patients with an altered renal function. This finding is reasonable because trigonelline is an alkaloid produced by the metabolism of niacin (vitamin B3), which is excreted in the urine and might protect against renal oxidative stress and apoptotic cell death and slow the progression of diabetic nephropathy [23]. To conclude, we have identified a set of urinary metabolites as good and non-invasive predictors of the eGFR levels, indicating that the urinary metabolome is a potential source for non-invasive markers of early renal dysfunction function.…”

Section: Discussionmentioning

confidence: 99%

Rule-Mining for the Early Prediction of Chronic Kidney Disease Based on Metabolomics and Multi-Source Data

Luck

Bertho

Bateson³

et al. 2016

PLoS ONE

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1H Nuclear Magnetic Resonance (NMR)-based metabolic profiling is very promising for the diagnostic of the stages of chronic kidney disease (CKD). Because of the high dimension of NMR spectra datasets and the complex mixture of metabolites in biological samples, the identification of discriminant biomarkers of a disease is challenging. None of the widely used chemometric methods in NMR metabolomics performs a local exhaustive exploration of the data. We developed a descriptive and easily understandable approach that searches for discriminant local phenomena using an original exhaustive rule-mining algorithm in order to predict two groups of patients: 1) patients having low to mild CKD stages with no renal failure and 2) patients having moderate to established CKD stages with renal failure. Our predictive algorithm explores the m-dimensional variable space to capture the local overdensities of the two groups of patients under the form of easily interpretable rules. Afterwards, a L2-penalized logistic regression on the discriminant rules was used to build predictive models of the CKD stages. We explored a complex multi-source dataset that included the clinical, demographic, clinical chemistry, renal pathology and urine metabolomic data of a cohort of 110 patients. Given this multi-source dataset and the complex nature of metabolomic data, we analyzed 1- and 2-dimensional rules in order to integrate the information carried by the interactions between the variables. The results indicated that our local algorithm is a valuable analytical method for the precise characterization of multivariate CKD stage profiles and as efficient as the classical global model using chi2 variable section with an approximately 70% of good classification level. The resulting predictive models predominantly identify urinary metabolites (such as 3-hydroxyisovalerate, carnitine, citrate, dimethylsulfone, creatinine and N-methylnicotinamide) as relevant variables indicating that CKD significantly affects the urinary metabolome. In addition, the simple knowledge of the concentration of urinary metabolites classifies the CKD stage of the patients correctly.

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Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats

Cited by 67 publications

References 40 publications

Urine Metabolomics by 1H-NMR Spectroscopy Indicates Associations between Serum 3,5-T2 Concentrations and Intermediary Metabolism in Euthyroid Humans

Urine Metabolomics by 1H-NMR Spectroscopy Indicates Associations between Serum 3,5-T2 Concentrations and Intermediary Metabolism in Euthyroid Humans

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Rule-Mining for the Early Prediction of Chronic Kidney Disease Based on Metabolomics and Multi-Source Data

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