Urinary transferrin and proinflammatory markers predict the earliest diabetic nephropathy onset

Ahmed, Soliman; Aziz, Wessam M; Shaker, Sylvia E.; Fayed, Dalia B.; Shawky, Heba

doi:10.1080/1354750x.2021.2023639

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…The early signs of renal nephropathy were pronounced in the untreated diabetic animals after two weeks of DM induction and maintained an escalating pattern in line with progressive hyperglycemia. Of note, the dynamics of renal injury observed herein were completely different from that previously reported by Ahmed et al [32], which can be expected given the higher susceptibility of SD rats to the STZ diabetogenic effect attributed to their inherent hypertensive nature [34].…”

Section: Discussioncontrasting

confidence: 97%

“…In contrast to our previous report [32], a single STZ dose was sufficient to establish a persistent hyperglycemia in Sprague Dawley (SD) rats, which was manifested by the excessive polyuria, accelerated rate of weight loss, and higher consumption of food and water among other classical signs of diabetes mellitus observed one week after the STZ induction. Worthy mentioning, the assessment of renal injury/nephropathy markers was initiated two weeks after the induction of DM, to bypass the transient nephrotoxic effect of STZ and guarantee that the induced renal injury is hyperglycemia-associated [33].…”

Section: Discussioncontrasting

confidence: 95%

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Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ–mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats

Aziz,

Ahmed,

Shaker

et al. 2024

Diabetol Metab Syndr

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Background & objective : While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed to assess the renoprotective potentials of methanol (MO) and methylene chloride (MC) fixed oil extracts of purslane seeds in a diabetic nephropathy (DN) model. Methods Purslane seeds were extracted using absolute methanol and methylene chloride, and type-1 diabetes was induced with a single 55 mg/kg dose of Streptozotocin (STZ) dissolved in 100 mmol/L citrate buffer (pH 4.5), and then diabetic animals were received MO, MC, for 42 consecutive days to compare their antidiabetic effect relative to the reference drug “Losartan”. Renal functions and DN biomarkers were weekly assessed, and the relative expression of different oxido-inflammatory mediators was quantified in diabetic kidneys by RT-PCR. Data were statistically analyzed using GraphPad Prism 9.0.2. Results The oral administration of MO and MC extracts (250 mg/kg/day) significantly ameliorated the body weight loss (P < 0.0001 / each), fasting blood glucose levels (FBG) (P < 0.0001 / each), urine volume (P < 0.0001 / each), as well as serum creatinine (P < 0.0001 / each), uric acid (P = 0.0022, 0.0052), and blood urea nitrogen (BUN) (P = 0.0265, 0.0338); respectively, compared with the untreated diabetic rats. In addition, both extracts restored the effectuality of antioxidative machinery in diabetic kidneys as indicated by a significant reduction of ROS accumulation and lipid peroxidation; higher GSH content, and promoted activity of glutathione reductase and superoxide dismutase antioxidant enzymes (P < 0.0001 / each). Histologically, both extracts alleviated the DN-structural alterations including the glomerular congestion and tubular degeneration, with MC-treated kidneys showing near to normal architecture. The transcription profiles of all treated kidneys revealed a significantly downregulated expression of TNF-α, IL-6, Keap1 and NF-κB genes, concomitant with a significant upregulation of SDF-1, IL-10, Nrf2, HO-1, and PPARγ gene expression (P < 0.0001 / all). Conclusion These findings highlight the remarkable DN-prophylactic potentials of purslane extracts mediated by neutralizing the hyperglycemia-induced ROS accumulation, and circumventing the downstream inflammatory cascades, surpassing the reference angiotensin receptor blocker; i.e. Losartan.

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Section: Discussioncontrasting

confidence: 97%

Section: Discussioncontrasting

confidence: 95%

Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ–mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats

Aziz,

Ahmed,

Shaker

et al. 2024

Diabetol Metab Syndr

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Discrepancies between transcutaneous and estimated glomerular filtration rates in rats with chronic kidney disease

Pieters,

Besseling,

Bovée

et al. 2024

Kidney International

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Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients

Chen,

Peng,

Sun

et al. 2023

Renal Failure

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Background The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. Methods Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. Results Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased ( p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1β, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764–0.924). Conclusion Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes.

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Urinary transferrin and proinflammatory markers predict the earliest diabetic nephropathy onset

Cited by 4 publications

References 30 publications

Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ–mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats

Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ–mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats

Discrepancies between transcutaneous and estimated glomerular filtration rates in rats with chronic kidney disease

Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients

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