Association of circulatory asymmetric dimethylarginine (ADMA) with diabetic nephropathy in Asian Indians and its causative role in renal cell injury

Jayachandran, Isaivani; Sundararajan, Saravanakumar; Prabu, Paramasivam; Venkatesan, Balachandar; Subramanian, Shanthirani C.; Balasubramanyam, Muthuswamy; Mohan, Viswanathan; Manickam, Nagaraj

doi:10.1016/j.clinbiochem.2017.05.007

Cited by 16 publications

(14 citation statements)

References 37 publications

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“…Further, we reported that the circulatory levels of nitric oxide were proportionately reduced with the increased levels of ADMA in diabetes patients with albuminuria and thus we reported a negative correlation between ADMA and nitric oxide levels 8 . These studies and the results of the present manuscript emphasize a role of ADMA in the NOS and nitric oxide regulation.…”

Section: Discussionmentioning

confidence: 48%

“…In our previous report, we have shown that under high glucose condition, the ADMA metabolizing enzyme DDAH 1 activity was significantly reduced resulting in the increase in the intracellular concentration of ADMA 8 . Further, we have shown that ADMA levels are increased in type 2 patients with albuminuria and it can be used as a prognostic biomarker for diabetic kidney disease 8 .…”

Section: Introductionmentioning

confidence: 89%

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Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway

Jayachandran

Sundararajan

Venkatesan

et al. 2020

Sci Rep

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We previously reported that the circulatory level of Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, was increased in diabetic kidney disease patients. However, the mechanism and the role of ADMA in diabetic kidney injury remain unclear. Hence, our principal aim is to investigate the causal role of ADMA in the progression of renal cell fibrosis under high glucose (HG) treatment and to delineate its signaling alterations in kidney cell injury. High Glucose/ADMA significantly increased fibrotic events including cell migration, invasion and proliferation along with fibrotic markers in the renal cells; whereas ADMA inhibition reversed the renal cell fibrosis. To delineate the central role of ADMA induced fibrotic signaling pathway and its downstream signaling, we analysed the expression levels of fibrotic markers, NOX4, ROS and ERK activity by using specific inhibitors and genetic manipulation techniques. ADMA stimulated the ROS generation along with a significant increase in NOX4 and ERK activity. Further, we observed that ADMA activated NOX-4 and ERK are involved in the extracellular matrix proteins accumulation. Also, we observed that ADMA induced ERK1/2 phosphorylation was decreased after NOX4 silencing. Our study mechanistically demonstrates that ADMA is involved in the progression of kidney cell injury under high glucose condition by targeting coordinated complex mechanisms involving the NOX4- ROS-ERK pathway.

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Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 89%

Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway

Jayachandran

Sundararajan

Venkatesan

et al. 2020

Sci Rep

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“…10 Most of the study subjects in the group of normal ADMA level in this study experienced dyslipidemia (59.1%). Dyslipidemia was one of the risk factors for endothelial 15 However, in the group of high ADMA level, the majority of the study subjects (61.3%) did not experience dyslipidemia and did not affect the increase of ADMA level. The results of this study were similar to Ozdogan et al, study who showed no difference between cholesterol, triglyceride, HDL, and LDL variables with ADMA level (p > 0.05).25 Normal levels of cholesterol, and triglycerides in the group of high ADMA level can be caused by anti-cholesterolemia/antitriglyceridemic therapy as well as a good diet.…”

Section: Resultsmentioning

confidence: 86%

“…The cut-off level was 0.66 μmol/L, determined based on a prior research conducted by Jayachandran et al, about diabetes mellitus patients from Asian race by using ADMA examination method, namely micro ELISA. 15 Table 1 below showed the research subject characteristics between the two groups.…”

Section: Resultsmentioning

confidence: 99%

Differences of Asymmetric Dimethyl Arginine Level in Patients With Diabetic Nephropathy and Non-Diabetic Nephropathy

Wisudawati

Rita

Lismayanti

et al. 2018

Indonesian J. Clin. Pathol. Med. Lab.

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Endothelial dysfunction occurs early in Diabetic Nephropathy (DN), characterized by elevated Asymmetric Dimethylarginine (ADMA) levels. Increased ADMA levels may inhibit endothelial Nitric Oxide Synthase (eNOS) production which are required for Nitric Oxide (NO) formation. Decreased NO levels can increase peripheral resistance and exacerbate the endothelial dysfunction. By knowing the difference of ADMA levels in DN and non-DN patients can help the follow-up and management for the progression of endothelial dysfunction. The purpose of this research was to know the difference of ADMA levels in DN and non-DN by a cross-sectional observational analytical method in 53 diabetes mellitus patients at the Dr. Hasan Sadikin Hospital Bandung (December 2016-July 2017). Urine samples were examined to calculate urinary creatinine albumin ratio (uACR) and serum for ADMA levels. Asymetric dimethylarginin was examined by micro ELISA. Most of the subjects were males (60.38%) with the highest age in the range of 55-64 years (45.28%). Increased ADMA levels were found in 100% of DN and 18.5% of non-DN. Median ADMA levels were found in DN 1.01(0.73-2.25) µmol/L and non-DN 0.57(0.27-1.17) µmol/L, showing a significant difference of ADMA levels (p<0.001). High ADMA levels showed endothelial dysfunction in DN. Serum ADMA levels in DN patients were higher than in non-DN.

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“…Serum ADMA levels were higher in patients with diabetic retinopathy compared to the control group, but there was no elevation in the vitreous ADMA level. In the literature, there are many studies on plasma ADMA levels in patients with Type 2 diabetes mellitus [11,[14][15][16]. Krzyzanowska et al [16] measured the level of plasma ADMA and homocysteine in 136 patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Investigated of vitreous and serum Asymmetric Dimethylarginine levels in diabetic retinopathy

Alpay

Özcan

Uğurbaş

et al. 2019

Preprint

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Purpose To investigate the intravitreal and blood Asymmetric dimethylarginine (ADMA) level in diabetic retinopathy (DR). Materials and Methods Twenty eyes of 20 patients with DR with the decision of vitrectomy, and 20 eyes of 20 patients without diabetes as a control group were included in the study. During vitrectomy, vitreous and minimum 3ml peripheral blood samples were taken simultaneously. Serum and vitreous ADMA levels were compared between the two groups. Results The serum ADMA level was higher in the diabetic group compared to the non-diabetic group (p=0,009). However, there was no statistically significant difference between the mean vitreous ADMA levels. There was no correlation between serum and vitreous ADMA levels. Conclusion In patients with diabetic retinopathy, serum ADMA levels increased, but no increase in vitreous ADMA levels was detected.

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Association of circulatory asymmetric dimethylarginine (ADMA) with diabetic nephropathy in Asian Indians and its causative role in renal cell injury

Cited by 16 publications

References 37 publications

Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway

Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway

Differences of Asymmetric Dimethyl Arginine Level in Patients With Diabetic Nephropathy and Non-Diabetic Nephropathy

Investigated of vitreous and serum Asymmetric Dimethylarginine levels in diabetic retinopathy

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