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Early evidence of global dna methylation and hydroxymethylation changes in rat kidneys consequent to hyperoxaluria-induced renal calcium oxalate stones

MEHRA Y., VISWANATHAN P.

 




Calcium supersaturation in urine during hyperoxaluria can lead to renal calcium oxalate (CaOx) stone deposition; a condition termed as nephrolithiasis. Recent genetic studies indicate the possibility of epigenetic alterations during nephrolithiasis. We aimed to study the influence of renal CaOx stone formation on the global levels of 5-methylcytosine (5 mC) and 5-hydroxymethycytosine (5 hmC) in hyperoxaluric rat kidney. In this study, twelve male Wistar rats were divided equally into two groups (control and experimental). Animals in the experimental group received 2.5 % (w/v) sodium oxalate in 5 ml of sterile water, every day, orally for four weeks to induce hyperoxaluria. At the end of four weeks, urine parameters, serum biochemistry and renal histopathological changes were evaluated. Global 5mC and 5hmC levels were analysed using enzyme-linked immune sorbent assay (ELISA), and renal mRNA expression of DNMTs and TET genes were also determined. Urine parameters and serum biochemistry showed that rats fed with 2.5 % (w/v) sodium oxalate orally for four weeks developed hyperoxaluria (p < 0.05). Histopathological evaluation of hyperoxaluric rat kidneys showed the deposition of CaOx crystals and marked tubular injury. ELISA showed significantly high levels of 5 hmC (p < 0.0001) in the kidneys of rats with renal CaOx stones, whereas 5 mC was only slightly significant (p < 0.05) as compared to the control rats. mRNA expression of TET 2, a regulator of DNA demethylation process, was found to be significantly upregulated (p < 0.01) in the rats with CaOx kidney stones. This preliminary study showed some early evidence of epigenetic modifications being influenced by hyperoxaluria-induced renal CaOx stones, which may likely contribute to the transcriptional regulation during CaOx nephrolithiasis.

Key words: Hyperoxaluria; kidney stones; DNA methylation; 5-methylcytosine; 5-hydroxymethylcytosine

Tsitologiya i Genetika 2022, vol. 56, no. 5, pp. 65-66

  • Renal Research Lab, Centre for Bio-Medical Research, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India

E-mail: pragasam.v vit.ac.in

MEHRA Y., VISWANATHAN P. Early evidence of global dna methylation and hydroxymethylation changes in rat kidneys consequent to hyperoxaluria-induced renal calcium oxalate stones, Tsitol Genet., 2022, vol. 56, no. 5, pp. 65-66.

In "Cytology and Genetics":
Yogita Mehra & Pragasam Viswanathan Early Evidence of Global DNA Methylation and Hydroxymethylation Changes in Rat Kidneys Consequent to Hyperoxaluria-Induced Renal Calcium Oxalate Stones, Cytol Genet., 2022, vol. 56, no. 5, pp. 458465
DOI: 10.3103/S0095452722050085


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