Hyperoxaluria: The role of N‑acetyl‑L‑cysteine and Vitamin E on lithogenic factors and urinary markers in ameliorating calcium oxalate crystallization

  • Manjula Raman Department of Biochemistry, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, Tamil Nadu, India
Keywords: Antioxidants, Hyperoxaluria, Oxidative stress, Renal stones, Risk factors in urine

Abstract

Background and Aim: In hyperoxaluria, membrane injury is essential for the binding of oxalate or calcium oxalate (CaOx) crystal to be retained in the renal cell. This oxalate‑membrane interaction generates oxidative stress and is considered to be a significant causative factor of membrane damage and stone pathogenesis. The present study uses ammonium oxalate (AmOx) rat model to develop hyperoxaluria and lipid peroxidation, and N‑acetyl‑L‑cysteine (NAC) and NAC + Vitamin E given intraperitoneally to prevent CaOx crystal membrane damage and crystal binding. Methods: Stone forming risk factors namely, calcium, phosphate, oxalate, and inhibitors of stone formation namely, magnesium, uric acid, citrate, and glycosaminoglycans (GAGs) were studied and for renal function sodium, creatinine, and protein were seen in urine of five groups of animals (6 numbers each). The ratios of Ca/oxalate Mg/oxalate, citrate/calcium, oxalate/creatinine, and others are of clinical importance to assess the recurrence in stone formers. The CaOx supersaturation index and activity product (CaOx) index (rats) were studied as it indicates a high risk for stone formation. Further, the levels of oxalate synthesizing enzymes in liver and kidney were studied for endogenous synthesis of oxalate. Besides, urinary marker enzymes alkaline phosphatase, gamma glutamyl transferase, and lactate dehydrogenase (LDH) were studied indicating tissue membrane damage. Endogenous oxalate synthesizing enzymes of liver and kidney were done and also the tissue risk factors of stone. LDH isoenzyme gel electrophoresis and light microscopy of kidney tissue were done. Results: Urinary oxalate was increased significantly (P < 0.05) urinary calcium too, urinary magnesium was significantly decreased (P < 0.01), urinary citrate levels were found to be 1.43 ± 0.15 mg/24 h in control animals but decreased 3‑fold in AmOx‑treated animals. Urinary marker enzymes showed injured epithelium, a prerequisite for crystal adhesion and decreased GAGs in urine showed damage to the proximal convoluted tubules. LDH 2 isoenzyme as a marker of kidney tissue damage was found increased in hyperoxaluric rats. Levels of urinary GAGs were decreased significantly (P < 0.001). NAC and Vitamin E pretreated animals showed a significant decrease in stone forming risk factors in urine and increased inhibitor excretion. Histological sections showed NAC and Vitamin E pretreated hyperoxaluric rats inhibited deposition of CaOx crystals and renal cell damage. Conclusion: NAC therapy prevents CaOx retention by protecting against membrane injury, thus maintaining a smooth urothelium that does not favor stone formation.

Published
2016-04-30
How to Cite
Raman, M. (2016). Hyperoxaluria: The role of N‑acetyl‑L‑cysteine and Vitamin E on lithogenic factors and urinary markers in ameliorating calcium oxalate crystallization. International Journal of Clinical and Experimental Physiology, 3(2), 82-91. Retrieved from http://ijcep.org/index.php/ijcep/article/view/268