Limitation of apoptotic changes in renal tubular cell injury induced by hyperoxaluria

• Published in: Urolithiasis 2004-08, Vol.32 (4), p.271-277
• Main Authors: Sarica, Kemal, Erbagci, Ahmet, Yağci, Faruk, Bakir, Kemal, Erturhan, Sakip, Uçak, Ramazan
• Format: Article
• Language: English
• Subjects: Allopurinol - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Cells; Cells, Cultured - drug effects; Disease Models, Animal; Hyperoxaluria - pathology; In Situ Nick-End Labeling; Kidney Tubules - cytology; Kidney Tubules - drug effects; Male; Oxalates; Potassium Citrate - pharmacology; Rabbits; Random Allocation; Reference Values; Sensitivity and Specificity; Urinary Calculi - pathology; Urinary Calculi - ultrastructure; Urothelium - pathology; Verapamil - pharmacology; Vitamin E - pharmacology
• ISSN: 0300-5623; 2194-7228; 1434-0879; 2194-7236
• DOI: 10.1007/s00240-003-0393-3

Renal tubular epithelium is the major target for oxalate induced injury, and sustained hyperoxaluria together with CaOx crystal formation/deposition may induce renal tubular cell damage and/or dysfunction. This may express itself in cell apoptosis. To evaluate the possible protective effects of certain agents (vitamin E, potassium citrate, allopurinol, verapamil and MgOH) on the presence and the severity of apoptotic changes caused by hyperoxaluria on renal tubular epithelium, an experimental study in rabbits was performed. Seventy rabbits were divided into seven different groups (each group n = 10): in group I severe hyperoxaluria was induced by continuous ethylene glycol (0.75%) administration started on day 0 and completed on day 14. Histologic alterations including crystal formation together with apoptotic changes (by using the TUNEL method) were evaluated on days 21 and 42, respectively. In the remaining experimental groups (groups II-VI), animals received some agents in addition to the induction of hyperoxaluria in an attempt to limit apoptotic changes. Group VII) animals constituted the controls. Kidneys were examined histopathologically under light microscopy for the presence and degree of crystal deposition in the tubular lumen. The percentage of apoptotic nuclei in the control group was significantly different from the other group animals (2.9-2.4%) in all study phases (P < 0.05). Apart from potassium citrate and allopurinol, the other medications seemed to prevent or limit the formation of apoptotic changes in renal tubular epithelium during the early period (day 21). The percentage of positively stained nuclei in animals undergoing potassium citrate medication ranged from 24.3% to 28.6%, with an average of 27.1%. This was 18.4% in animals receiving allopurinol. On the other hand, animals receiving magnesium hydroxide (MgOH), verapamil and vitamin E demonstrated limited apoptotic changes (11.2, 9.7, 8.7%, respectively) during this phase(P < 0.05). In the long-term (day 42), the animals receiving allopurinol and vitamin E showed a decrease in the percentage of the positively stained nuclei (13.5% and 8.3%, respectively). Animals in the other groups showed an increase in the number and percentage of apoptotic cells. Although, there was a significant decrease in the mean values of apoptosis in animals receiving vitamin E (8.7%-8.3%) and allopurinol (18.4%-13.5%) (P < 0.05), animals on verapamil, MgOH and potassium citrate medication had an increase