Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors.
We previously reported that oxidative stress and renal tubular damage occur in chronic hyperoxaluric rats. However, the in vivo responses of renal epithelial cells after vitamin E administration and their correlations with calcium oxalate (CaOx) crystal formation have not been evaluated. Male Wistar rats received 0.75% ethylene glycol (EG) for 7, 21, or 42 days to induce CaOx deposition (EG group). Another group of EG-treated rats received 200 mg kg(-1) of vitamin E intraperitoneally (EG+E group) to evaluate its effect on hyperoxaluria. Urinary electrolytes and biochemistry and levels of lipid peroxides and enzymes were examined, together with serum vitamin E levels. Levels of the tubular markers, alpha and mu glutathione S-transferase, proliferating cell nuclear antigen (PCNA), osteopontinin (OPN), and Tamm-Horsfall protein (THP) were also measured, and TUNEL staining was performed to examine the viability of the tubular epithelium. There were no significant differences between the two age-matched controls either untreated or given vitamin E. Compared to untreated controls, tubular cell death was increased at all time points in EG rats with a gradual increase in CaOx crystals, whereas the number of PCNA-positive cells was only significantly increased on day 21. In EG+E rats, tubular cell death was decreased compared to the EG group, and cell proliferation was seen at all time points, while CaOx crystal deposition was decreased, but hyperoxaluria, urinary lipid peroxides, and enzymuria were unaffected. Vitamin E supplement prevented the loss of OPN and THP in renal tissues by EG and the reduction in their levels in the urine. The beneficial effect of vitamin E in reducing CaOx accumulation is due to attenuation of tubular cell death and enhancement of the defensive roles of OPN and THP.
Huang
H-S
HS
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Chen
J
J
Chen
C-F
CF
Ma
M-C
MC
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002129:Calcium Oxalate / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003460:Crystallization; D019855:Ethylene Glycol; D005982:Glutathione Transferase / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D007669:Kidney Calculi / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008054:Lipid Peroxides / Q000652:urine; D008297:Male; D009088:Mucoproteins / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D058949:Uromodulin; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D006023:Glycoproteins; D008054:Lipid Peroxides; D009088:Mucoproteins; C548614:Umod protein, rat; D058949:Uromodulin; C024229:osteopoietin; D014810:Vitamin E; D002129:Calcium Oxalate; D005982:Glutathione Transferase; D000118:Acetylglucosaminidase; D019855:Ethylene Glycol