α-Tocopherol modulates lipoprotein cytotoxicity in obstructive nephropathy

Abstract

Oxidative stress in unilateral ureteral obstruction (UUO) contributes to the development of glomerular and tubulointerstitial lesions. The present study investigated whether oxidized low-density lipoprotein (oLDL) contributes to the pathogenesis of kidney injury in UUO, and whether alpha-tocopherol modulates such cytotoxicity and promotes repair. Male Sprague-Dawley rats weighing 100-125 g were assigned to three groups of 6 animals each: (1) sham, regular chow; (2) UUO, regular chow; and (3) UUO, alpha-tocopherol supplementation. We found a significant increase in the level of oxidative stress in the UUO group as measured by malondialdehyde (MDA) content in both plasma and kidneys. The LDL isolated from this group was cytotoxic to rat mesangial cells. The level of oxidation and cytotoxicity was significantly reduced when animals were treated with alpha-tocopherol. Plasma cholesterol concentration, kidney MDA, and transforming growth factor beta1 mRNA expression were all significantly increased in the UUO animals, and partially reduced in alpha-tocopherol-treated animals. Our data suggest that oxidative modification of LDL is associated with the renal injury in UUO. Taken together, our data support the concept that alpha-tocopherol can modulate LDL oxidation and its cytotoxic effects on rat mesangial cells in vitro.

LIM homeobox transcription factor 1B expression affects renal interstitial fibrosis and apoptosis in unilateral ureteral obstructed rats

“…Furthermore, Kida et al and Sato et al determined that a positive linear relationship exists between tubular dilatation and tubular epithelial apoptosis in UUO mice (18). Increased ROS, lipid peroxidation, and compromised antioxidants were previously found in a number of studies using obstructed rodent kidneys (6,24,35,48), and ROS have been suggested to impair the integrity of the glomerular basement membrane, reduce podocyte proteoglycan de novo synthesis, and stimulate factors promoting ECM deposition, including TGF-␤ 1 (9), as similarly observed in the present study. Overall, these results corroborate our results in the RTEC model system.…”

The Effect of Eriobotrya japonica Seed Extract on Oxidative Stress in Adriamycin-Induced Nephropathy in Rats

“…[15][16][17][18][19][20] In addition, studies have reported that the antioxidant vitamin E and the antihypercholesterolemic agent probucol reduce nephrotoxicity. 21,22) However, few drugs with antioxidant activity are clinically available, and such drugs are not used for antioxidant purposes. In this study, we investigated the physiological action and mechanism of action of ESE on ADR nephropathy, which was considered to be strongly influenced by oxidant stress.…”

Antioxidants: A Possible Role in Kidney Protection

“…Downregulation of renal TGF-ß1 expression was also demonstrated in some reports [75,76], but not in all [77]. Nephroprotective effects of ·-tocopherol include attenuation of renal structural and functional alterations in IgA nephropathy [75], retardation of development of glomerulosclerosis in a remnant kidney model [78] and many others (table 2) [67,68,75,[78][79][80][81][82][83][84]. In one uncontrolled clinical study, vitamin E administration decreased proteinuria in children with FSGS [85].…”