Kidney injury induced by lipid peroxide produced by vitamin E deficiency and GSH depletion in rats.

Abstract

Four-week-old Wistar male rats were fed a vitamin E (VE) deficient (OE) or a VE-sufficient (10E) diet for 6 weeks and then intra peritoneally treated with buthionine sulfoximine (BSO) at 1mmol/kg body weight once a day for 3days. Glutathione (GSH) depletion by BSO treatment caused injuries especially in the kidneys of VE-deficient rats. The kidney weight increased in the VE-deficient rats after BSO treatment (OE-BSO). It was observed that the epithelial cells of the renal tubules in this group were strongly impaired and the injuries were necrosis and desquamation. No injury was observed in the kidneys of the BSO-untreated OE group and the 10E groups. The TBA value of the kidney of OE-BSO group was lower than that of the BSO-untreated 0E group, but the lipofuscin content of the kidney of the OE-BSO group was 10 times higher than that of the BSO-untreated OE group. These results suggest that the kidney injuries in rats may be caused by lipid peroxidation induced by vitamin E deficiency and glutathione depletion. Key Words kidney injury, lipid peroxide, vitamin E deficiency, GSH depletion, DL-buthionine sulfoximine Vitamin E (VE) is considered to function as an important cellular antioxidant. Alpha-tocopherol, a component of YE, inhibits in vitro lipid peroxidation in a variety of membrane systems (1-3). Several lines of evidence suggest that alpha tocopherol exerts its antioxidant activity by scavenging free radicals generated in lipid peroxidation (4).

Changes in Serum Levels of Creatol and Methylguanidine in Renal Injury Induced by Lipid Peroxide Produced by Vitamin E Deficiency and GSH Depletion in Rats

“…1). As described previously [7], the total amount of GSH decreased 1 day after administration of BSO to 14% of the level in rats on day 0. The level of TBA in kidneys decreased gradually.…”

“…In a previous study, we demonstrated that lipid peroxi dation induced by vitamin E deficiency and depletion of GSH in rats caused injury to the kidneys (acute tubular necrosis [7], After treatment of rats with BSO, levels of GSH in serum, liver and kidney decreased to 10-13% of the control levels. Depletion of GSH by treatment with BSO did not, by itself, cause acute tubular necrosis.…”

“…Histological studies on day 3 revealed necrosis, desquamation and hyalinization in renal proximal tubules at the corticomedullary junction of all vitamin-E-deficient rats that had been treated with BSO ( fig. 3) as described previously [7], Table 1 shows the time course of changes in levels of guanidino compounds in the serum of rats treated with BSO. Creatol, MG and GSA were not detected on day 0.…”

“…A vitamin-E-deficient diet was prepared as described previously [7]. Commercial safflower oil that had been treated with powdered activated charcoal was used as vitamin-E-deficient oil [12], and a mixture of vitamins without vitamin E was prepared that was based on the composition of a defined mixture of vitamins (AIN-76).…”

“…which is a specific inhibitor of y-glutamylcysteine synthe tase, did not cause anatomical disruption in isolated per fused kidneys from adult rats [5], Nath et al [6] demon strated that dietary deficiency of vitamin E and selenium, which is a cofactor of glutathione peroxidase, exacerbated ischemic injury in the rat kidney. Therefore, in a previous study, we examined the effect of depletion of GSH by treatment with BSO of vitmin-E-deficient rats without ischemia and we found that it induced acute tubular necrosis [7], In this system, formation of lipofuscin was enhanced and this enhancement implied that lipid peroxi dation might have played an important role in the injury to the kidney [7].…”