Adverse effects of oxidative stress on renal cells and its prevention by antioxidants.
OBJECTIVE
Recent reports suggest that reactive oxygen species; e.g., hydrogen peroxide (H(2)O(2)), could be the primary cause of various drug-induced renal injuries. We investigated the effects of H(2)O(2) on renal cells to understand its mode of action and to explore cytoprotection from such a fatal injury.


METHODS
Renal proximal tubular LLC-PK(1) cells were exposed to various concentrations of H(2)O(2), and cell viability was determined at specified times. Lipid peroxidation assay and Western blot analysis of heat shock proteins (Hsp70 and Hsp90) were performed to assess the cellular effects.


RESULTS
The dose-response study showed that H(2)O(2) > or = 100 microM was severely cytotoxic. Even a 1-h exposure was sufficient to induce >95% cell death in 24 h. Lipid peroxidation was significantly (>50%) increased, while Hsp90, but not Hsp70, was partially degraded, to an approximately 85-kDa fragment, after a 3-h H(2)O(2) exposure. However, such cytotoxic cell death was remarkably ( approximately 90%) prevented by the antioxidants pyruvate or N-acetylcysteine (NAC), and Hsp90 remained intact.


CONCLUSIONS
Hydrogen peroxide-induced renal cell death involves increased lipid peroxidation and partial degradation of Hsp90. Both pyruvate and NAC are capable of detoxifying H(2)O(2) to maintain cell viability and Hsp90 integrity. Acute renal injuries associated with oxidative stress might preventable by appropriate antioxidants.
Nowzari
F B
FB
Department of Urology, New York Medical College, Valhalla, New York 10595, USA.
Davidson
S D
SD
Eshghi
M
M
Mallouh
C
C
Tazaki
H
H
Konno
S
S
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011773:Pyruvates / Q000494:pharmacology; D013552:Swine
D000975:Antioxidants; D018841:HSP90 Heat-Shock Proteins; D011773:Pyruvates; D008353:Mannitol; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D000111:Acetylcysteine