[Relationship between glomerular nephrin expression and oxidative stress reaction in rats with adriamycin-induced nephrosis].
OBJECTIVE
It has been proposed that nephrotic syndrome is a consequence of an imbalance between oxidant and anti-oxidant activity. Nephrin plays an important role in maintaining glomerular filtration barrier. This study aimed to explore the relationship between the expression of glomerular nephrin and oxidative stress reaction in rats with adriamycin (ADR)-induced nephrosis, and the protection of prednisone and vitamin E against renal injuries.


METHODS
Nephrosis was induced by single intravenous injection of ADR (5 mg/kg). The prednisone intervention group was administered with prednisone (10 mg/kg daily) between 1 and 4 weeks after ADR injection. The vitamin E intervention group received vitamin E of 20 mg/kg daily from 1 week before ADR injection till to 4 weeks after ADR injection. Control rats were intravenously injected with normal saline. After 7, 14, 21 and 28 days of ADR injection, the indexes of oxidative stress reaction of the renal cortex, malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidative capacity (T-AOC), were measured using the chemical chromatometry. The protein expression of glomerular nephrin was measured by immunohistochemistry.


RESULTS
Prednisone or vitamin E treatment reduced urinary protein from 14 days to 28 days after ADR injection. MDA levels of renal cortex increased, while renal activities of SOD and T-AOC as well as nephrin protein contents decreased in untreated nephrosis group from 7 days after ADR injection compared with those in the control rats. Compared with the untreated nephrosis group, prednisone treatment resulted in an increase in nephrin protein contents 28 days after ADR injection; Vitamin E treatment decreased renal MDA levels and increased renal activities of SOD and T-AOC and nephrin protein contents 28 days after ADR injection. Nephrin staining showed a sable linear-like pattern along the capillary loops of glomerulus in the control rats. Nephrin staining presented a light tan discontinuous short linear-like or punctiform pattern along the capillary loops of glomerulus in the untreated ADR group. Prednisone or vitamin E treatment ameliorated abnormal expression of nephrin induced by nephrosis. Glomerular nephrin expression level was negatively correlated with renal MDA level and positively correlated with renal activities of SOD and T-AOC.


CONCLUSIONS
A reduction of glomerular nephrin expression is closely related to oxidative stress reaction. Prednisone and vitamin E have protective effects against renal injuries induced by ADR in rats.
Zhu
Ying
Y
Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Lu
Ling
L
D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis*; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D018384:Oxidative Stress; D011241:Prednisone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D008565:Membrane Proteins; C113267:nephrin; D014810:Vitamin E; D008315:Malondialdehyde; D004317:Doxorubicin; D013482:Superoxide Dismutase; D011241:Prednisone