Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.
BACKGROUND
Animals treated with gentamicin can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases and macrophages in the renal cortex and structural and functional renal changes of rats treated with gentamicin or gentamicin + pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor.


METHODS
38 female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, 38 with gentamicin + PDTC, and 28 with 0.15 M NaCl solution. The animals were killed 5 and 30 days after these injections and the kidneys were removed for histological and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining. The fractional interstitial area was determined by morphometry.


RESULTS
Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. Increased ED-1, MAP kinases and NF-kappaB staining were also observed in the renal cortex from all gentamicin-treated rats compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis in the renal cortex despite the recovery of renal function. Treatment with PDTC reduced the functional and structural changes induced by gentamicin.


CONCLUSIONS
These data show that inhibition of NF-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.
Volpini
Rildo A
RA
Department of Physiology, Faculty of Medicine, Ribeirão Preto, Brazil.
Costa
Roberto S
RS
da Silva
Cleonice G A
CG
Coimbra
Terezila M
TM
D000818:Animals; D003404:Creatinine / Q000097:blood; D005260:Female; D005839:Gentamicins; D007150:Immunohistochemistry; D007668:Kidney / Q000503:physiopathology; D007672:Kidney Cortex / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology
D005839:Gentamicins; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D003404:Creatinine; D020928:Mitogen-Activated Protein Kinases