Role of myofibroblasts, macrophages, transforming growth factor-beta endothelin, angiotensin-II, and fibronectin in the progression of tubulointerstitial nephritis induced by gentamicin.
BACKGROUND
Animal models of aminoglycoside nephrotoxicity can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of fibronectin, alpha-smooth muscle actin (alpha-SM-actin), macrophages, endothelin,transforming growth factor-beta (TGF-beta) and angiotensin II (AII) in the renal cortex of rats, 5 and 30 days after stopping treatment with gentamicin, and the relationships with the histological features and renal function of these animals.


METHODS
Forty-five female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, and 11 controls were injected with 0.15 M NaCl solution. The animals were killed 5 or 30 days after these injections and the kidneys removed for histological examination, enzyme immunoassay and immunohistochemical studies. The histological and immunohistochemical results were evaluated by scores reflecting the extent of lesion or staining. The percentage of tubulointerstitial lesions was determined by morphometry.


RESULTS
Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. The immunohistochemical studies showed increased fibronectin, alpha-SM-actin, ED-1, endothelin, TGF-beta and AII staining in the renal cortex from rats 5 and 30 days after gentamicin compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis and increased TGF-beta content in the renal cortex (p < 0.001), despite the recovery of renal function. The proportion of damaged areas was 23.17% +/- 5.23 in the renal cortex of these animals.


CONCLUSIONS
Macrophages, myofibroblasts, TGF-beta, endothelin and AII may have contributed to the development of renal fibrosis in these rats.
Geleilete
Tufik J
TJ
Department of Internal Medicine, Faculty of Medicine, Ribeirao Preto, SP, Brazil.
Melo
Guilherme C
GC
Costa
Roberto S
RS
Volpini
Rildo A
RA
Soares
Telma J
TJ
Coimbra
Terezila M
TM
D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D018450:Disease Progression; D016232:Endothelins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005839:Gentamicins; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000473:pathology* / Q000503:physiopathology; D011336:Probability; D011379:Prognosis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015415:Biomarkers; D016232:Endothelins; D005353:Fibronectins; D005839:Gentamicins; D016212:Transforming Growth Factor beta; D000804:Angiotensin II