Korean J Nephrol.  2007 Nov;26(6):660-668.

Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney

• Bae EH
• Kim IJ
• Oh YW
• Bae WK
• Park JW
• Ma SK
• Kim NH
• Choi KC
• Lee JU
• Kim SH
• Kim SW

Abstract

PURPOSE: An altered activity of vasoactive hormones as well as aldosterone synthase (CYP11B2) in the kidney may involve the pathogenesis of gentamicin-induced nephropathy. The present study was designed to investigate whether there are changes of local renin-angiotensin-aldosterone system (RAAS) and endothelin (ET) in the kidney of gentamicin-induced nephropathy in rats.
METHODS
Male Sprague-Dawley rats (180-200 g) were intramuscularly injected with gentamicin (100 mg/kg per day) for 5 days. Vehicle was given for the control rats. The mRNA expression of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET system and transforming grow factor-beta1 (TGF-beta1) was determined in the kidney by real-time polymerase chain reaction. The protein expression of TGF-beta in the kidney was determined by immunoblotting and immunohistochemistry.
RESULTS
Following the gentamicin treatment, a renal failure was noted as evidenced by increased serum concentrations of creatinine along with a decrease of its clearance. TGF-beta1 expression was significantly increased in the kidney in gentamicin treated rats compared with that in controls. The abundance of ET-1 mRNA was significantly increased. The endothelin type A receptor expression was decreased while endothelin type B receptor was not changed. The expression of angiotensin converting enzyme 1 (ACE1) and ACE2 was decreased, whereas renin expression was not changed. The CYP11B2 expression was significantly increased in gentamicin treated rats, while mineralocorticoid receptor expression was not changed.
CONCLUSION
The expression of ET-1 and CYP11B2 was up-regulated which may play a role in the pathogenesis of gentamicin-induced nephropathy.

Keyword

Gentamicin; Endothelin; Aldosterone synthase; Transforming growth factor-beta1

MeSH Terms

Aldosterone Synthase*
Animals
Creatinine
Endothelin-1*
Endothelins
Gentamicins
Humans
Immunoblotting
Immunohistochemistry
Kidney*
Male
Peptidyl-Dipeptidase A
Rats*
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Receptors, Mineralocorticoid
Renal Insufficiency
Renin
Renin-Angiotensin System
RNA, Messenger
Transforming Growth Factor beta
Transforming Growth Factor beta1
Aldosterone Synthase
Creatinine
Endothelin-1
Endothelins
Gentamicins
Peptidyl-Dipeptidase A
RNA, Messenger
Receptors, Mineralocorticoid
Renin
Transforming Growth Factor beta
Transforming Growth Factor beta1