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Modulation of gentamicin nephrotoxicity by chronic inhibition of angiotensin-I-converting enzyme in rat
Abstract:
Perindopril, a new specific and potent inhibitor of angiotensin-I-converting enzyme, was used to evaluate the possible participation of inhibition of the renin-angiotensin system in the development of aminoglycoside-induced renal failure. Kidney function, morphology and biochemistry were evaluated at regular intervals throughout the study. Perindopril was given orally to rats at a daily dose of 2 mg/kg for 15 days prior to and during 15-day gentamicin treatment given intraperitoneally at a daily dose of 50 mg/kg. Perindopril treatment alone induced no modification in renal function or structure. Gentamicin treatment alone induced typical renal lesions which were scored as moderate and a slight but significant decrease in ACE blood levels. Concurrent treatment with perindopril and gentamicin induced a greater drop in ACE blood levels than after the administration of perindopril alone and produced more marked renal impairment than after the administration of gentamicin alone. These observations suggest that the integrity of the renin-angiotensin system may play an important role in limiting kidney injury during aminoglycoside-induced nephrotoxicity.
Insights
Inhibiting the renin-angiotensin system with perindopril worsened gentamicin-induced kidney damage in rats. This suggests the renin-angiotensin system helps protect kidneys from aminoglycoside nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Aminoglycoside antibiotics can cause kidney damage (nephrotoxicity).
- The renin-angiotensin system plays a role in regulating blood pressure and kidney function.
- The exact mechanisms of aminoglycoside-induced renal failure are not fully understood.
Purpose of the Study:
- To investigate the role of the renin-angiotensin system in aminoglycoside-induced renal failure.
- To evaluate the effect of perindopril, an angiotensin-converting enzyme (ACE) inhibitor, on gentamicin nephrotoxicity.
Main Methods:
- Rats were treated with perindopril (an ACE inhibitor) and/or gentamicin (an antibiotic).
- Kidney function, morphology, and biochemistry were assessed.
- Blood levels of angiotensin-converting enzyme (ACE) were measured.
Main Results:
- Perindopril alone did not affect kidney function or structure.
- Gentamicin alone caused moderate kidney lesions and a slight decrease in ACE blood levels.
- Concurrent perindopril and gentamicin treatment resulted in lower ACE levels and more severe kidney impairment compared to gentamicin alone.
Conclusions:
- Inhibition of the renin-angiotensin system exacerbates aminoglycoside-induced nephrotoxicity.
- The integrity of the renin-angiotensin system appears crucial for limiting kidney injury during aminoglycoside treatment.
- Targeting the renin-angiotensin system might be a strategy to mitigate aminoglycoside-induced kidney damage.