N-acetyl cysteine ameliorates ischemic renal failure

Area of Science:

• Nephrology
• Molecular Biology
• Biochemistry

Background:

• Ischemic renal injury recovery involves DNA synthesis and immediate early (IE) gene response in distinct cell populations.
• Cellular stress activates stress-activated protein kinases (SAPKs), inducing a non-proliferative IE response inhibitable by N-acetyl-L-cysteine (NAC).

Purpose of the Study:

• To determine if Jun NH2-terminal kinases (JNK), a type of SAPK, are activated during renal ischemia.
• To investigate whether NAC administration reduces the IE response and/or JNK activity in ischemic renal injury.

Main Methods:

• Administration of NAC (6 mM/kg body wt) before and after inducing renal ischemia.
• Measurement of c-fos and c-jun gene expression.
• Assay of JNK activity.
• Assessment of glomerular filtration rate (GFR) and kidney histology at 1 and 7 days post-ischemia.

Main Results:

• NAC reduced c-fos and c-jun expression by 50% and 70%, respectively.
• Ischemia-induced JNK activity was inhibited by NAC.
• NAC-treated animals showed significantly higher GFR at 1 and 7 days post-ischemia compared to controls.
• NAC improved kidney histology at 7 days but did not reduce proximal tubule necrosis at 24 hours.

Conclusions:

• The immediate early gene response in ischemic-reperfused kidneys is linked to the stress-activated kinase pathway.
• Part of this IE gene response appears detrimental to kidney function and cellular integrity.
• NAC ameliorates renal function loss, potentially via antioxidant properties or interaction with nitric oxide (NO).