Renoprotective effect of N-acetylcysteine depends upon the severity of the ischemia reperfusion injury

Abstract

Acute kidney injury (AKI) is a common complication in seriously ill patients, while renal ischemia-reperfusion (I/R) injury is the most frequent event in this oxidative renal injury. N-acetylcysteine (NAC) is a small molecule containing a thiol group that has antioxidant properties, promoting detoxification and acting directly as a free radical scavenger. In this study, the protective effect of NAC was investigated in short-term (30 min) and long-term (45 min) ischemic AKI. This was achieved via clamping of the renal artery for 30 or 45 min in Wistar rats to induce I/R injury. AKI worsened with a longer period of ischemia (45 compared to 30 min) due to probable irreversible damage. Preconditioning with NAC in short-term ischemia improved renal blood flow and increased creatinine clearance by reducing oxidative metabolites and increasing antioxidant capacity. Otherwise, NAC did not change these parameters in the long-term ischemia. Therefore, this study demonstrated that the period of ischemia determines the severity of the AKI, and NAC presented antioxidant effects in short-term ischemia but not in long-term ischemia, confirming that there is a possible therapeutic window for its renoprotective effect.

Hydrogel and nanoparticle carriers for kidney disease therapy: trends and recent advancements

“…[17] Amino acids/ Peptides/ Proteins N-acetylcysteine (NAC) Antioxidant Unspecific tissue/organ uptake, skin reactions, immune system and neurological interactions. [11] Atrial natriuretic peptide (ANP) Antioxidant Unspecific tissue/organ uptake with adverse reactions noted relating to cardiac tissues. [13] Immunosuppressant (cyclosporin A)…”

“…As well as hemodynamics and oxygen transport. For these therapeutic outcomes, there are existing interventions that have been employed within clinical settings, including: Trimetazidine [9], forced diuresis with matched hydration during surgery [10], N-acetylcysteine [11], HMG Co-A reductase inhibitors (statins) [12] and atrial natriuretic peptide (ANP) [13]. There are also other therapeutic candidates that are within earlier stages of clinical development, including: immunosuppressant (cyclosporin A) [14], antioxidants (iron chelators [15], heme arginate [16]), vasodilators (levosimendan) [17], tissue repair agents (synthetic oligopeptide THR-184 [18]).…”

“…Similarly, N-acetylcysteine (NAC) is another commonly employed therapeutic for patients with renal impairment that demonstrates unspecific tissue uptake. NAC is a small thiol-containing and amino acid-derived molecule with free radical scavenging properties and has potential protective actions in kidney injuries [11]. However, studies on the uptake and distribution of NAC in mice showed multiple sites of uptake, including in the liver, kidneys, gastrointestinal mucosa, salivary glands, and to a lesser extent, within bone marrow and the spleen [21].…”

Protective effect of acetylcysteine against thiamethoxam-induced hepatic and renal toxicity in rats

“…Thus it is considered an important antioxidant as it stimulates GSH synthesis, therefore maintaining intracellular GSH levels and scavenging ROS [20]. Also, NAC improves the viability of human hepatocytes and protects the liver [21] and kidneys [22] against oxidant damage. NAC has an ameliorative effect against many pesticides toxicity such as organophosphate compounds (Yurumez et al, 2007; [23][24][25], alpha-cypermethrin [26], carbamates [27], and imidacloprid [28].…”