Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jul 2014
α-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat model of sepsis.
Acute kidney injury is a frequent and serious complication in patients with severe sepsis. α-Lipoic acid (ALA), a naturally occurring dithiol compound, has been shown to possess anti-inflammatory and anti-oxidative properties. In the present study we investigated whether ALA could attenuate acute kidney injury and improve survival in a rat model of sepsis. Rats were subjected to caecal ligation and puncture (CLP) to induce sepsis. α-Lipoic acid (200 mg/kg) was administered by oral gavage either immediately (early treatment) or 12 h after the surgical procedure (delayed treatment). ⋯ Furthermore, early treatment with ALA markedly inhibited the release of tumour necrosis factor-α, interleukin (IL)-6 and IL-1β into the serum and reduced mRNA and protein expression of inducible nitric oxide synthase and high mobility group box 1 in kidney tissues from CLP-induced rats. Finally, CLP-induced nuclear factor-κB activation in kidney tissues was significantly suppressed by early ALA treatment. Together, the results indicate that ALA is able to reduce mortality and attenuate acute kidney injury associated with sepsis, possibly by anti-inflammatory actions. α-Lipoic acid may be a promising novel agent for the treatment of conditions associated with septic shock.