Study summary · research use only
AICAR, an AMPK activator, protects against cisplatin-induced acute kidney injury through the JAK/STAT/SOCS pathway
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this rat study (Sprague-Dawley rats) with companion experiments in NRK-52E rat kidney cells, the authors examined whether the AMPK activator AICAR affects cisplatin-induced acute kidney injury (AKI) via the JAK/STAT/SOCS pathway. Rats were divided into control, AICAR, cisplatin (7 mg/kg), and cisplatin plus AICAR (100 mg/kg daily) groups; blood urea nitrogen, serum creatinine, and renal tissue markers (p-AMPK, Kim-1, cleaved caspase 3, JAK/STAT/SOCS) were measured. AICAR treatment was associated with reduced cisplatin-induced tubular injury markers and increased p-AMPK expression in NRK-52E cells, along with reduced JAK2/STAT1 protein expression and increased SOCS1. The authors describe these findings as indicating a mechanism involving the JAK2/STAT1/SOCS1 pathway and reduced apoptosis markers.
Abstract
Cisplatin causes acute kidney injury (AKI) through proximal tubular injury. We investigated the protective effect of the adenosine monophosphate protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) against cisplatin-induced AKI. We investigated whether the AMP-kinase activator AICAR ameliorates cisplatin-induced AKI through the JAK/STAT/SOCS pathway. Male Sprague-Dawley (SD) rats were randomly divided into four groups: control, AICAR, cisplatin, and cisplatin + AICAR. As appropriate to their treatment group, the rats were injected with a single dose of cisplatin (7 mg/kg, i.p.). AICAR was administered to the rats at 100 mg/kg i.p. daily. Blood urea nitrogen (BUN) and serum creatinine were measured. Renal damage was analyzed in sections stained with hematoxylin and eosin (H&E). Renal tissues were also examined by immunohistochemistry and western blot for p-AMPK, Kim-1, cleaved caspase 3, and JAK/STAT/SOCS. For in vitro studies, NRK-52E normal rat kidney cells were treated with cisplatin and/or AICAR. By western blot, we confirmed the expression of p-AMPK and the JAK/STAT/SOCS pathway in NRK-52E cells. AICAR was protective against cisplatin-induced acute tubular injury by up-regulating p-AMPK expression in NRK-52E cells. Protein expression levels of JAK2/STAT1 were markedly ameliorated in NRK-52E cells by AICAR. The protective mechanism of AICAR may be associated with suppression of the JAK2/STAT1 pathway and up-regulation of SOCS1, an inhibitor of the JAK2/STAT1 pathway. The present study demonstrates the protective effects of AICAR against cisplatin-induced AKI and shows a new renoprotective mechanism through the JAK2/STAT1/SOCS1 pathway and apoptosis inhibition. This study suggests that activation of the AMPK activator AICAR might ameliorate cisplatin-induced AKI.
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