Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats

Author(s)

Shimizu, Maria Heloisa Massola ; Volpini, Rildo Aparecido ; de Braganca, Ana Carolina ; Nascimento, Mariana Moura ; Bernardo, Desiree Rita Denelle ; Seguro, Antonio Carlos ; Canale, Daniele

• Document type: Journal article
• Source: PLoS One; v. 18, n. 2, p. 19-pg., 2023-02-16.

Abstract

Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3 beta (GSK3 beta) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibrosis. Treatment with a single dose of lithium, an inhibitor of GSK3 beta, accelerated recovery of renal function in cisplatin and ischemic/reperfusion-induced AKI models. We aimed to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI. Male Wistar rats were allocated to four groups: Sham, received saline 0.9% intraperitoneally (IP); lithium (Li), received a single IP injection of lithium chloride (LiCl) 80 mg/kg body weight (BW); glycerol (Gly), received a single dose of glycerol 50% 5 mL/kg BW intramuscular (IM); glycerol plus lithium (Gly+Li), received a single dose of glycerol 50% IM plus LiCl IP injected 2 hours after glycerol administration. After 24 hours, we performed inulin clearance experiments and collected blood / kidney / muscle samples. Gly rats exhibited renal function impairment accompanied by kidney injury, inflammation and alterations in signaling pathways for apoptosis and redox state balance. Gly+Li rats showed a remarkable improvement in renal function as well as kidney injury score, diminished CPK levels and an overstated decrease of renal and muscle GSK3 beta protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NF kappa B and caspase renal protein expression and increased the antioxidant component MnSOD. Lithium treatment attenuated renal dysfunction in rhabdomyolysis-associated AKI by improving inulin clearance and reducing CPK levels, inflammation, apoptosis and oxidative stress. These therapeutic effects were due to the inhibition of GSK3 beta and possibly associated with a decrease in muscle injury. (AU)

• FAPESP's process: 15/11933-3 - ANTIOXIDANT AND RENOPROTECTIVE EFFECTS OF ALLOPURINOL ON RHABDOMYOLYSIS SECONDARY TO GLYCEROL, STATINS, BOTHROPS VENOM AND LEPTOSPIROSIS
• Grantee: Antonio Carlos Seguro
• Support Opportunities: Regular Research Grants