Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats
Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3β (GSK3β) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibro...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934413/?tool=EBI |
| _version_ | 1797903290764099584 |
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| author | Maria Heloisa Massola Shimizu Rildo Aparecido Volpini Ana Carolina de Bragança Mariana Moura Nascimento Desiree Rita Denelle Bernardo Antonio Carlos Seguro Daniele Canale |
| author_facet | Maria Heloisa Massola Shimizu Rildo Aparecido Volpini Ana Carolina de Bragança Mariana Moura Nascimento Desiree Rita Denelle Bernardo Antonio Carlos Seguro Daniele Canale |
| author_sort | Maria Heloisa Massola Shimizu |
| collection | DOAJ |
| description | Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3β (GSK3β) 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 GSK3β, 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 GSK3β protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NFκB 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 GSK3β and possibly associated with a decrease in muscle injury. |
| first_indexed | 2024-04-10T09:30:33Z |
| format | Article |
| id | doaj.art-111ad5e8be3a41ccb42388f08fea3ac4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T09:30:33Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-111ad5e8be3a41ccb42388f08fea3ac42023-02-19T05:31:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01182Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in ratsMaria Heloisa Massola ShimizuRildo Aparecido VolpiniAna Carolina de BragançaMariana Moura NascimentoDesiree Rita Denelle BernardoAntonio Carlos SeguroDaniele CanaleRhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3β (GSK3β) 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 GSK3β, 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 GSK3β protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NFκB 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 GSK3β and possibly associated with a decrease in muscle injury.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934413/?tool=EBI |
| spellingShingle | Maria Heloisa Massola Shimizu Rildo Aparecido Volpini Ana Carolina de Bragança Mariana Moura Nascimento Desiree Rita Denelle Bernardo Antonio Carlos Seguro Daniele Canale Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats PLoS ONE |
| title | Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats |
| title_full | Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats |
| title_fullStr | Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats |
| title_full_unstemmed | Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats |
| title_short | Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats |
| title_sort | administration of a single dose of lithium ameliorates rhabdomyolysis associated acute kidney injury in rats |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934413/?tool=EBI |
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