Paricalcitol Ameliorates Acute Kidney Injury in Mice by Suppressing Oxidative Stress and Inflammation via Nrf2/HO-1 Signaling.

Abstract

Effective and targeted prevention and treatment methods for acute kidney injury (AKI), a common clinical complication, still needs to be explored. Paricalcitol is a biologically active chemical that binds to vitamin D receptors in the body to exert anti-oxidant and anti-inflammatory effects. However, the molecular mechanism of the effect of paricalcitol on AKI remains unclear. The current study uses a paricalcitol pretreatment with a mouse AKI model induced by cisplatin to detect changes in renal function, pathology and ultrastructure. Results showed that paricalcitol significantly improved renal function in mice and reduced inflammatory cell infiltration and mitochondrial damage in renal tissue. Furthermore, paricalcitol markedly suppressed reactive oxygen species and malondialdehyde levels in the kidneys of AKI mice and increased the levels of glutathione, superoxide dismutase, Catalase and total anti-oxidant capacity. In addition, we detected renal necrosis and inflammation-related proteins in AKI mice by immunofluorescence and Western blot, and found that their levels were markedly decreased after paricalcitol pretreatment. Moreover, paricalcitol promotes nuclear factor erythroid 2-related factor 2 (Nrf2) in the nucleus and activates the Nrf2/heme oxygenase-1 (HO-1) signaling pathway; while HO-1 is inhibited, the protective effect of paricalcitol on the kidney is attenuated. In conclusion, paricalcitol exerts a renoprotective effect by decreasing renal oxidative injury and inflammation through Nrf2/HO-1 signaling, providing a new insight into AKI prevention.

• Authors: Shuang Wang, Siqi Huang, Xingyao Liu, Yanjun He, Yun Liu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 2 (Jan 04 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36674485 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• NF-E2-Related Factor 2
• paricalcitol
• Heme Oxygenase-1

Topics

• Mice
• Animals
• Antioxidants (pharmacology)
• NF-E2-Related Factor 2 (metabolism)
• Heme Oxygenase-1 (metabolism)
• Oxidative Stress
• Signal Transduction
• Acute Kidney Injury (metabolism)
• Kidney (metabolism)
• Inflammation (metabolism)