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Renoprotective Effects of Xenon on Lupus Nephritis: Inhibition of NLRP3 Inflammasome and Oxidative Stress

This study investigates the renoprotective effects of xenon on lupus nephritis, a severe form of renal inflammation and fibrosis. The results demonstrate that xenon inhibits the activation of NLRP3 inflammasome and oxidative stress, leading to reduced albuminuria, improved renal function, and histopathological improvement. Mechanistic studies suggest that xenon's renoprotective effects involve the suppression of NF-kB/NLRP3 inflammasome pathways and apoptosis-related signal pathways, as well as the activation of antioxidant signaling.

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Renoprotective Effects of Xenon on Lupus Nephritis: Inhibition of NLRP3 Inflammasome and Oxidative Stress

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  1. Renoprotective effects of xenon on lupus nephritis by inhibiting NLRP3 inflammasome and oxidative stress Shuk-Man Ka, PhD Associate Professor Academy of Medicine, National Defense Medical Center, Taipei, Taiwan Orlando USA Sep 29 2016

  2. Accelerated and severe lupus nephritis Accelerated and severe lupus nephritis (ASLN) features acute onset of severe clinical manifestations andhistopathological renal lesions, may represent a severe form of renal inflammation and fibrosis, with relatively high possibility of progressing to uremia and the patients require dialysis treatment or renal transplantation. (A representative case from Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan)

  3. WHO classification of lupus nephritis

  4. . Current treatment for ASLN The current therapy for ASLN is to the mainly use corticosteroids or combined corticosteroids with other cytotoxic agents or immunomodulators (such as cyclophosphamide, azathioprine or cyclosporine), although many of them are found to have severe systemic side effects. • Cyclosphosphamide • Chlorambucil • Mycophenolate mofetil • NSAIDs • ACE inhibitors Molino C et al., Eur J Intern Med, 20: 447-453, 2009; Yee CS et al., Ann Rheum Dis, 63: 525-529, 2004; Benseler SM et al., Rheumatology (Oxford), 48: 176-182, 2009.

  5. Xenon(Xe) • Xe is a colorless, dense, odorless noble gas found in the Earth's atmosphere in trace amounts. • Xe triggers pro-inflammatory effects and suppresses the anti-inflammatory response compared to sevoflurane in patients undergoing cardiac surgery. • Xe has been described as a renaprotectant in models of renal transplantation and acute kidney. Mervyn Maze and MBChB, Can J Anesth, 2015 Breuer et al., Critical Care ,2015

  6. Albuminuria and renal function

  7. Renal pathology ASLN+ Xe Control ASLN

  8. Renal T cell and macrophage infiltration ASLN+ Xe Control ASLN F4/80 CD3

  9. Renal dendritic cells infiltration ASLN+ Xe Control ASLN DCs CD11b

  10. Serum proinflammatory cytokines

  11. Renal and urinary ROS In situ renalROS ** * Kidney superoxide anion (RLU/15 min/mg) Control ASLN ASLN+Xe * * * ** Renal Nrf2 activity Renal HO-1 (ng/ml) (OD/mg nuclear protein) Control ASLN ASLN+Xe Control ASLN ASLN+Xe

  12. Renal NF-kB signal pathway p-NF-κB p65 ICAM-1 β-actin ** * Renal p-NF-kB activity (OD/mg protein) Control ASLN ASLN+Xe

  13. NF-kB signal pathways in primary mesangial cells Xe - - - - + + + LPS (mins) 0 30 60 360 30 60 360 ICAM-1 p-p-38 β-actin p-NF-κB p65 Lamin A

  14. Renal apoptosis (A) BAX Bcl-2

  15. Mitochondria injury in primary mesangial cells Con LPS+ATP+Xe LPS+ATP (A) (B) * R2: 93.07% R3: 4.68% R2: 87.45% R3: 9.31% R2: 93.22% R3: 4.68% * Xe - - + + LPS - + - + (C)

  16. Conclusion Xe inhibited the development of ASLN, as demonstrated by reduced albuminuria, improved renal function, and improved renal histopathology. Mechanistic studies showed that inhibition of the activation of NF-kB/NLRP3 inflammasome pathways and apoptosis-related signal pathways, and antioxidant signaling were involved in the major mechanisms of action for the renoprotective effects of Xe.

  17. Sky lantern festival, Taipei Thank you very much

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