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

2. Accelerated and severe lupus nephritis
Accelerated and severe lupus nephritis (ASLN) features acute onset of severe clinical manifestations and histopathological 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.
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: , 2009; Yee CS et al., Ann Rheum Dis, 63: , 2004; Benseler SM et al., Rheumatology (Oxford), 48: , 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

7. Albuminuria and renal function

8. Renal pathology
Control
ASLN
ASLN+ Xe

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

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

11. Serum proinflammatory cytokines

12. Renal and urinary ROS Renal HO-1 (ng/ml) Renal Nrf2 activity
In situ renal ROS ** *
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

13. 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

14. NF-kB signal pathways in primary mesangial cellsXe
LPS (mins)
ICAM-1
p-p-38
β-actin
p-NF-κB p65
Lamin A

15. Renal apoptosis
(A)
BAX
Bcl-2

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

17. 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.

18. Sky lantern festival, Taipei
Thank you very much