NLRP3 Inflammasome Modulation by Melatonin Supplementation in Chronic Pristane-Induced Lupus Nephritis

Int J Mol Sci. 2019 Jul 15;20(14):3466. doi: 10.3390/ijms20143466.


Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation.

Keywords: Lupus nephritis; inflammation; melatonin; oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Female
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / etiology
  • Lupus Nephritis / metabolism
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Terpenes / toxicity


  • Anti-Inflammatory Agents
  • Antioxidants
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Terpenes
  • pristane
  • Melatonin