Venenum Bufonis induces rat neuroinflammation by activiating NF-κB pathway and attenuation of BDNF

Abstract

Ethnopharmacological relevance: Venenum Bufonis (VB), also called toad venom, has been widely used in clinic as a cardiotonic, anohyne and antineoplastic agents both in China and other Asian countries. However, its neurotoxicity and cardiotoxicity limit its wide clinical application. Compared with extensive attention attracted with cardiotoxicity, the toxic effect of VB on Central Nervous System (CNS) is much less studied.

Aim of the research: This study was performed to examine the neurotoxicity caused by VB on Sprague Dawley (SD) rats, then to clarify the mechanism in vivo by investigating its action on the neuroinflammation which possibly attributed to the activation of nuclear factor κB (NF-κB) pathway and the attenuation of brain-derived neurotrophic factor (BDNF).

Materials and methods: Rats administrated with 0.5% carboxymethyl cellulose sodium salt (CMC-Na) aqueous solution and VB (100mg/kg, 200mg/kg and 400mg/kg) were sacrificed at 2h, 4h, 6h, 8h, 24h and 48h. The brain level of neurotransmitters and their corresponding receptors, pro-inflammatory cytokines, BDNF/TrkB and NF-κB pathway-related proteins were examined, respectively.

Results: VB administration induced severe neurologic damage and neuroinflammation, as indicated by the disordered 5-hydroxytryptamine (5-HT), dopamine (DA) and their corresponding receptors, together with the over production of inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). VB also notably promoted the expression of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ and down-regulated the expression of BDNF and TrkB.

Conclusion: This study demonstrates that VB triggers neurotoxicity which probably is induced by neuroinflammation via activating of NF-κB pathway and attenuating the expression of BDNF.

Keywords: Arenobufagin (PubChem CID: 12305198); Brain-derived neurotrophic factor (BDNF); Bufalin (PubChem CID: 9547215); Bufotalin (PubChem CID: 259578); Cinobufagin (PubChem CID: 11969541); Cinobufotalin (PubChem CID: 259776); Desacetylbufotalin (PubChem CID: 12358889); Hellebrigenin (PubChem CID: 259577); Inflammation; NF-B pathway; Neurotoxicity; Resibufogenin (PubChem CID: 6917974); Telocinobufagin (PubChem CID: 259991); Venenum Bufonis.