Back to Search
Start Over
Dimethyl ester of bilirubin ameliorates Naja naja snake venom-induced lung toxicity in mice via inhibiting NLRP3 inflammasome and MAPKs activation.
- Source :
-
Toxicon : official journal of the International Society on Toxinology [Toxicon] 2024 Jun; Vol. 244, pp. 107757. Date of Electronic Publication: 2024 May 11. - Publication Year :
- 2024
-
Abstract
- Naja naja snake bite causes thousands of deaths worldwide in a year. N. naja envenomed victims exhibit both local and systemic reactions that potentially lead to death. In clinical practice, pulmonary complications in N. naja envenomation are commonly encountered. However, the molecular mechanisms underlying N. naja venom-induced lung toxicity remain unknown. Here, we reasoned that N. naja venom-induced lung toxicity is prompted by NLRP3 inflammasome and MAPKs activation in mice. Treatment with dimethyl ester of bilirubin (BD1), significantly inhibited the N. naja venom-induced activation of NLRP3 inflammasome and MAPKs both in vivo and in vitro (p < 0.05). Further, BD1 reduced N. naja venom-induced recruitment of inflammatory cells, and hemorrhage in the lung toxicity examined by histopathology. BD1 also diminished N. naja venom-induced local toxicities in paw edema and myotoxicity in mice. Furthermore, BD1 was able to enhance the survival time against N. naja venom-induced mortality in mice. In conclusion, the present data showed that BD1 alleviated N. naja venom-induced lung toxicity by inhibiting NLRP3 inflammasome and MAPKs activation. Small molecule inhibitors that intervene in venom-induced toxicities may have therapeutic applications complementing anti-snake venom.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Mice
Bilirubin
Snake Bites drug therapy
Lung drug effects
Lung pathology
Mitogen-Activated Protein Kinases metabolism
Male
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors
Elapid Venoms toxicity
Inflammasomes
Naja naja
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3150
- Volume :
- 244
- Database :
- MEDLINE
- Journal :
- Toxicon : official journal of the International Society on Toxinology
- Publication Type :
- Academic Journal
- Accession number :
- 38740099
- Full Text :
- https://doi.org/10.1016/j.toxicon.2024.107757