Crotalus durissus terrificus snake venom activates 3T3-L1 preadipocytes to release PGE₂, which depends on COX-2 expression and is modulated by PGE₂ EP2 receptor

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Snakebites are a worldwide public health problem with high-cost treatment in many countries. Crotalus genus snakes, commonly known as rattlesnakes, cause the most lethal snakebites in Brazil. Crotalus ssp envenomation is characterised by systemic neurotoxicity, myotoxicity, renal failure and minor local effects. Despite the knowledge of envenomation's pathogenesis, the impact of Crotalus venom on adipose tissue (AT) cells is unknown. AT is an endocrine organ capable of releasing diverse immunomodulatory molecules, including prostaglandin E 2 (PGE 2 ). Herein, we investigated the effects of Crotalus durissus terrificus venom (CdtV) on preadipocytes in vitro, focussing on the release of PGE 2 and mechanisms involved. CdtV (5 and 10 μg/mL) induced a marked release of PGE 2 by preadipocytes (3-24 h) compared to controls. Pre-treatment of cells with SC-560 or NS-398, selective inhibitors for cyclooxygenase (COX)-1 and COX-2 enzymes, respectively, decreased CdtV-induced PGE 2 release after 24 h. CdtV (1 and 10 μg/mL) did not change COX-1 protein expression by preadipocytes, but induced COX-2 protein expression at all time intervals evaluated. Pre-treating preadipocytes with AH6809, an inhibitor of the PGE 2 EP2 receptor, significantly increased the CdtV-induced PGE 2 release. EP1, EP3, or EP4 receptor antagonists did not change the CdtV-induced PGE 2 release. Additionally, CdtV did n

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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