Snake Venom and a Phospholipase A Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators.

Viper snake (Cdr) is a subspecies found in northern area of Brazil. Among the snakes of genus subspecies, the venom of Cdr presents highest level of crotoxin, which is the major component of snake venoms, formed by two subunits (crotapotin and a phospholipase A named CBr) and presents potent neurotoxic activity. Curiously, the venom of (CdrV) is better neutralized by antibothropic than by anticrotalic serum, strongly suggesting that this venom has similarities with venom of genus snakes with regard to the ability to induce inflammation.

A Snake Venom-Secreted Phospholipase A Induces Foam Cell Formation Depending on the Activation of Factors Involved in Lipid Homeostasis.

MT-III, a snake venom GIIA sPLA, which shares structural and functional features with mammalian GIIA sPLAs, activates macrophage defense functions including lipid droplet (LDs) formation, organelle involved in both lipid metabolism and inflammatory processes. Macrophages (Ms) loaded with LDs, termed foam cells, characterize early blood vessel fatty-streak lesions during atherosclerosis. However, the factors involved in foam cell formation induced by a GIIA sPLA are still unknown.

A snake venom group IIA PLA with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ in macrophages.

Crotoxin B (CB) is a catalytically active group IIA sPLA from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLAs, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators.

Critical role of TLR2 and MyD88 for functional response of macrophages to a group IIA-secreted phospholipase A2 from snake venom.

The snake venom MT-III is a group IIA secreted phospholipase A2 (sPLA2) enzyme with functional and structural similarities with mammalian pro-inflammatory sPLA2s of the same group. Previously, we demonstrated that MT-III directly activates the innate inflammatory response of macrophages, including release of inflammatory mediators and formation of lipid droplets (LDs). However, the mechanisms coordinating these processes remain unclear.

Pharmacological evaluation and preliminary pharmacokinetics studies of a new diclofenac prodrug without gastric ulceration effect.

Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect.