Cristiani Baldo

Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice

Jararhagin is a hemorrhagic metalloprotease from Bothrops jararaca snake venom. The hyperalgesic mechanisms of jararhagin were investigated focusing on the role of proinflammatory cytokines (TNF-α and IL-1β) and the transcription factor NFκB. Intraplantar administration of jararhagin (1, 10, 100 and 1000 ng/paw) induced mechanical hyperalgesia, and increased TNF-α levels at 1, 3 and 5 h, and IL-1β levels at 0.5, 1 and 3 h after its injection in the paw tissue. Pre-treatment with morphine (2, 6, 12 μg/paw) inhibited jararhagin-induced mechanical hyperagesia. The systemic or local pre-treatment with etanercept (10 mg/kg and 100 μg/paw) and IL-1ra (30 mg/kg and 100 pg/paw) inhibited jararhagin-induced mechanical hyperalgesia. Co-administration of jararhagin (0.1 ng/paw) and TNF-α (0.1 pg/paw) or jararhagin (0.1 ng/paw) and IL-1β (1 pg/paw) enhanced the mechanical hyperalgesia. The systemic or local pre-treatment with PDTC (NFκB inhibitor; 100 mg/kg and 100 μg/paw) inhibited jararhagin-induced mechanical hyperalgesia as well as PDTC decreased the jararhagin-induced production of TNF-α and IL-1β. Thus, these data demonstrate the involvement of pro-inflammatory cytokines TNF-α and IL-1β and nuclear transcription factor NFκB in jararhagin-induced mechanical hyperalgesia indicating that targeting these mechanisms might contribute to reduce the pain induced by B. jararaca snake venom.

Study of lipase production by a filamentous fungus isolated from soil contaminated with lipid residues

(ANOVA) showed significant effects when temperature and oil concentration varied. The maximum level of lipase production (206.68U/ml) was reached with 0.5%(W/V) of olive oil, 1.5%(W/V) of ammonium nitrate and at the temperature of 24°C. Lipase production is generally stimulated by lipids and is usually coordinated with the availability of triglycerides. Furthermore, nitrogen sources in the medium have to be carefully considered for growth and optimization of production. Response surface methodology has been widely used to bring insights of the interaction effects of several process parameters, generally resulting in higher production yields. In this work, with the evaluated levels of each tested parameter, we did not achieve an optimized condition. Further experiments are needed in order to get an optimized process of lipase production. Nevertheless, the soil-isolated filamentous fungi demonstrated an interesting ability to produce lipase in both solid-state and submerged fermentation.