Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and protection from it by Brazilian propolis and artepillin C

Abstract

In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA) in male ddY mice, primary pulmonary cancers were also induced in bronchiolar and alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), products of oxidative processes, increased in bronchiolar and alveolar cells after administration of Fe-NTA. These substances disappeared after oral administration of propolis or artepillin C, as shown histochemically, and correlated with an anticancer prophylactic effect of propolis and artepillin C. From our investigation, lipid peroxidation seems to play an important role in pulmonary carcinogenesis. Malignant progression from adenoma of bronchiolar or alveolar origin to malignant tumors has been proposed to involve a stepwise transformation. In our study, adenomas developed into adenocarcinomas and large cell carcinomas after treatment with Fe-NTA. In contrast, after oral administration of propolis or artepillin C, adenomas did not progress to carcinomas. Instead of developing into large cell cancers, as induced by Fe-NTA in control mice, adenomas showed remarkable proliferation of macrophages and local anti-oxidant activity after treatment with either propolis or artepillin C. Propolis and artepillin C therefore appear to inhibit lipid peroxidation and the development of pulmonary cancers.

Translocation Pathway of the Intratracheally Instilled Ultrafine Particles from the Lung into the Blood Circulation in the Mouse

“…Thereafter the sections were reacted with primary antibody for 20 minutes with MW treatment. The peroxidase-conjugated goat anti-rabbit IgG diluted at 1:400 (DAKO, Glostrup, Denmark) was reacted to sections for 7minutes with MW treatment as a secondary antibody (Kimoto et al, 2001). The positive reactions resulted in brown staining with a DAB-H 2 O 2 solution [0.02% (w/v) 3, 3 -diaminobenzidine tetrahydrochloride (DAB) and 0.01% (v/v) H 2 O 2 in 0.05 M Tris-HCl buffer, pH 7.6] for 30 minutes, and the sections were counterstained with hematoxylin.…”

Supercritical CO2 extraction of raw propolis and its dry ethanolic extract

“…Propolis has been used in folk medicine for many years, especially in Europe and Japan, due to the variety of its therapeutic activities (Chen et al, 2009) including antibacterial (Kujumgiev et al, 1999), antifungal (Valdés et al, 1987), antiviral (Amoros et al, 1994), anticancer (Matsuno, 1995) (Kimoto et al, 2001), immunomodulation (Dimov et al, 1992) and antiinflammatory activities (Dobrowolski et al, 1991), among others. These activities are associated with the phenolic constituents, especially flavonoids and phenolic acids (Funari and Ferro, 2006).…”

Chemoprevention with green propolis green propolis extracted in L-lysine versus carcinogenesis promotion with L-lysine in N-Butyl-N-[4-hydroxybutyl] nitrosamine (BBN) induced rat bladder cancer

“…The alcoholic extract of green propolis containing artepillin C and synthetic artepillin C reduced lung carcinogenesis in mice 8 This indicates that other compounds were responsible for the decrease in the incidence of carcinogenesis in Group I. Is this an antioxidant or immunomodulatory effect?…”

“…Among the most promising is the anticarcinogenic action of its constituents, some of which have been tested in laboratory animals and human cell culture [8][9][10] .…”