ABSTRACT
BACKGROUND: Macrophages play central roles in homeostasis as well as host defence in innate and acquired immunity, auto-immunity and immunopathology. Our research group has demonstrated the effects of highly diluted toxic substances in macrophages. AIM: To investigate if highly diluted Mercurius solubilis (Merc sol), can activate or modulate macrophage functions. METHODS: We evaluated the effects of Merc sol in the 6, 12, 30 and 200 centesimal high dilutions (CH) potencies on mice peritoneal macrophages (in vitro and in vivo). Merc sol was added to mice's drinking water for 7 days (in vivo treatment) and animals were euthanised and cells were collected. In vitro treatment was performed on macrophages and bone-marrow cell cultures. RESULTS: Macrophages showed activated morphology, both when Merc sol was added directly to the cell culture and to drinking water. The in vitro experiments showed enhanced morphological activation, increased interferon (IFN)γ release in the supernatant at lower dilutions and interleukin (IL)-4 production at higher dilutions. Increase in nitric oxide and decrease in superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) were also observed. In vivo treatment caused a decrease in O(2)(-) and increase in H(2)O(2) production by macrophages. DISCUSSION: Taken together, the results allow us to conclude that highly diluted Merc sol modulates reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokine secretion, which are central mediators of the immune system, wound healing and body homeostasis.
Subject(s)
Macrophages, Peritoneal/drug effects , Mercury Compounds/pharmacology , Animals , Homeopathy , Interferons/metabolism , Interleukin-4/metabolism , Macrophages, Peritoneal/metabolism , Male , Mercury Compounds/chemistry , Mice , Reactive Oxygen Species/metabolism , Solutions , Superoxides/metabolismABSTRACT
Background: Cancer is a class of disease responsible for 13% of death cause worldwide. Among all types of cancers, one of the most aggressive and with the highest death rate is melanoma. It is highly metastatic and current treatments with chemotherapeutic drugs do not yield satisfactory results. Therefore, the interest on new therapeutics for cancer treatment has been increasing on research. Highly diluted tinctures (HDT) are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Previous results have demonstrated in vitro inhibition of invasion ability and in vivo anti-metastatic potential of B16F10 lung metastasis model after mice treatment with M8 inhalation.Conclusion: Even though further investigation are necessary to elucidate the mechanisms of action of M8 treatment there is an indication that these highly diluted tinctures could be a promising therapy to treat metastatic melanoma.(AU)
Introdução: O Câncer é uma classe de doenças responsáveis por 13% das causas de mortes no mundo todo. Entre todos os tipos de cânceres, um dos mais agressivos e com maior índice de mortalidade é o melanoma. Ele é altamente metastático, e os tratamentos atuais com drogas quimioterapeuticas não geram resultados satisfatórios. Portanto, o interesse em novos agentes terapeuticos para o tratamento do câncer tem aumentado na pesquisa. Soluções altamente diluídas (CAD) são destinadas à aumentar a resposta do sistema imunológico resultando em menores frequencias de várias doenças, e também não apresentam riscos de graves efeitos colaterais, devido à sua toxicidade reduzida. Resultados anteriores demostraram a inibição in vitro da habilidade de invasão e potencial antimetastático in vivo do modelo de metástase pulmonar da B16F10, após o tratamento dos camundongos pela inalação do M8.Conclusão: Mais pesquisas são necessárias para esclarecer os mecanismos de ação do tratamento com M8. Entretanto, há um indicativo de que soluções altamente diluídas podem ser terapias coadjuvantes para o tratamento do melanoma metastático.(AU)
Subject(s)
Animals , Mice , Melanoma/therapy , Hyaluronic Acid , Hyaluronan Receptors , High PotenciesABSTRACT
BACKGROUND: Kinins are released during dermal injury and inflammation and seem to contribute to the pathogenesis of cutaneous diseases. OBJECTIVE: Participation of kinins in skin inflammatory process was evaluated using knockout mice and non-peptide kinin receptor antagonists. METHODS: Chronic skin inflammation was induced by multiple applications of TPA in mice ear. RESULTS: The B(2) knockout mice (B(2)(-/-)) showed a significant increase of ear weight (23 ± 10%) and epidermal cellular hyperproliferation and acanthosis formation upon histological analysis when compared with wildtype mice. Also, evaluation of PCNA levels by Western blot and immunohistochemistry confirmed the increase in the epidermis hyperproliferation in the ear skin of B(2)(-/-) mice. In contrast, no modification in these parameters was detected in B(1) knockout mice (B(1)(-/-)). However, mice lacking both kinin receptors (B(1)B(2)(-/-)) presented a considerable reduction of epidermis thickness and in PCNA levels. Following the establishment of skin inflammation (5th day of TPA application) treatment with the non-peptide antagonists SSR 240612 (B(1) receptor antagonist), FR 173657 (B(2) receptor antagonist), or SSR 240612 plus FR 173657 topically applied, caused a significant inhibition of ear weight (20 ± 5%, 34 ± 4% and 32 ± 6%, respectively). In the histological analysis, the antagonists produced a reduction in epidermal hyperplasia and acanthosis formation; but the treatment with a combination of the two antagonists did not increase efficacy. CONCLUSION: Kinin receptors seem to be involved in the control of the keratinocyte hyperproliferative process, and non-peptide kinin receptor antagonists may be useful tools in the treatment of hyperproliferative skin disorders.
