RESUMO
To investigate the effects of metformin on angiogenesis, on inflammatory cell accumulation and on production of endogenous cytokines in sponge implant in mice. Polyester-polyurethane sponges were implanted in Swiss mice and metformin (40 or 400mg/kg/day) was given orally for six days. The implants collected at day 7 postimplantation were processed for the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) e collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Metformin treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of transforming growth factor (TGF-beta1) intraimplant. A regulatory function of metformin on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of metformin.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Reação a Corpo Estranho/tratamento farmacológico , Inflamação/prevenção & controle , Metformina/uso terapêutico , Neovascularização Patológica/prevenção & controle , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Quimiocina CCL2/biossíntese , Quimiocina CCL2/genética , Quimiotaxia de Leucócito/efeitos dos fármacos , Colágeno/biossíntese , Colágeno/genética , Avaliação Pré-Clínica de Medicamentos , Reação a Corpo Estranho/metabolismo , Reação a Corpo Estranho/fisiopatologia , Inflamação/fisiopatologia , Masculino , Metformina/farmacologia , Camundongos , Peroxidase/análise , Tampões de Gaze Cirúrgicos , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Trace metals are involved in the mechanisms of CNS excitability, including epilepsy. In this study, atomic absorption spectrophotometry was used to determine concentrations of Mg(2+), Cu(2+) and Zn(2+) in plasma (microg/ml) and hair (microg/g) samples. Differential profiles of trace metals were detected in rats displaying three different kinds of seizures, i.e. acute audiogenic seizures (generalized tonic-clonic type GTC) and audiogenic kindling (limbic type; LS) in Wistar Audiogenic Rats (WARs) and electroshock-induced seizures (ES) in Wistar non-epileptic rats (resistant). Significantly lower Zn(2+) concentrations were observed in the plasma of WARs (0.80+/-0.02) compared with resistants (0.89+/-0.03) in the basal (non-seizing) condition. After GTC, WARs showed lower Zn(2+) levels (0.64+/-0.12) while both Mg(2+) (12.56+/-1.51) and Cu(2+) (0.81+/-0.14) were higher than in non-seizing WARs. After ES-induced seizures only Mg(2+) changed, being higher than in the basal condition (11.78+/-2.25 and 8.90+/-0.95). In hair, basal levels of Mg(2+) and Cu(2+) (192.49+/-36.73 and 13.33+/-1.76) were higher whereas Zn(2+) (136.53+/-15.67) was lower in WARs than in resistants. WARs submitted to 0, 3 and 25 stimuli presented higher Mg(2+) concentrations as the number of stimuli increased. In animals receiving the same number of stimuli, Zn(2+) levels were higher for animals displaying GTC (151.09+/-5.53) than those displaying LS (128.07+/-8.51). In conclusion, seizure type (limbic or generalized tonic-clonic) and number of stimuli seem to be the determinant factors for changes in Zn(2+) and Mg(2+) levels, respectively.