RESUMO
The pathophysiological responses to immune stress (IS) include activation of several processes which are dependent on cytosolic Ca2+ elevation. Magnesium frequently acts as a natural Ca2+ antagonist. In this study we have observed that Mg2+ can protect guinea-pigs against IS. Antigen-sensitized guinea-pigs, which had been fed a magnesium-deficient diet, were given a single dose (15 mg) of MgCl2 intraperitoneally 1 h before antigen challenge. The development of anaphylactic shock (AS) was observed during the next 2 h, and the hearts were subsequently examined histologically for signs of cardiac myolysis (CM). Magnesium (i) reduced the incidence of CM from 40% to 10% (p < 0.05); (ii) reduced the incidence of AS from 61% to 35% (p < 0.05); (iii) attenuated the severity of the AS; and (iv) lowered mortality from 39% in the control to 19% in the Mg(2+)-treated group (p = 0.1). Serum and tissue total [Mg2+] were not affected by the administration of MgCl2. Also, the serum and heart Mg2+ levels were the same whether or not the guinea-pigs developed AS or CM. In cell culture we demonstrated that by elevating the [Mg2+] in the medium bathing sensitized rat basophilic leukemia (RBL) cells, the increase in cytosolic [Ca2+] subsequent to antigen challenge was reduced from 174 +/- 23.28% (1 mM) to 82.74 +/- 13.22% (3 mM). We conclude that a single treatment with Mg2+ can considerably diminish damage induced by immune stress, probably by its altering the Ca2+: Mg2+ ratio. Since the physiological reaction to different types of stress is similar, Mg2+ could prove beneficial in preventing stress-induced shock in general. Studies examining the mechanisms by which Mg2+ exerts its effects thus provide a scientific basis for the current clinical use of Mg2+ in acute myocardial infarction (AMI) and asthma.
Assuntos
Anafilaxia/tratamento farmacológico , Cloreto de Magnésio/uso terapêutico , Miocárdio/patologia , Anafilaxia/complicações , Animais , Antígenos/administração & dosagem , Antígenos/toxicidade , Cálcio/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Modelos Animais de Doenças , Cobaias , Coração/efeitos dos fármacos , Injeções Intraperitoneais , Leucemia Basofílica Aguda/patologia , Magnésio/sangue , Magnésio/metabolismo , Cloreto de Magnésio/administração & dosagem , Cloreto de Magnésio/farmacologia , Deficiência de Magnésio/complicações , Deficiência de Magnésio/patologia , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Ratos , Organismos Livres de Patógenos Específicos , Células Tumorais CultivadasRESUMO
We examined whether protein kinases have a role in the expression of anaphylactic shock (AS). Guinea-pigs sensitized to ovalbumin were administered i.p. saline (control) or 10 micrograms/kg K252a, a potent protein kinase inhibitor, 30 min before challenge. The development of AS and mortality was observed for the next 2 h. In the K252a-treated group the incidence of AS fell to 53% from 100%, the maximum intensity was 62% less than the control, and mortality dropped to 16% from 50% of the animals. We suggest that protein kinases are involved in the expression of AS, and that inhibitors of these enzymes may protect against the symptoms of AS and allergy.
Assuntos
Anafilaxia/enzimologia , Carbazóis/farmacologia , Proteína Quinase C/metabolismo , Anafilaxia/prevenção & controle , Animais , Cobaias , Alcaloides Indólicos , Masculino , Fosforilação , Proteína Quinase C/antagonistas & inibidoresRESUMO
Actively sensitized guinea pigs were rendered Mg(2+)-deficient for 2-3 weeks and then subjected to immune stress. No differences could be seen between treated and control groups prior to immune challenge. 1-2 h after antigen challenge, 95% of the Mg(2+)-deficient animals were observed to be anaphylactic, i.e. apathetic, dyspneic, and they had a rapid pulse rate. Only 4% of the control animals showed signs of anaphylaxis. Serum magnesium concentration, [Mg2+], fell from 1.32 +/- 0.07 mM in control guinea pigs to 0.56 +/- 0.04 mM in those fed an Mg(2+)-deficient diet. Cardiomyolysis (CM) developed in 19% of the anaphylactic animals and in 3% of the controls. We conclude that Mg(2+)-deficient animals continue to function, provided conditions are normal, but they are unable to withstand stress. The heart, however, appears to be better equipped to defend itself against Mg2+ deficiency and low serum [Mg2+], a supposition supported by the fact that heart [Mg2+] is not significantly reduced in hypomagnesemic guinea pigs (0.864 +/- 0.021 microgram/mg dry weight in control, and 0.834 +/- 0.062 microgram/mg dry weight in magnesium-deficient animals). The data indicate that hypomagnesemia heightens the intensity of the immune response, thereby exacerbating both anaphylactic shock (AS) and CM. A normal serum [Mg2+] would thus seem essential for protection against immune stress.