ABSTRACT
Major gingival-periodontal changes according to age have been observed in both diabetic and non-diabetic rats. Male Wistar rats weighing 200-220 g were divided into two groups: 1) Nondiabetic (ND) and 2) Diabetic (D) by receiving an intraperitoneal (ip) dose of streptozotocin (STZ) (50 mg /kg). Animals from both groups (ND and D) were euthanized at 4, 8, 12, 17 y 25 weeks after treatment with saline solution or STZ. Glycemia values in ND rats were 5 to 6 mmol/L, while in D, glycemia increased progressively between weeks 4 and 25, with values ranging from 18. 3±2. 1 to 39. 3±2. 7 mmol/L. Oxidative stress differed significantly in gums of ND and D rats. ND: lipid peroxidation: Malondialdehyde (MDA): 8. 52±1. 2 to 15. 5±2(nmol/mgP); superoxide dismutase (SOD): 37. 1±4. 2 to 21. 2±1. 3 (U/100mgP); D: MDA 13. 1±1. 6 to 22. 9±2. 7 (nmol/L); superoxide dismutase (SOD): 17. 7±0. 8 to 9. ±0. 2 (U/100mgP). Vascular permeability (VP) and gingival edema (E) showed significant changes between ND and D rats from 4 to 25 weeks. ND: PV: 10±0. 2 to 16. 1±1. 3 (EB ug/g dry t); E: 0. 9±0. 1 to 4. 1±1. 3 ml; D: PV: 12±1. 2 to 24. 4±1. 6 (EB ug/g dry t); E: 2. 2±0. 2 to 8. 4±1. 3 ml. Aging produced progressive natural changes in oxidative stress, VP and gingival E. In diabetic animals, changes in oxidative stress, VP and gingival E were observed early and were progressively more significant than for ND. According to these results, non-diabetic gingival modifications develop naturally with age, while in aging associated to diabetic disease, hyperglycemia increases progressively and early.
Se han observados importantes cambios gingivo-periodontales en función de la edad tanto en ratas no diabéticas como en ratas diabéticas. Ratas machos Wistar de 200-220 g de peso corporal fueron separadas en dos grupos: 1) No diabéticas(ND) ; 2) Diabéticas (D), por haber recibido una dosis intraperitoneal (ip) de estreptozotocina (STZ) (50 mg íkg). Ambos grupos de ratas (ND y D) fueron sacrificados a las 4, 8, 12, 17 y 25 semanas de edad después del tratamiento con solución salina o con STZ. En ratas ND las los valores de glucemia fueron de 5 a 6 mmol/L, en tanto que en las D las glucemias se observaron progresivamente aumentadas entre las 4 y las 25 semanas con valores entre 18. 3±2. 1 a 39. 3±2. 7 mmol/L. El estrés oxidativo mostró diferencias significativas entre las encías de animales ND respecto a los D; ND: peroxidacion lipidica: Malondihaldeido (MDA): 8. 52±1. 2 a 15. 5±2(nmol/mgP);superoxido dismutasa (SOD):37. 1±4. 2 a 21. 2±1. 3 (U/100mgP); D : MDA 13. 1±1. 6 a 22. 9±2. 7 (nmol/L); Superoxidodismutasa :SOD 17. 7±0. 8 a 9. ±0. 2 (U/100mgP). La permeabilidad vascular(PV) y el edema(E) gingival mostraron cambios significativos entre las 4 y las 25 semanas de edad entre los animales ND respecto a los D : ND : PV: 10±0. 2 a 16. 1±1. 3 (EB ug/g t seco); E :0. 9±0. 1 a 4. 1±1. 3 ml; D: PV :12±1. 2 a 24. 4±1. 6 (EB ug/g t seco); E 2. 2_/- 0. 2 a 8. 4± 1. 3 ml. El envejecimiento produjo cambios progresivos naturales en el estrés oxidativo, PV y Egingival. En tanto que en el estado diabético los cambios del estrés oxidativo, PV y E gingival se observan temprano y fueron progresivamente más significativos comparados con los ND. De acuerdo a estos resultados las modificaciones gingivales no diabéticas se desarrollan naturalmente en función de la edad, en cambio en la senectud asociada con enfermedad diabética la hiperglucemia aumenta progresiva y tempranamente.
Subject(s)
Aging/physiology , Diabetes Mellitus/physiopathology , Gingiva/physiology , Animals , Gingiva/physiopathology , Male , Rats , Rats, WistarABSTRACT
The role of bradykinin B1 receptors on the oxidative stress as measured by the levels of Na+/K+ ATPase activity, malondialdehyde (MDA) and glutathione (GSH) in male Wistar rat optic nerve and visual cortex area 1 and 4weeks after STZ treatment was studied. Rats were divided into 4 groups (n=6-7): 1. Controls (non-diabetics); 2. Diabetics (65mg/kg streptozotocin, STZ); 3. Diabetics injected with B1 antagonist R-954 (2mg/Kg) during the last 3days of a one week period; 4. Diabetics injected with B1 antagonist R-954 (2mg/Kg) during the last 3days of a 4week period. The results showed that plasma glucose levels increased by up to 4 fold in diabetic rats 1 or 4weeks following the STZ treatment. R-954 treatment did significantly decrease blood glucose levels. Levels of MDA was increased in the plasma of the 1 and 4week diabetic animals whereas the GSH levels were decreased. Both markers returned to normal following R-954 treatment. Na+/K+ ATPase activity significantly decreased in the optic nerve and visual cortex of diabetic rats at 1 and 4weeks but returned to normal following R-954 treatment. MDA levels increased markedly at 1 and 4weeks compared with control levels in the optic nerve but slightly in the visual cortex and returned to control levels in both tissues following R-954 treatment. GSH levels decreased in both tissues at 1 and 4weeks compared with control levels. Following administration of the selective BKB1R antagonist R-954, the levels of GSH returned to normal in both tissues of the 1 and 4week diabetic animals. These results showed that the inducible BKB1 receptors are associated with the oxidative stress in the optic nerve and cortical visual area of diabetic rats and suggested that BKB1-R antagonist R-954 could have a beneficial role in the treatment of diabetic retinopathy.
Subject(s)
Bradykinin B1 Receptor Antagonists/pharmacology , Diabetes Mellitus, Experimental/metabolism , Optic Nerve/drug effects , Oxidative Stress/drug effects , Visual Cortex/drug effects , Animals , Bradykinin/analogs & derivatives , Bradykinin/pharmacology , Male , Optic Nerve/metabolism , Rats , Rats, Wistar , Visual Cortex/metabolismABSTRACT
Gingival overgrowth is an adverse side effect of cyclosporine A (CsA) in the treatment of transplanted patients. The purpose of this study was to evaluate the effects of CsA on new-onset diabetes mellitus and gingival overgrowth in rats, by measuring collagen, nitric oxide and microvascular permeability. Blood glucose level, collagen, nitric oxide level and vascular permeability were determined. Blood glucose level increased significantly from 6.5 +/- 0.9 for the control group to 15+/- 1.2, 17 +/- 1.2 and 21.6+/- 1.6 mM/L at 1, 4 or 8 weeks of CsA treatment, respectively. Collagen (ug HO Proline/mg p) increased significantly from 2.5+/- 0.5 for the control group to 4.2+/- 0.8, 5.9+/- 0.6 and 7.3 +/- 0.8 at 1, 4 or 8 weeks of CsA treatment, respectively. Vascular permeability was 10.3+/- 1.2 for the control group and 15+/-1; 17.2 +/- 1.3, and 22.1+/- 2.1 ug EB/g T; at 1, 4 or 8 weeks of CsA treatment, respectively. Nitric oxide level was 3.5 +/- .9 umol/mg P for the control group and 4+/- 0.2, 8.2+/- 0.9 and 11+/-1 for 1, 2 or 8 weeks of CsA treatment, respectively. These findings appear to indicate that the development of significant gingival changes induced by CsA is related to new-onset of diabetes mellitus during the immunosuppressive treatment.
La hiperplasia gingival es un efecto colateral adverso del tratamiento con ciclosporina A (CsA) en pacientes transplantados. El proposito de este estudio fue evaluar el efecto de CsA en el inicio de diabetes mellitus, la concentracion de colageno, y de oxido nitrico y la permeabilidad capilar gingival. El nivel de glucosa en sangre de los animales controles fue: 6.5+/- 0.9, en tanto que los tratados con CsA fue: 15+/-1.2; 17+/- 1.1 y 21.6+/- 1.6 mM/L a las 1, 4 y 8 semanas respectivamente. El colageno (ug OH prolina/mg p) mostro un aumento significativo en los animales tratados con CsA respecto de los controles: 2.5+/- 0.5; 4.2+/- 0.8; 5.9+/- 0.6; 7.3+/- 0.8 respectivamente a las 1,4 y 8 semanas de tratamiento. Los valores de permeabilidad capilar (ug AE/ g T) fueron: en los animales control 10.3+./- 1.2; en los animales tratados con CsA, a las 1, 4 y 8 semanas 15+/- 1.0; 17.2 +/- 1.3 y 22.1+/- 2.1 respectivamente. Los valores de oxido nitrico (umol/mg p) en los animales control: 3.5+/-0.9; y en los animales tratados con CsA 4+/- 0.2; 8.2+/- 0.9 y 11.2 +/- 1.0 respectivamente. Estos resultados parecen indicar que el desarrollo de los significativos cambios gingivales inducidos por la administracion de CsA esta relacionado con la hiperglucemia temprana que se asocia al tratamiento con inmunosupresores.
Subject(s)
Animals , Male , Rats , Cyclosporine/adverse effects , Gingival Overgrowth/chemically induced , Hyperglycemia/chemically induced , Immunosuppressive Agents/adverse effects , Time Factors , Blood Glucose/analysis , Blood Glucose/drug effects , Capillary Permeability/drug effects , Random Allocation , Collagen/analysis , Collagen/drug effects , Rats, Wistar , Diabetes Mellitus/chemically induced , Coloring Agents , Evans Blue , Gingiva/drug effects , Gingiva/pathology , Nitric Oxide/analysisABSTRACT
Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with many complications including nephropathy, retinopathy, neuropathy and hyperalgesia. Experimental evidence has shown that the bradykinin B1 receptor (BKB1-R) is involved in the development of type 1 diabetes and found to be upregulated alongside the disease. In the present study the effects of the selective BKB1-R antagonist the R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8) ]des-Arg(9)-BK and the BKB1-R agonist des Arg(9)-BK (DBK) were studied on diabetic hyperglycemia. Diabetic type 1 was induced in C57 BL/KsJ mdb male mice by five consecutives doses of STZ (45mg/kg i.p.). A glucose tolerance test (GTT) was performed by an intraperitoneal administration of glucose, 8, 12 and 18days after the diabetes induction. The induction of type 1 diabetes provoked a significant hyperglycemia levels in diabetic mice at 12 and 18days after STZ. The administration of R-954 (400microg/kg i.p.) at 12 and 18days after STZ returned the glycemia levels of this animals to normal values. In addition the administration of DKB (300microg/kg i.p.) significantly potentiated the diabetes-induced hyperglycemia; this effect that was totally reversed by R-954. These results provide further evidence for the implication of BKB1-R in the type 1 diabetes mellitus (insulitis).
Subject(s)
Blood Glucose/drug effects , Bradykinin B1 Receptor Antagonists , Bradykinin/analogs & derivatives , Diabetes Mellitus, Experimental/drug therapy , Glucose Tolerance Test , Analysis of Variance , Animals , Bradykinin/pharmacology , Male , MiceABSTRACT
Gingival overgrowth is an adverse side effect of cyclosporine A (CsA) in the treatment of transplanted patients. The purpose of this study was to evaluate the effects of CsA on new-onset diabetes mellitus and gingival overgrowth in rats, by measuring collagen, nitric oxide and microvascular permeability. Blood glucose level, collagen, nitric oxide level and vascular permeability were determined. Blood glucose level increased significantly from 6.5 +/- 0.9 for the control group to 15 +/- 1.2, 17 +/- 1.2 and 21.6 +/- 1.6 mM/L at 1, 4 or 8 weeks of CsA treatment, respectively. Collagen (ug HO Proline/mg p) increased significantly from 2.5 +/- 0.5 for the control group to 4.2 +/- 0.8, 5.9 +/- 0.6 and 7.3 +/- 0.8 at 1, 4 or 8 weeks of CsA treatment, respectively. Vascular permeability was 10.3 +/- 1.2 for the control group and 15 +/- 1; 17.2 +/- 1.3, and 22.1 +/- 2.1 ug EB/g T; at 1, 4 or 8 weeks of CsA treatment, respectively Nitric oxide level was 3.5 +/- .9 umol/mg P for the control group and 4 +/- 0.2, 8.2 +/- 0.9 and 11 +/- 1 for 1, 2 or 8 weeks of CsA treatment, respectively. These findings appear to indicate that the development of significant gingival changes induced by CsA is related to new-onset of diabetes mellitus during the immunosuppressive treatment.
Subject(s)
Cyclosporine/adverse effects , Gingival Overgrowth/chemically induced , Hyperglycemia/chemically induced , Immunosuppressive Agents/adverse effects , Animals , Blood Glucose/analysis , Blood Glucose/drug effects , Capillary Permeability/drug effects , Collagen/analysis , Collagen/drug effects , Coloring Agents , Diabetes Mellitus/chemically induced , Evans Blue , Gingiva/drug effects , Gingiva/pathology , Male , Nitric Oxide/analysis , Random Allocation , Rats , Rats, Wistar , Time FactorsABSTRACT
La gingivopatía diabética ha sido reconocida no como una enfermedad infecciosa loca, sino como una enfermedad crónica inflamatoria para los tejidos gingivales. La diabetes parece contribuir a la mayor presencia de bacterias en la encía; sin embargo, es totalmente discutible que existen cambios cualitativos o cuantitativos entre la flora periodontopática diabética y no diabética. La enfermedad periodontal es una afección que tiene como respuesta un cuadro crónico inflamatorio. La disminución de insulina a consecuancia de alteraciones metabólicas induce hiperglucemia progresiva, lo que determina importantes factores de riesgo para las complicaciones orgánicas. Este trabajo muestra los efectos de dos factores críticos en la gingivopatía diabética: el efecto prolongado de hiperglucemia diabética y el estado inflamatorio y los componentes que determinan la destrucción del tejido gingival. El tratamiento experimental de acuerdo con los resultados obtejidos muestra que no sólo el control de la hiperglucemia por insulina es importante, sino también el ataque a los factores inflamatorios por drogas específicas.
Subject(s)
Rats , Animals , Diabetes Mellitus, Experimental/chemically induced , Gingival Diseases/etiology , Periodontal Diseases/etiology , Insulin/metabolism , Quinine , Kallikreins/physiology , Collagen/physiology , Rats, Wistar , Data Interpretation, StatisticalABSTRACT
La gingivopatía diabética ha sido reconocida no como una enfermedad infecciosa loca, sino como una enfermedad crónica inflamatoria para los tejidos gingivales. La diabetes parece contribuir a la mayor presencia de bacterias en la encía; sin embargo, es totalmente discutible que existen cambios cualitativos o cuantitativos entre la flora periodontopática diabética y no diabética. La enfermedad periodontal es una afección que tiene como respuesta un cuadro crónico inflamatorio. La disminución de insulina a consecuancia de alteraciones metabólicas induce hiperglucemia progresiva, lo que determina importantes factores de riesgo para las complicaciones orgánicas. Este trabajo muestra los efectos de dos factores críticos en la gingivopatía diabética: el efecto prolongado de hiperglucemia diabética y el estado inflamatorio y los componentes que determinan la destrucción del tejido gingival. El tratamiento experimental de acuerdo con los resultados obtejidos muestra que no sólo el control de la hiperglucemia por insulina es importante, sino también el ataque a los factores inflamatorios por drogas específicas.(AU)
Subject(s)
Rats , Animals , Diabetes Mellitus, Experimental/chemically induced , Periodontal Diseases/etiology , Gingival Diseases/etiology , Quinine , Insulin/metabolism , Collagen/physiology , Rats, Wistar , Data Interpretation, Statistical , Kallikreins/physiologyABSTRACT
Diabetic nephropathy is associated with increased urinary albumin and reduce kallikrein excretion. Increased activity of the renal kallikrein-kinin system has been suggested as one of the possible mechanisms underlying diabetic hyperfiltration. The present study shown that kallikrein-kinin system is progressively increased in the diabetic-pregnant rats at 7, 14, 21 days; 48 and 7 days after pregnancy (P<0.05 vs Control). However, this increase during diabetic pregnancy did not reached the levels of control pregnancy. On the other hand albumin excretion shown a significant and progressive renal damage in the diabetic state. These findings suggest that the diabetic pregnancy could impair the renal hemodynamic, but, on the other side could modulate the vasodilatador system at pregnancy in the attempt protect the fetus.
Subject(s)
Female , Humans , Animals , Pregnancy , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/pathology , Kallikreins/urine , Pregnancy in Diabetics/pathology , Blood Pressure , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/physiopathology , Pregnancy in Diabetics/physiopathology , Rats, WistarABSTRACT
Diabetic nephropathy is associated with increased urinary albumin and reduce kallikrein excretion. Increased activity of the renal kallikrein-kinin system has been suggested as one of the possible mechanisms underlying diabetic hyperfiltration. The present study shown that kallikrein-kinin system is progressively increased in the diabetic-pregnant rats at 7, 14, 21 days; 48 and 7 days after pregnancy (P<0.05 vs Control). However, this increase during diabetic pregnancy did not reached the levels of control pregnancy. On the other hand albumin excretion shown a significant and progressive renal damage in the diabetic state. These findings suggest that the diabetic pregnancy could impair the renal hemodynamic, but, on the other side could modulate the vasodilatador system at pregnancy in the attempt protect the fetus. (AU)
