The effect of gingival aging in diabetic and non-diabetic status: an experimental study.

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.

The effect of gingival aging in diabetic and non-diabetic status: an experimental study / El efecto del envejecimiento gingival en el estado diabetico y no diabetico. Estudio experimental

Major gingivalperiodontal changes according to age have been observed in both diabetic and nondiabetic rats. Male Wistar rats weighing 200220 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, nondiabetic gingival modifications develop naturally with age, while in aging associated to diabetic disease, hyperglycemia increases progressively and early (AU)

Se han observados importantes cambios gingivoperiodontales en función de la edad tanto en ratas no diabéticas como en ratas diabéticas. Ratas machos Wistar de 200220 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 /kg). 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 E gingival. En tanto que en el estado diabético los cambios del estrés oxidativo, PV y E gingival se observan temprano y fueron progresivamente más significa tivos 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 (AU)

Oxidative stress in the optic nerve and cortical visual area of steptozotocin-induced diabetic Wistar rats: Blockade with a selective bradykinin B1 receptor antagonist.

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.

Relación entre el estrés oxidativo diabético y la enfermedad periodontal. Estudio experimental / Relation between diabetes oxidative stress and periodontal disease

Introducción: la diabetes mellitus comprende un grupo de desórdenes caracterizados por la alterada tolerancia a la glucosa y el deterioro del metabolismo de lípidos y carbohidratos. La enfermedad diabética se asocia con numerosas complicaciones directamente resultantes de la hiperglucemia. Dentro de las complicaciones, una de las más importantes es la enfermedadperiodontal (EP) por los procesos de estrés oxidativo causados por la patología diabética. El objetivo de este trabajo es describir el efecto de la patología diabética sobre los factores antioxidantes y oxidantes que afectan a la enfermedad periodontal. Materiales y métodos: ratas Wistar machos fueron inyectadas con streptozotocin (STZ, 65mg/kg). Se obtuvieron muestras deencía y sangre para determinaciones bioquímicas. Al final de la cuarta semana, en las muestras se determinaron las glucemias, peroxidación lipídica medida por el malondialdehído (MDA), glutatión reducido (GSH) y óxido nítrico (ON).Resultados: la diabetes produjo cambios significativos en las glucemias como así también en el estrés oxidativo en encía y plasma, con aumento de la peroxidación lipídica (MDA) y ON. En cuanto a la actividad antioxidante de GSH, se observó una significativa reducción en encía y plasma comparada con los controles. Conclusión: la diabetes afecta todos los parámetros oxidantes y antioxidantes del plasma y la encía, disminuyendo la capacidad de defensas y causando daños en los tejidos periodontales.

Relación entre el estrés oxidativo diabético y la enfermedad periodontal. Estudio experimental / Relation between diabetes oxidative stress and periodontal disease

Introducción: la diabetes mellitus comprende un grupo de desórdenes caracterizados por la alterada tolerancia a la glucosa y el deterioro del metabolismo de lípidos y carbohidratos. La enfermedad diabética se asocia con numerosas complicaciones directamente resultantes de la hiperglucemia. Dentro de las complicaciones, una de las más importantes es la enfermedadperiodontal (EP) por los procesos de estrés oxidativo causados por la patología diabética. El objetivo de este trabajo es describir el efecto de la patología diabética sobre los factores antioxidantes y oxidantes que afectan a la enfermedad periodontal. Materiales y métodos: ratas Wistar machos fueron inyectadas con streptozotocin (STZ, 65mg/kg). Se obtuvieron muestras deencía y sangre para determinaciones bioquímicas. Al final de la cuarta semana, en las muestras se determinaron las glucemias, peroxidación lipídica medida por el malondialdehído (MDA), glutatión reducido (GSH) y óxido nítrico (ON).Resultados: la diabetes produjo cambios significativos en las glucemias como así también en el estrés oxidativo en encía y plasma, con aumento de la peroxidación lipídica (MDA) y ON. En cuanto a la actividad antioxidante de GSH, se observó una significativa reducción en encía y plasma comparada con los controles. Conclusión: la diabetes afecta todos los parámetros oxidantes y antioxidantes del plasma y la encía, disminuyendo la capacidad de defensas y causando daños en los tejidos periodontales.(AU)

Bradykinin B1 antagonism inhibits oxidative stress and restores Na+K+ ATPase activity in diabetic rat peripheral nervous system.

Diabetic peripheral neuropathy is one the most common complications of diabetes mellitus and frequently results in clinically significant morbidities such as pain, foot ulcers and amputations. The diabetic condition progresses from early functional changes to late, poorly reversible structural changes. The chronic hyperglycemia measured alongside diabetes development is associated with significant damage and failure of various organs. In the present study diabetes was induced in male Wistar rats by a single dose of streptozotocin (STZ) and the association between the BKB1-R and the oxidative stress and Na+-K+ ATPase activity in nervous tissues was analysed. The results showed that the resulting hyperglycemia induced a reduction of the neuronal electrical function integrity and increased oxidative stress in the sciatic nerve homogenates of 30 days diabetic rats. Malondialdehyde (MDA) used as a marker of oxidative stress was elevated whereas Biological Antioxidant Potential (BAP), glutathion (GSH) levels and superoxide dismutase (SOD) activity were decreased. Treatment of the rats 3 days before the end of the 4 week period with the BKB1 antagonist R-954 restored the neuronal activity and significantly attenuated the oxidative stress as shown by the level of the various markers returning close to levels found in control rats. Our results suggest that the BKB1-R subtype is overexpressed in sciatic nerve during the STZ-induced diabetes development as evidenced by inhibitory effects of the BKB1-R antagonist R-954. The beneficial role of BKB1-R antagonist R-954 for the treatment of diabetic neuropathy is also suggested.

Blockade of early and late retinal biochemical alterations associated with diabetes development by the selective bradykinin B1 receptor antagonist R-954.

The chronic hyperglycemia measured alongside diabetes development is associated with significant long-term damage and failure of various organs. In the present study it was shown that hyperglycemia induced early and long term increases in nitric oxide (NO) levels, kallikrein activity and vascular capillary permeability measured as plasma extravasation, and decreases of Na/K ATPase activity in diabetic rat retina 4 and 12 weeks after streptozotocin (STZ) injection. Treatment of the animals for 5 consecutive days with a novel selective bradykinin B(1) receptor (BKB(1)-R) antagonist R-954 (2mg/kg s.c) at the end of the 4 and 12 week periods highly reduced NO, kallikrein and capillary permeability and increased Na/K ATPase activity in the retina. These results suggest that the BKB(1)-R receptor subtype is over-expressed during the streptozotocin-induced development of diabetes in rat retina as evidenced by the inhibitory effects of the BKB(1)-R antagonist R-954 on NO, kallikrein and vascular permeability increases as well as Na/K ATPase decreases. The beneficial role of the BKB(1)-R antagonist R-954 for the treatment of the diabetic retinopathy is also suggested.

Side effects of cyclosporine-A treatment in rats: gingival overgrowth and early hyperglycemia

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.

Antidiabetic efficacy of bradykinin antagonist R-954 on glucose tolerance test in diabetic type 1 mice.

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).

Side effects of cyclosporine-A treatment in rats: gingival overgrowth and early hyperglycemia.

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 diabetes mellitus experimental y las alteraciones de los tejidos blandos en periodoncia: efectos de la insulina y de un antagonista del receptor de cininas / Experimental diabetes mellitus and soft tissue alterations in periodontics: effects of insulin and a kinin receptor antagonist

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.

La diabetes mellitus experimental y las alteraciones de los tejidos blandos en periodoncia: efectos de la insulina y de un antagonista del receptor de cininas / Experimental diabetes mellitus and soft tissue alterations in periodontics: effects of insulin and a kinin receptor antagonist

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)

Diabetes and its effects on dental pulp.

Uncontrolled or poorly controlled diabetes mellitus may be a risk factor for the development of oral complications. The objective of this investigation was to determine the effect of diabetes mellitus progression on inflammatory and structural components of dental pulp. Male Wistar rats were given a single injection of Streptozotocin (STZ), and induction of diabetes was confirmed 24 h later. Dental pulp tissue samples were taken from central incisors and molars of diabetic rats 30 and 90 days after the STZ treatment. Plasma glucose levels in diabetic rats 30 and 90 days after STZ treatment were significantly increased when compared to control rats (P < 0.001). Nitrite and kallikrein levels in dental pulp tissue were higher in diabetic rats 30 days after STZ treatment than in controls, while only nitrite were decreased 90 after of STZ treatment. Myeloperoxidase activity showed changes 30 and 90 days after STZ injection when compared to controls. The activity of alkaline phosphatase showed significant changes 30 and 90 days after STZ treatment. On the other hand the concentration of collagen was decreased in diabetic rats 30 and 90 days after STZ injection. These results suggest that diabetes is a critical factor that has profound effects upon oral tissues, resulting in expression of inflammatory mediators and modifications of structural components of dental pulp.

The development of insulitis and the kallikrein-kinin system.

Data derived from animals and humans suggest that the onset of diabetes is associated with hemodynamic changes in the renal circulation leading to increased renal plasma flow (RPF), glomerular capillary hyperfusion, and an increased glomerular transcapillary hydraulic pressure gradient. The duration of diabetes is one of the most important factors in predicting the development of diabetic nephropathy. On the other hand, diabetic nephropathy has been associated with the degree of hyperglycemia; thus, hyperglycemia may therefore contribute to alterations in structure and function of the kidney. In the present paper, we investigated early alterations of renal function in C57BL/KSJ mdb male mice that were injected with sub-diabetogenic doses of STZ. Urinary protein excretion (UPE) increased significantly at 12 and 18-20 days after STZ with a glucose level of 4-6 mm/l; the progressive increase of glycemia was followed by a progressive increase of UPE. In a similar way, urinary nitrite (NO2-) was also significantly increased. Urinary kallikrein excretion started to increase at a level of 4-6 mmol/l blood glucose concentration (BGC) 8 days after administration of STZ, and kidney vascular permeability also increased following the increment of BGC. These results confirm the presence of early modifications of renal function prior to the clinical detection of diabetic hyperglycemia.

Renal function in the diabetic pregnant rats

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.

Renal function in the diabetic pregnant rats

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)

Effects of L-NAME and L-Arg on arterial blood pressure in normotensive and hypertensive streptozotocin diabetic rats

The present study was designed to examine blood pressure response to nitric oxide synthase-pathway inhibition and stimulation in normotensive and hypertensive diabetic rats. Rats treated with streptozotocin (60 mg/Kg ip) developed high blood glucose, polyuria and slow weight gain compared with control. One group of diabetic rats developed hypertension, consequently we studied three experimental groups: control rats (C), normotensive diabetic rats (ND) and hypertensive diabetic rats (HD). Mean arterial pressure (MAP), systolic blood pressure, diastolic blood pressure and heart rate were recorded: baseline time, 30'after L-nitro arginine methyl ester (L-NAME: 1 mg/Kg iv) and post L-arginine (L-arg: 250 mg/Kg iv) injection. L-NAME induced a significantly increase in MAP in all groups. This enhancement was smaller in diabetic than in control rats. The increase in MAP in HD was significantly lower than that in NDL-arg induced a significantly decrease in MAP in all groups. This decrease was significantly attenuated in diabetic compared with control rats. The degree of hypotension in response to L-arg in diabetic groups was lower in hypertensive than that in normotensive diabetic rats. These data suggest that an impairment of nitric oxide formation could be involved in the development of hypertension in this model.

Effects of L-NAME and L-Arg on arterial blood pressure in normotensive and hypertensive streptozotocin diabetic rats

The present study was designed to examine blood pressure response to nitric oxide synthase-pathway inhibition and stimulation in normotensive and hypertensive diabetic rats. Rats treated with streptozotocin (60 mg/Kg ip) developed high blood glucose, polyuria and slow weight gain compared with control. One group of diabetic rats developed hypertension, consequently we studied three experimental groups: control rats (C), normotensive diabetic rats (ND) and hypertensive diabetic rats (HD). Mean arterial pressure (MAP), systolic blood pressure, diastolic blood pressure and heart rate were recorded: baseline time, 30after L-nitro arginine methyl ester (L-NAME: 1 mg/Kg iv) and post L-arginine (L-arg: 250 mg/Kg iv) injection. L-NAME induced a significantly increase in MAP in all groups. This enhancement was smaller in diabetic than in control rats. The increase in MAP in HD was significantly lower than that in NDL-arg induced a significantly decrease in MAP in all groups. This decrease was significantly attenuated in diabetic compared with control rats. The degree of hypotension in response to L-arg in diabetic groups was lower in hypertensive than that in normotensive diabetic rats. These data suggest that an impairment of nitric oxide formation could be involved in the development of hypertension in this model. (AU)