The renoprotective effects of Heme Oxygenase-1 during contrast-induced acute kidney injury in preclinical diabetic models

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus. METHODS: Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses. RESULTS: CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment. CONCLUSIONS: Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.

Altered liver morphology and enzymes in streptozotocin induced diabetic rats / Morfología y enzimas del hígado alteradas en ratas con diabetes inducida por estreptozotocina

This study was undertaken to evaluate the relationship and effects of diabetes on liver morphology, architecture and function. The hepatic effects of diabetes were evaluated in vivo using streptozotocin (STZ)-induced diabetic rats as an experimental model. The degree of hepatic dysfunction was measured by using biochemical parameters like serum transaminases (ALT and AST), alkaline phosphatase (ALP)and pseudocholinesterase (PChE) while the histopathological studies were carried out to support the enzymic Parameters. The aim of the study was to investigate the association between diabetic hepatic complications and liver enzyme alterations. This study was performed in the Department of Anatomy; Institute of Pharmaceutical Sciences and Institute of Diabetology and endocrinology of Baqai Medical University, Karachi. Diabetes was induced by a single dose of STZ (45 mg/kg, b.w.) given intraperitoneally in sodium citrate buffer at pH 4.5. Eighty albino rats were divided into five groups: control (A) and STZ treated (B, C, D, and E) which were sacrificed 2, 4, 6 and 8 weeks post treatment respectively. Histopathological examination of liver showed accumulation of lipid droplets, lymphocytic infiltration, increased fibrous content, dilatation and congestion of portal vessels and proliferation of bile ducts. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP and PChE were observed in the liver. It seems that the diabetic complications in the liver like hepatocyte destruction etc. are likely to be due to alterations in enzyme levels.

Este estudio se realizó para evaluar la relación y los efectos de la diabetes sobre la morfología, arquitectura y la función del hígado. Los efectos hepáticos de la diabetes se evaluaron in vivo utilizando estreptozotocina (STZ) para inducir diabetes en ratas como un modelo experimental. El grado de disfunción hepática se midió mediante el uso de parámetros bioquímicos, como las transaminasas séricas (ALT y AST), fosfatasa alcalina (ALP) y pseudocolinesterasa (PChE), mientras que los estudios histopatológicos se llevaron a cabo para apoyar los parámetros enzimáticos. El objetivo del estudio fue investigar la asociación entre las complicaciones hepáticas diabéticas y la alteración de enzimas hepáticas. Este estudio se realizó en el Departamento de Anatomía, Instituto de Ciencias Farmacéuticas y el Instituto de Diabetología y Endocrinología de la Baqai Medical University, Karachi. La diabetes fue inducida por una dosis única de STZ (45 mg/kg de peso corporal) administrada por vía intraperitoneal en tampón citrato de sodio a pH 4,5. Ochenta ratas albinas se dividieron en cinco grupos: control (A) y tratados con STZ (B, C, D y E), las que se sacrificaron a las 2, 4, 6 y 8 semanas después del tratamiento. El examen histopatológico de hígado mostró acumulación de gotitas de lípidos, infiltración linfocítica, aumento del contenido de fibras, dilatación y congestión de los vasos portales, y la proliferación de conductos biliares. Aumento de los niveles de aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), ALP y PChE fueron observados en el hígado. Parece que las complicaciones de la diabetes en el hígado como la destrucción de los hepatocitos etc., son probablemente debido a alteraciones en los niveles de las enzimas.

Analysis of myenteric neurons of the cecum of diabetic rats after supplementation with ascorbic acid / Análisis de neuronas mientéricas del ciego de ratas diabéticas después de suplementación con ácido ascórbico

The objective of this work was to investigate the neuroprotective action of the ascorbic acid over the myenteric neurons in the cecum of Wistar rats, four months after induction of the diabetes mellitus experimental with streptozotocin. Three groups with five rats each were used: C- controls, D- diabetic, DA- diabetic treated with ascorbic acid. For evidentiation of the myenteric neurons was carried out to Giemsa's technique. Were evaluated the areas of cell bodies of 500 neurons in each group studied. The quantitative analysis was carried out in an area of 16.6 mm2 in each cecum studied. In the animals diabetic observed elevation of the glycemia and glycated hemoglobin. The supplementation with ascorbic acid was effective under the myenteric neurons of the cecum of diabetics rays, since was presented the effect neuroprotective and neurotrofic.

El objetivo de este trabajo fue verificar el efecto neuroprotector del ácido ascórbico sobre las neuronas mientéricas en el ciego de Rattus Wistar, cuatro meses después de la inducción de diabetes mellitus experimental con estreptozotocina. Utilizamos tres grupos de animales: C- control, D- diabético, DA- diabético tratado con ácido ascórbico. Para la observación de las neuronas mientéricas fue llevado a cabo la técnica de Giemsa. Fueron evaluadas las áreas del soma de 500 neuronas, en cada grupo estudiado. El análisis cuantitativo fue llevado a cabo, en cada ciego, en un área de 16,6 mm². En los animales diabéticos, se observó la elevación de la glicemia y de la hemoglobina glicosilada. La suplementación con ácido ascórbico fue efectiva en las neuronas mientéricas del ciego de animales diabéticos, ya que se produjeron los efectos neuroprotetor y neurotrófico.