Protective effect of Rosuvastatin on Azithromycin induced cardiotoxicity in a rat model.

AIMS: Azithromycin is widely used broad spectrum antibiotic recently used in treatment protocol of COVID-19 for its antiviral and immunomodulatory effects combined with Hydroxychloroquine or alone. Rat models showed that Azithromycin produces oxidative stress, inflammation, and apoptosis of myocardial tissue. Rosuvastatin, a synthetic statin, can attenuate myocardial ischemia with antioxidant and antiapoptotic effects. This study aims to evaluate the probable protective effect of Rosuvastatin against Azithromycin induced cardiotoxicity. MAIN METHOD: Twenty adult male albino rats were divided randomly into four groups, five rats each control, Azithromycin, Rosuvastatin, and Azithromycin +Rosuvastatin groups. Azithromycin 30 mg/kg/day and Rosuvastatin 2 mg/kg/day were administrated for two weeks by an intragastric tube. Twenty-four hours after the last dose, rats were anesthetized and the following measures were carried out; Electrocardiogram, Blood samples for Biochemical analysis of lactate dehydrogenase (LDH), and creatine phosphokinase (CPK). The animals sacrificed, hearts excised, apical part processed for H&E, immunohistochemical staining, and examined by light microscope. The remaining parts of the heart were collected for assessment of Malondialdehyde (MDA) and Reduced Glutathione (GSH). KEY FINDINGS: The results revealed that Rosuvastatin significantly ameliorates ECG changes, biochemical, and Oxidative stress markers alterations of Azithromycin. Histological evaluation from Azithromycin group showed marked areas of degeneration, myofibers disorganization, inflammatory infiltrate, and hemorrhage. Immunohistochemical evaluation showed significant increase in both Caspase 3 and Tumor necrosis factor (TNF) immune stain. Rosuvastatin treated group showed restoration of the cardiac muscle fibers in H&E and Immunohistochemical results. SIGNIFICANCE: We concluded that Rosuvastatin significantly ameliorates the toxic changes of Azithromycin on the heart.

Effects of insulin and metformin on fetal kidney development of streptozotocin-induced gestational diabetic albino rats.

Gestational diabetes mellitus is one of common medical complications of pregnancy. Hyperglycemia in utero impairs renal development and produces renal anomalies. Metformin has antioxidant properties and better glycemic control. Aim: assessment insulin and metformin effects on renal development of streptozotocin-induced gestational diabetic albino rats. Sixty virgin female albino rats were used. Once pregnancy confirmed, animals were randomly assigned into control, metformin, diabetic, diabetic plus insulin, diabetic plus metformin and diabetic plus insulin and metformin treated groups. Rats were sacrificed on the 20th day of gestation; fetuses were extracted and weighted. Fetal kidneys were extracted prepared for light, morphometric and electron microscopic examination. Diabetic followed by diabetic plus metformin treated groups revealed retardation of glomerular development in the cortical and Juxtaglomerular zones with a significant increase in the early immature glomerular stages and immature to mature glomerular ratio compared to other groups. Diabetic group also showed morphometric changes, shrunken and empty glomeruli, vacuolar degeneration and hemorrhage. Diabetic plus metformin group showed minimal improvement while diabetic plus insulin and diabetic plus insulin and metformin groups showed developmental, histopathological and morphometric improvement with best results in the combination group. Gestational diabetes mellitus (GDM) possess deleterious effects on fetal kidney development. Insulin improves the glycemic state and decreases GDM effects on fetal kidneys. Metformin produces mild protection while the combination of insulin and metformin produces the best glycemic control and protect fetal kidneys.