Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Effect of Calcitriol on the Renal Microvasculature Differentiation Disturbances Induced by AT1 Blockade During Nephrogenesis in Rats.

Alterations in the renal vasculature during fetal programming can cause disturbances in renal structure and function that persist into adulthood. Calcitriol can affect cellular differentiation and proliferation, and promote endothelial cell maintenance, each of which is a key event in nephrogenesis. Calcitriol is a negative endocrine regulator of the renin gene. Rats exposed to renin-angiotensin system (RAS) antagonists during lactation have been shown to develop renal disorders, which demonstrated that the RAS may play an important role in mammalian kidney development. We evaluated the effects of calcitriol administration on losartan [angiotensin II receptor antagonist (ANGII), AT1]-induced changes in renal differentiation in rats during lactation. Rats treated with losartan showed alterations in renal function and structure that persisted into adulthood. These disruptions included hydronephrosis, papillary atrophy, endothelial dysfunction, and aberrant endothelial structure. These changes were mitigated by treatment with calcitriol. The results of our study showed that animals exposed to AT1 blockade during lactation exhibited altered renal microvasculature differentiation in adulthood that was attenuated by treatment with calcitriol.

The Treatment of Prednisone in Mild Diabetic Rats: Biochemical Parameters and Cell Response.

BACKGROUND: Limited studies have been carried out with prednisone (PRED) in treatment by glucose intolerant individuals, even in this model the animals presented low blood glucose levels at adulthood, by the high regenerative capacity of ß-cell. OBJECTIVE: The aim was to evaluate the effects of the treatment of PRED in mild diabetes on biochemical and immunological biomarkers. METHODS: Rats were randomly divided into four groups: control (C), treated control C+PRED (treatment of 1.25 mg/Kg/day PRED); diabetic DM (mild diabetes) and treated diabetic DM+PRED (treatment with same dose as C+PRED group). Untreated groups received vehicle, adjusted volume to body weight. The treatment lasted 21 days and measured body weight, food and water intake, and glycemia weekly. In the 3rd week, the Oral Glucose Tolerance Test (OGTT) and the Insulin Tolerance Test (ITT) was performed. On the last day, the rats were killed and the blood was collected for biochemical analyzes, leukogram and immunoglobulin G levels. RESULTS: There was a significant decrease in body weight in mild diabetes; however, the treatment in diabetic groups increased food intake, glycemia, and the number of total leukocytes, lymphocytes and neutrophils. On the other hand, it decreased the levels of triglycerides, high-density and very lowdensity lipoproteins. In addition, diabetic groups showed glucose intolerance and mild insulin resistance, confirming that this model induces glucose intolerant in adult life. CONCLUSION: The results showed that the use of prednisone is not recommended for glucose intolerant individuals and should be replaced in order to not to aggravate this condition.