Study of the colistin nephrotoxicity

Abstract

Colistin is a mixture of two polymyxins (PMXs) PMX PMX E1 and E2. It is an antimicrobial drug used to treat infections caused by gram-negative bacteria; and can be obtained from the fermentation of the natural producer, Paenibacillus polymyxa var colistinus. The use of colistin has been avoided in the past because of its nephrotoxic effect, but since multiresistant bacterial infections started to appear, its use has been reconsidered. However, this drug may cause various toxic effects ranging from neurotoxicity, nephrotoxicity and other side effects that may involve various areas of the body. It is known that the drug may cause polyuria, glomerular filtration drop and hypomagnesemia. We propose to study the renal disorders related to the use of colistin: glomerular filtration (through creatinine clearance); pathways that may be involved by decrease of glomerular filtration (oxidative stress, nitric oxide, endothelin, cell cycle and Klotho), tubular function (by measuring diuresis, fractional excretion of ions and protein expression of the major sodium transporters and water the nephron). After the acclimation period, rats will receive 10 colistin dose of 3,000,000 IU / kg body weight / day diluted in 0.5 ml of distilled water, intraperitoneally for 7 days (Group Colistin) and 10 mice receive intraperitoneal saline for the same period (control group). In the third, fifth and seventh days, the animals will be placed in metabolic cage individually for 24h to 24h urine collection, and the experiment will be stopped on the eighth day, when the animals will be euthanized to collect blood and kidneys. Renal biochemical measurments (plasma and urine), western blotting analysus, and study of renal histology (for review score of injury) and immunohistochemistry will be performed.