The effects of hydroxyurea on proinflammatory cytokine and tissue histopathology in an experimental sepsis model.

Abstract

The diagnosis and treatment of sepsis are costly to healthcare services, and it is an important disease with high mortality rates. In the pathogenesis of sepsis, for which we still cannot provide a complete cure, there is increased cytokine release and organ damage. Hydroxyurea has been shown to reduce leukocyte counts, decrease inflammatory cytokines, and limit organ inflammation in ischemia-reperfusion models. This study aimed to evaluate leukocyte counts, interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) cytokine values and organ inflammatory processes in hydroxyurea-treated rats with an experimental sepsis model. After ethical approval, rats were randomly divided into three groups, control (n= 7), sepsis (n= 7), and hydroxyurea (n= 7). Sepsis was created using the cecal ligation and puncture (CLP) method in rats other than in the control group. Rats in the hydroxyurea group received hydroxyurea (200 mg/kg) intragastrically, and the control and sepsis groups received sterile distilled water. IL-1β, IL-6, and TNF-α levels were measured at 0, 8, and 24 hours after CLP in all rats. Blood samples were collected at the time of sacrification 24 hours after CLP and analyzed for the complete blood count. Tissue specimens were taken for histopathologic examination. Cytokine levels (IL-1β, IL-6, TNF-α), white blood cell counts, and tissue damage were increased after the sepsis model in rats. It was found that the cytokine levels at the 8th hour, white blood cell count, and brain tissue damage in the hydroxyurea group were decreased significantly compared with the sepsis group. Early hydroxyurea treatment in rats with sepsis decreases proinflammatory cytokine (IL-1β, IL-6, and TNF-α) levels and thus reduces brain damage.