Brain Oxidative Stress During Experimental Sepsis Is Attenuated by Simvastatin Administration

Author(s)

Rocha Catalao, Carlos Henrique ^[1] ; Santos-Junior, Nilton Nascimento ^[1] ; Angenendt da Costa, Luis Henrique ^[1] ; Souza, Anderson Oliveira ^[2] ; Alberici, Luciane Carla ^[2] ; Alves Rocha, Maria Jose ^[3]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Molecular Neurobiology; v. 54, n. 9, p. 7008-7018, NOV 2017.
• Web of Science Citations: 10

Abstract

During sepsis, brain damage is associated with oxidative stress due to overproduction of reactive oxygen species (ROS). Although there are recent reports about the benefits of statins in experimental sepsis and endotoxemia in peripheral organs, little is known about their effects in the CNS. Here, we investigated the antioxidant properties of simvastatin and its possible neuroprotective role during experimental sepsis. Male Wistar rats (250-300 g) were submitted to cecal ligation and puncture (CLP, n = 34) or remained as non-manipulated (naive, n = 34). Both groups were treated by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline. The animals submitted to CLP were treated 4 days before and 48 h after surgery. One animal group was decapitated and the blood and brain were collected to quantify plasma levels of cytokines and assess astrogliosis and apoptosis in the prefrontal cortex and hippocampus. Another group was perfused with PBS (0.01 M), and the same brain structures were dissected to analyze oxidative damage. The CLP rats treated with simvastatin showed a reduction in nitric oxide (P < 0.05), IL1-beta (P < 0.001), IL-6 (P < 0.01), and TBARS levels (P < 0.001) and an increase in catalase activity (P < 0.01), citrate synthase enzyme (P < 0.05), and normalized GSH/GSSG ratio. In addition, the histopathological analysis showed a reduction (P < 0.001) in reactive astrocytes and caspase 3-positive apoptotic cells. The results suggest a possible neuroprotective effect of simvastatin in structures responsible for spatial learning and memory and indicate the need for behavioral studies evaluating the impact on cognitive damage, as frequently seen in patients surviving sepsis. (AU)

• FAPESP's process: 10/17259-9 - Studies on mechanisms of mitochondrial uncoupling by non-esterified fatty acids as a strategy for prevention / treatment of obesity
• Grantee: Luciane Carla Alberici
• Support Opportunities: Research Grants - Young Investigators Grants