Background And Aim: Tetrahydrobiopterin (BH) is an essential co-factor that regulates nitric oxide (NO) and reactive oxygen species (ROS) production by nitric oxide synthases (NOS). In this study, we evaluated the effects of sepsis on BH level and redox status in the brain by using the rat model of sepsis-induced by cecal ligation and puncture (CLP) and examined whether BH and/or acetyl-L-carnitine (ALC) could prevent the neuronal apoptosis and neurological changes induced by sepsis.
Material And Method: Male albino rats were randomly and blindly divided into 8 groups: sham, sham + BH, sham + ALC, sham +BH+ ALC, CLP, CLP + BH, CLP + ALC, and CLP+BH+ ALC. We measured neurological indicators, brain levels of BH, guanosine triphosphate cyclohydrolase (GTPCH), sepiapterin reductase (SR) and dihydropteridine reductase (DHPR) genes expression (Essential enzymes in BH biosynthesis and recycling pathways). We investigated also brain redox status and both endothelial and inducible NOS expressions.
Results: Brain of septic rats demonstrated a reduced BH bioavailability, downregulation of BH synthetic enzymes, increased production of hydrogen peroxide and impaired antioxidant enzymes activities. Treatments with BH and/or ALC increased BH level, upregulated BH synthetic enzymes expressions, and attenuated oxidative-induced neuronal apoptosis.
Conclusion: Our results suggest that BH and/or ALC might protect the brain against oxidative stress induced neuronal apoptosis by restoring bioavailability of BH and upregulating of BH synthetic enzymes in the brain during sepsis.
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