Investigating lipopolysaccharide-induced inflammation in Sprague-Dawley rats on liver function with specific focus on coagulation factor production

Abstract

Neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), have long confounded the scientific and medical communities. The extensive research into these diseases, particularly AD has produced several plausible theories on its progression, but this research has so far failed to yield any lasting results in producing an effective treatment of AD. With the increase of the prevalence of AD in an increasingly aging world population, elucidating a model of disease progression that takes into account the neurodegenerative characteristics that are hallmarks of the disease, along with its related metabolic and organ system effects has become a public health priority. Systemic inflammation has become one of the main components of several non-communicable diseases, in particular AD. In this study, the aim was to investigate an emerging theory of AD pathogenesis that may combine the neurological and metabolic aspects that are often seen in these patients, the gut-liver axis theory. This theory states that the liver is the first organ to come into contact with circulating lipopolysaccharide (LPS), which would cause the kind of low-grade and chronic inflammation that would cause significant long-term damage to the liver, thus resulting in the organ system failure secondary to AD. Therefore, a model of LPS-induced inflammation was studied in adult male Sprague-Dawley rats to determine the effect of the systemically -induced LPS inflammation on the liver with particular focus on coagulation factor production and the possible prevalence of liver damage and fibrosis. The model was successfully created over a 10-day period, after which the animals were terminated, and the liver tissuetissues collected and processed for use in light-microscopy and transmission electron microscopy (TEM). The levels of coagulation factors, tissue factor (TF) and fibrinogen (FG), were also determined by use of ELISA assays. Behavioural testing was used as a means to confirm the presence of AD-like symptoms in the model induced by the LPS administration. Due to the low concentration of LPS administered into the animals during the experimental period, the levels of tissue factor and fibrinogen were not significantly higher or changed when compared with the control group. Similarly, the morphological analysis of liver tissue showed that the administration of LPS as designed in this study did not significantly affect the liver tissue. At an organelle level, it was found that the LPS administration produced a mild to moderate negative effect on the liver, an indication of the initial stages of liver damage due to the exposure of LPS. In conclusion, the administration of LPS in Sprague-Dawley rats as modelled in this study did not induce the systemic inflammation that would cause significant liver damage and subsequent fibrosis, only producing the initial stages liver damage seen at sub-microscopic level. This however shows that short-term exposure to low levels of LPS will induce changes on a cellular level and that long-term exposure could accumulate to complications that could lead to clinical presentation. Key words: inflammation, lipopolysaccharide, liver