Systemic inflammation biomarkers in 6-OHDA- and LPS-induced Parkinson’s disease in rats

Abstract

Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)-and lipopolysaccharide (LPS)-induced models of Parkinson's disease (PD). Experiments were carried out on adult male Wistar rats: 1 -intact animals; 2 -sham-operated animals and 3 -6-OHDAand LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and shamoperated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology.

The Protection of EGCG Against 6-OHDA-Induced Oxidative Damage by Regulating PPARγ and Nrf2/HO-1 Signaling

“… 33 One of the proposed mechanisms of 6-OHDA toxicity is its ability to induce inflammation. 34 , 35 Inflammatory factors, such as TNFα could directly activate cell apoptotic pathway or indirectly suppress the mitochondrial function. Considerable evidence from in vitro and in vivo studies suggests that inflammation is related to ROS generation in PD, 36 , 37 and increased ROS level could augment the inflammation process, 38 , 39 thereby exacerbating neuronal damage.…”

Rosemary: Unrevealing an old aromatic crop as a new source of promising functional food additive—A review

“…Various inflammatory stimuli such as LPS are able to initiate different chronic inflammatory diseases (Oliynyk et al., 2023). Rosemary extracts, which were rich in carnosic acid derivatives, can significantly reduce the capability of LPS‐stimulated RAW 264.7 cells to produce NO (Brindisi et al., 2020).…”