Quinacrine, a PLA2 inhibitor, alleviates LPS-induced acute kidney injury in rats: Involvement of TLR4/NF-κB/TNF α-mediated signaling.

Acute Kidney Injury (AKI) is a major factor in sepsis-related mortality and may occur due to lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria that triggers a systemic acute inflammatory response. Quinacrine's (QC) renoprotective properties in sepsis and the underlying mechanism, however, are still not fully understood. This study was done to investigate the anti-inflammatory, antioxidative, and anti-apoptotic effects of QC, a phospholipase A2 (PLA2) inhibitor, against LPS-induced AKI. Rats were randomly divided into five groups: control group, QC30 group, LPS group, LPS+QC 10 group, and LPS+QC 30 group. The rats were administered intraperitoneally QC (10 and 30 mg/kg) for 3 days (once a day) prior to injection of LPS (3 mg/kg). Six hours after the LPS injection, the histopathological changes, oxidative stress, inflammation, and apoptosis in the collected kidney tissues were detected by hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and immunohistochemistry staining, respectively. QC pretreatment could successfully attenuate LPS-induced AKI, as evidenced by a decrease in tissue histopathological injury. Meanwhile, QC alleviated LPS-induced kidney oxidative stress; it reduced MDA levels and increased levels of SOD, CAT, GPX, and GSH. LPS-induced elevations in kidney TLR4, NF-κB, TNF-α, IL-1ß, IL-6, PLA2, caspase 3, and Bax contents were significantly attenuated in QC-treated groups. Our findings revealed a significant effect of QC: protecting against LPS-induced AKI through inhibition of PLA2 and decreasing inflammation, oxidative stress, and apoptosis. To treat LPS-induced AKI, QC may be an effective substance with an excellent protection profile.

Insulin-like growth factor-1 expression levels in pro-inflammatory response in calves with neonatal systemic inflammatory response syndrome.

The objective of this study was to investigate the mRNA expression of insulin-like growth factor-1 (IGF-1), pro-inflammatory cytokines (IL-1ß, IL-6, IL-18, and TNF-α), serum immunoglobulin profiles (IgG and IgM), and lipid peroxidation status (MDA) in relation to pro-inflammatory cytokines. A case-controlled, prospective, and observational investigation was completed on 85 calves. Total RNA was isolated from whole blood samples of both the SIRS and healthy calves, followed by reverse transcription into cDNA. The resulting cDNAs were mixed with iTaq Universal SYBR Green Supermix and primers specific to the relevant genes using the Rotor-Gene Q instrument. After the reaction was completed, gene expressions were normalised against ß-actin using the 2-ΔΔCT method. The mRNA levels of pro-inflammatory cytokines namely (IL-1ß [SIRS: 2.15 ± 0.55, Control: 1.13 ± 0.62; P = 0.001], IL-6 [SIRS: 2.82 ± 0.52, Control: 0.91 ± 0.11; P < 0.001], IL-18 [SIRS: 1.92 ± 0.41, Control: 0.99 ± 0.13; P < 0.001], and TNF-α [SIRS: 2.59 ± 0.28, Control: 0.93 ± 0.09; P < 0.001]) and IGF-1 (SIRS: 3.55 ± 0.55, Control: 0.91 ± 0.15; P < 0.001) were up-regulated in calves with SIRS, while serum IgG (SIRS: 4.16 ± 0.26, Control: 1.73 ± 0.17; P < 0.001), IgM (SIRS: 1.55 ± 0.11, Control: 1.09 ± 0.13; P < 0.001), and MDA levels (SIRS: 41.12 ± 3.48, Control: 3.76 ± 0.81; P < 0.001) increased significantly in these calves. Furthermore, significant (P < 0.01) positive correlations were found in calves with SIRS in relation to the expression levels of IL-1ß, IL-6, IL-18, TNF-α, IGF-1, serum immunoglobulins, and MDA levels. These results suggest that IGF-1 could be a valuable pro-inflammatory marker, considering its high positive correlation with the expression levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-18, and TNF-α) and markers (MDA, IgG, and IgM) in calves with SIRS.

Evaluation of erythrocyte arginase activity, plasma nitric oxide concentration and oxidative stress status in cattle with anaplasmosis.

Bovine anaplasmosis is an arthropod-borne disease characterized by high fever, anaemia and sometimes jaundice. The role of oxidative stress in anaplasmosis has been investigated, but erythrocyte arginase (ARG) activity has not been studied. In this study, we aimed to investigate the changes in haematological parameters, erythrocyte ARG activity, plasma nitric oxide (NO) levels and oxidative stress parameters and explain the relationship between each other in cattle with anaplasmosis. The material of this study consisted of 14 cattle, aged 10-12 months with anaplasmosis (infected group) and 14 healthy cattle aged 10-12 months (control group). Our data revealed that leukocyte parameters and plasma NO levels and serum malondialdehyde (MDA), total oxidant status (TOS) and oxidative stress index (OSI) levels were higher while erythrocyte parameters, erythrocyte ARG activity and serum total antioxidant status (TAS) and glutathione (GSH) levels were lower in the infected group compared to the control group. There was a strong correlation between erythrocyte ARG activity and NO, MDA, TOS, OSI, TAS and GSH. ROC analysis and correlation results suggest that erythrocyte ARG activity is an effective oxidative stress marker. We concluded that severe oxidative stress occurs in anaplasmosis. As the severity of anaemia increases, erythrocyte ARG activity plummets while plasma NO level elevates. These two parameters may also be used as prognostic and oxidative stress markers. Although decreased erythrocyte ARG activity is a disadvantage in haemolytic diseases, this situation can be compensated by increased NO. Thus, homeostasis of these two parameters may contribute to the elimination of the infection.

Canine distemper virus induces downregulation of GABAA,GABAB, and GAT1 expression in brain tissue of dogs.

The aim of the study was to determine the expression profiles of GABAA, GABAB, and GAT1 using RT-PCR and the immunoreactivity of GAT1 via immunohistochemical and immunofluorescence assays in CDV-infected brain tissue of dogs. For this purpose, dogs with CDV and dogs without CDV were selected. The mRNA transcript levels of GABAA, GABAB, and GAT1 were significantly downregulated in brain tissue in the CDV-infected group as compared with that in non-CDV-infected brain tissue in the control group (p < 0.01, p < 0.001). In addition, the immunoreactivity of GAT1 in CDV-infected brain tissue was significantly lower than in the uninfected group (p < 0.05). We conclude that one of the main causes of myoclonus in CDV infections may be the blockage of postsynaptic inhibition in neurons or a lack of metabolism of GABA. In addition, a GABA neurotransmission imbalance could play a role in demyelination in CDV infections.