ABSTRACT
This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and anti-inflammatory cytokine and protecting against lung and liver injuries. Male Swiss albino mice were exposed to 0.2 Gy gamma radiation/week for four consecutive weeks then injected intraperitoneally (i.p) with a single dose of 8.3 × 106 CFU Escherichia coli/g b.w. then injected i.p. with 1.0 mg/kg cholecalciferol (Vit D3) for 7 days starting 4 h after E. coli injection. The results revealed that Cholecalciferol and low dose gamma radiation caused significant depletion in the severity of E. coli infection (colony forming unit per milliliter), log10 of E. coli, Tumor necrosis factor alpha, Interleukin 6, VEGF, alanine aminotransferase, and aspartate aminotransferase levels and significant elevation in IL-10, IL-4, and HO-1. Immunohistochemical analysis of caspase-3 expression in lung tissue section showed low caspase-3 expression in cholecalciferol and low dose gamma radiation treated group. Histopathological examinations were performed in both lung and liver tissues which also emphasis the biochemical findings. Our results exhibit the importance of cholecalciferol and low dose gamma radiation in improving liver function and providing anti-inflammatory response in diseases causing cytokine storm.
Subject(s)
Cholecalciferol , Escherichia coli Infections , Escherichia coli , Gamma Rays , Animals , Mice , Cholecalciferol/pharmacology , Male , Escherichia coli Infections/drug therapy , Escherichia coli Infections/pathology , Liver/pathology , Liver/drug effects , Liver/metabolism , Lung/pathology , Lung/metabolism , Cytokines/metabolism , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Aspartate Aminotransferases/bloodABSTRACT
BACKGROUND: Caspase-3 and granzyme B were claimed as apoptotic manipulative enzymes. AIMS: The present study was to determine the enzymes expression and activity in cancer and cancer immune therapeutic status and the possible association to cancer common pathological signs targeting the improvement of therapeutic conditions. MATERIAL AND METHODS: Mice were immunized with cell lyaste or cell lysate + CKI in the right thigh and challenged with live cells of ehrlich ascites carcinoma (EAC) in the left thigh. The expression and activity of both enzymes in the spleenocytes derived from different subjects (normal, EAC and cell lysate or cell lysate + CKI immunized mice) after cultured with EAC viable cells were determined by colorimetric assay and western blot analysis. In addition, the subjects DNA ladder and serum metalloproteases (MMP 2 and 9) zymography were observed. RESULTS: The experimental data revealed over expression of caspase3 and granzyme B in the groups of cell lysate or cell lysate + CKI immunized mice compared to control while down expression were recorded in the EAC subject. The over expression of the 2 enzymes were accompanied with increases in the activities of caspase3 and granzyme B, changes in DNA fragmentation and inhibition of metalloproteases. CONCLUSION: It could be suggested that, the parameter estimation within the present experimental framework could identify the efficiency of therapeutic vaccine protocols and elucidate the impact of CKI adjuvant with vaccines therapy.
