Effect of Diethylcarbamazine Citrate and Setaria equina Excretory–Secretory Material on Rat Hepatocellular Carcinoma

Abstract

Diethylcarbamazine citrate (DEC) has been known for its efficacy to eradicate bancroftian filariasis in Egypt and other countries in the world. One of the known effects was to decrease the level of circulating filarial antigen in the patient's serum. The target of this study was to examine the effect of DEC, excretory-secretory (ES) material from the filarial parasite Setaria equina or a combination of both on the status of oxidative stress and pathogenesis of rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine and 2-acetylaminofluorene. This could be tested in vitro using nitroblue tetrazolium reduction test for measuring the level of superoxide anion (O₂(•-)) released from rat peritoneal macrophages. For in vivo test, a single dose before induction of carcinogenesis or continually repeated doses with DEC, ES or DEC + ES was used. Exposure of macrophages to ES could lead to a significant decrease (p < 0.01) in O₂(•-) release, while DEC (200 μM) could modulate such effect with significant increase (p < 0.05). Pathogenesis of liver cancer and treatment were evaluated using histological investigation, level of antioxidant and liver function enzymes. Repeated ES doses could increase the activity of antioxidant enzymes, especially the catalase enzyme and show a protective effect on liver architecture. DEC could modulate the later effects when combined with ES. No significant effect on the liver function enzymes after treatment was observed. Nuclear factor κB was found to be localized only in the cytoplasm after single and repeated treatments with ES. This study could indicate the effect of S. equina ES as antioxidant against rat HCC, while DEC could modulate such effect when combined with it.

Identification of the complement 9‐binding protein in Setaria equina excretory‐secretory products

“…Previously, repeated doses of SeqES in experimentally induced hepatocarcinogenesis could show some of the protective effects as a result of reduced inflammatory responses and oxidative stress . One of those anti‐inflammatory effects was the inhibition of complement activation.…”

“…The anti‐inflammatory properties of ES products could be applied for protection against inflammatory diseases like rheumatoid arthritis . Our previous studies for the SeqES immunomodulatory effect indicated downregulation of macrophage activity, IFN‐γ production by peripheral blood mononuclear cells (PBMCs) and complement activation (CH 50 ) . This, in turn, indicated the existence of complement‐binding or inhibitory protein.…”