Studies on Parasitologic and Haematologic Activities of an Enaminone Derivative of 4-Hydroxyquinolin-2(1H)-one Against Murine Schistosomiasis Mansoni

Amal M. El–Shennawy, MD; Amira H. Mohamed, MD; Mohamed Abass, MD

Disclosures
In This Article

Results

All the mice survived in good health without weight loss until the end of the experiment.

Parasitologic Study ( Table 1 and Table 2 )

PZQ–and BDHQ–treated groups caused highly significant reductions (P < .001) in mature worm loads and tissue egg loads compared with control, while BDHQ–treated groups only showed significant reductions in immature worm compared with control and PZQ–treated groups (P < .05). The group treated with a higher dose showed significant reductions in intestinal ova count compared with the PZQ–treated group (P < .05).

IFN–gamma and Anti–SWAP IgE ( Table 3 , Figures 1 and 2)

On comparison of BDHQ with other groups, we found a significant increase in serum levels of IFN–gamma compared with controls (P < .05), and the difference between the BDHQ– and PZQ–treated groups was nonsignificant. With regard to anti–SWAP IgE, a significant increase was observed compared with controls and PZQ–treated groups (P < .05).

Figure 2.

Serum levels of anti–SWAP IgE in Schistosoma mansoni–infected mice treated with BDHQ at 2 different doses and praziquantel compared with infected untreated controls.

Ultrastructural Study

Worms. Ultrastructural examination of the worms revealed detachment and implantation of the spines within vesiculated and degenerated tegument in all treated groups in comparison to untreated groups (Figures 3–6), while the genital system was affected in the BDHQ–treated group only in the form of pycnosis of germinal vesicles of the oocytes and necrosis of the follicular epithelium in female worms (Figure 7) and necrosis of spermatocyte in male worms (Figure 8).

Figure 3.

Electron micrograph of the tegument of untreated Schistosoma mansoni showing the pointed spines (S) (X 2000).

Figure 4.

Electron micrograph of the tegument of BDHQ–treated Schistosoma mansoni showing complete detachment of the spines (S) (X2000).

Figure 5.

Electron micrograph of BDHQ–treated Schistosoma mansoni worm showing implantation of the spines within vesiculated tegument (T) (X 3000).

Figure 6.

Electron micrograph of praziquantel–treated Schistosoma mansoni worm showing detachment of one spine (Sd) and implantation of the other (Si) within severely vesiculated tegument (T) (X 3000).

Figure 7.

Electron micrograph of BDHQ–treated female Schistosoma mansoni worm showing pycnosis of germinal vesicles of all the oocytes and necrosis of follicular epithelium of the left one (FEd) (X 3000).

Figure 8.

Electron micrograph of BDHQ–treated male Schistosoma mansoni worm showing vaculation and necrosis of spermatocyte (S) (X 5000).

Buffy Coat, Bone Marrow, Liver, and Spleen. Ultrastructural examination showed evidence of cellular activation in the buffy coat and liver in both BDHQ– and PZQ–treated groups in comparison to untreated groups, while in the bone marrow and spleen, the evidence of cellular activation was remarkable in BDHQ–treated groups. In buffy coat examination of all treated groups, monocytes revealed evidence of activation represented by a large number of extending pseudopodia (Figure 9) and the activation of lymphocytes represented by thinly distributed chromatin in most parts of the nucleus, vacuolization of the cytoplasm, and a large number of mitochondria (Figure 10). Bone marrow examination showed evidence of promonocyte activation in BDHQ–treated groups (Figure 11), while eosinophil activation could be detected in all treated groups (Figures 12 and 13). Evidence of lymphocyte activation was observed in both PZQ–and BDHQ–treated livers (Figure 14 and 15). Spleen examination in BDHQ–treated groups showed increases in follicular dendritic cells –– with irregular nucleus that was poor in heterochromatin and thin sheets of cytoplasmic extensions –– and their intimate contact with the lymphocytes could be observed (Figure 16). Remarkable increases in longitudinal intracellular contractile filaments in the endothelial cells lining the splenic sinus and its fenestration could be observed (Figure 17).

Figure 9.

Electron micrograph of 2 monocytes in the peripheral blood of BDHQ–treated mouse revealed evidence of activation represented by large number of extending pseudopodia (x 2500).

Figure 10.

Electron micrograph of activated lymphocyte in the peripheral blood of praziquantel–treated mouse. The cell is characterized by thinly distributed chromatin in most parts of the nucleus (arrow), vacuolization of the cytoplasm (V), and a large number of mitochondria (M) (x 2500.)

Figure 11.

Electron micrograph of a promonocyte in bone marrow of BDHQ–treated mouse. The nucleus has fine chromatin and is situated at one end of the cell. Bundles of filaments are prominent in the cytoplasm, which are presumably related to its property of motility and active endocytosis (X 3600).

Figure 12.

High magnification showing the process of discharge of the eosinophilic granules in the bone marrow of a mouse treated with praziquantel (x 8000).

Figure 13.

Electron micrograph of degranulated eosinophil in the bone marrow of BDHQ–treated mouse (x 4500).

Figure 14.

Ultrastructure of 3 activated lymphocytes characterized by thinly distributed chromatin in the liver of Schistosoma mansoni–infected mouse treated with praziquantel; they are in intimate contact and the left one is in mitosis (X 4000).

Figure 15.

Ultrastructure of activated lymphocyte (plasmablast) in intimate contact with the fibroblast in the liver of Schistosoma mansoni–infected mouse treated with BDHQ. The plasmablast shows a round and small eccentric nucleus in relation to the cell size. The cytoplasm is filled with dilated endoplasmic reticulum (ER) and a few remaining free ribosomes (R). (X 5000)

Figure 16.

Electron micrographs of spleen of BDHQ–treated mouse showing the tightly packed lymphocytes in the central area of the periarteriolar lymphatic sheath (PALS); they are in intimate contact with the interdigitating cells (I). Junction between follicular dendritic cell (FDC), with irregular nucleus that is poor in heterochromatin and thin–sheet cytoplasmic extensions, and 2 lymphocytes (L) were detected (X 1800).

Figure 17.

Longitudinal section of the splenic sinus (S.S.) in BDHQ–treated mouse showing the increase of longitudinal intracellular contractile filaments (arrow) in the endothelial cells lining the splenic sinus; fenestration of the sinus (F) could be observed. Follicular dendritic cells (FDC) are sending thin–sheet cytoplasmic extensions (c) to the adjacent activated lymphocyte (L) that is going to enter into the sinus (X 1800).

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