Deep glance on the antiparasitic anticancer activities of wheat germ oil in chronically infected immunosuppressed mice with cryptosporidiosis

Abstract

Cryptosporidium species are the major cause of water-borne epidemics of diarrhea in both developing and developed countries that vary from self-limited in immunocompetent patients to severe life-threatening in the immunocompromised hosts. There was a proven correlation between cryptosporidiosis and colorectal cancers, although, studies in this field are still limited. Wheat germ oil (WGO) is a natural product with a known antiparasitic effect and potential antiproliferative activities. This study aimed to evaluate the antiparasitic and anticancer activities of WGO in chronically infected immunosuppressed mice compared to Nitazoxanide (NTZ). This experimental case-control study was performed in the period from January till September 2021. Eighty immunosuppressed bred laboratory mice were divided into 4 groups, 20 mice each; GI non-infected; negative control (NC), GII infected non treated; positive control (PC), GII infected, and treated with NTZ, GIV infected, and treated with WGO. Parasitological, histopathological, and immunohistochemical examinations were performed with estimating the rate of maximal survival for the study groups. Parasitological examination revealed a marked reduction in the mean Cryptosporidium spp. oocyst counts in the stool of GIV compared to PC, and GIII (P-value < 0.001). Histopathological and immunohistochemical examinations showed the best results with GIV which revealed restoration of normal villous pattern, with no dysplasia or malignancy could be detected. GIV showed the best survival rate compared to PC and GIII. WGO is an extremely promising agent that has an excellent therapeutic effect against cryptosporidiosis with the ability to control the tumorigenesis process in the chronically infected immunosuppressed hosts.

Keywords: Cryptosporidiosis; Histopathology; Immunohistochemistry; Nitazoxanide; Wheat germ oil.

Fig. 1

a Section from the ileocaecal region of GI showing mild inflammation (red arrow) and minimal superficial erosions (blue arrow) (H&E stain, X200), b Sections in intestine of GI showing remarkable nuclear positivity for CDX2 (IHC for CDX2, X400) c Sections in intestine of GI showing faint cytoplasmic positivity for Caspase-3 in crypt cells (red arrow) (IHC for Caspase-3, X400) (color figure online)

Fig. 2

a Ileocecal sections of GII showing villous shortening (red line), broadening (blue line) and villous tip erosions (yellow arrow), moderate inflammation (green arrow) (H&E stain X100), b Section in ileocecal region of GII showing many oocysts (red arrows) adherent to the surface of epithelial cells, (H&E stain, X1000), c Sections in ileocecal region of GII showing focal low-grade dysplasia (red arrow) with mucin depletion (H&E stain, X200), d Section of GII showing nearly negative nuclear positivity for CDX2 (IHC for CDX2, X400) e Intestinal section of GII showing high percentage of dense cytoplasmic positivity for Caspase 3 (arrows) (IHC for Caspase-3, X400) (color figure online)

Fig. 3

a Section in ileocecal region of mice of GIII showing less inflammation, more villous preservation, and minute ulcerations. No dysplasia or malignancy could be detected within examined sections. (H&E stain, X200), b Intestinal section of GIII showing moderate nuclear positivity for CDX2 (red arrow) (IHC for CDX2, X400), c Sections in intestine of GIII showing few scattered cytoplasmic positivity for Caspase-3 (red arrows) (IHC for Caspase-3, X400) (color figure online)

Fig. 4

a Sections of ileocecal region of GIV mice showing mild inflammation, villous preservation, and minute erosions (red arrow). No dysplasia or malignancy could be detected. (H&E stain, X200), b Sections in intestinal of GIV showing high nuclear positivity for CDX2 (red arrows) (IHC for CDX2, X400), c Intestinal section of GIV showing negative cytoplasmic positivity for Caspase-3 (IHC for Caspase-3, X400) (color figure online)

Fig. 5

Mean survival time for the study groups (days)