Study of Colonic Cell Proliferation Induced by Chronic Toxicity of Orlistat and The Possible Protective Effect of Ginseng in Experimental Animals

Document Type : Original Article

Authors

1 Department of Forensic Medicine & Toxicology , Faculty of Medicine , Minia University, Egypt

2 Departments of Histology, Faculty of Medicine, Minia University, Egypt

Abstract

Orlistat is a widely used anti-obesity agent available as a Mn-prescription medicatio11 in many devel
oped countries. Its long term use may result in an increasing frequency of chronic toxicity. This work was
designed to clarify the effect of Orlist.at on the colonic cell proliferation and the formation of colonic
aberrant crypt foci ( ACF) and to investigate the possible ameliorating effect of Ginseng in experimemal animals. Eighty adult male albiM rats were used in this work; group J (control g:oup) received a stan
dard diet. Group II (Ginsertg group) fed on diet containing lo/o red Ginseng. Group lll (high fat diet
group, HFD)fed onlO% corn-oil enriched diet. Group IV (Or/is tat group) received oral Orlistat (125 mg
I kg I day), group V (Orlistat + HFD group). Group VI (HFD + Ginseng group). Group VII (Or/istat + Ginseng group) and lastly group VII! (Orlistat + HFD + Ginseng group). After 16 weeks, animals were
sacrificed and their colons were immunostained using proliferating cell n.uclear antigen (PCNA) as a
marker of cell proliferation which is the biomarker of increased susceptibility to gastrointestinal cancer.
Results showed that Orlistat and/ or HFD resulted in increased immuMlabelling for PCNA causing a
statistically significant increase in PCNA-labelling Index (PCNA-LI) when compared with the control groups. Ginseng when combined with Orlistat or HFD or Orlistat + HFD caused a significant decrease
of both the immu110labelling and PCNA-Ll. Consequently, it has been proposed to clarify the long-term
impact of Orlistat treatment for physicians working in this field and for the public by the drug brochure.
Also, Ginseng should be given with Orlistat as a protective agent to ameliorate its proliferative effect on
the colonic mucosa.