In-vivo Anti-tumor Evaluation of Dihydroartemisinin-Derived Endodisulphide on MNU-induced Liver Cancer in Sprague-Dawley Rats
Journal Title: International Journal of TROPICAL DISEASE & Health - Year 2017, Vol 25, Issue 3
Abstract
Aims: The study evaluated the antitumor potentials of a disulphide-substituted derivative of dihydroartemisinin (sDHA) on chemically induced cancer of the liver in Sprague-Dawley rats in comparison with its parent compound, dihydroartemisinin (DHA) and a standard anticancer drug. Study Design: Animals were divided into seven experimental and three control groups (n=10 per group). Cancer was induced in experimental groups followed by administration of experimental agents, while control groups received either N-methy-N-nitrosourea (MNU), Tween 80 (vehicle) or distilled water alone. Place and Duration of Study: Study was done in Faculty of Pharmacy, University of Uyo, Nigeria in 2015-2016. Methodology: MNU (50 mg/kg) was administered intravenously as single dose to induce cancer in experimental groups, followed by oral treatment with sDHA (37.42, 74.83 or 112.25 mg/kg/day), DHA (57.45, 114.89 or 172.34 mg/kg/day) or cyclophosphamide (0.71 mg/kg/day) for 28 days. Positive control group received only MNU, negative control group received only distilled water (0.3 ml/day), while experimental control group received only Tween 30 (0.3 ml/day). Drug treatments commenced 10 days after MNU injection and animals were observed for 52 days after drug treatments and sacrificed. Serum levels of CA-27-29, 8-OHdG and SOD were measured using ELISA method; and using immunohistochemical tissue staining techniques, Bcl-2 and Ki67 protein expressions were analyzed in hepatic cells. Results: MNU caused elevation (P <.0001) in CA-27-29 and 8-OHdG; and reduction (P<.0001) in SOD. Hepatic cells of MNU alone treated rats demonstrated strong immunoreactivity for Bcl-2 and Ki67 (≥75%). Oral treatments of sDHA or DHA resulted in dose-dependent reductions of MNU-induced CA-27-29 and 8-OHdG elevations (P<.001) but had no effect on SOD. Additionally, MNU induced Bcl-2 and Ki67 positive immunoreactive expressions were reduced to 25-50% by sDHA and DHA; DHA showing greater effect. Cyclophosphamide reversed all the MNU induced toxic effects. Conclusions: sDHA possesses antitumor activity against liver cancer; has lesser efficacy than DHA, but both drugs are less effective than cyclophosphamide.
Authors and Affiliations
Imoh Emmanuel Udoh, Jonah Sydney Aprioku, Iyeopu Minakiri Siminialayi
Keywords
Related Articles
- EP ID EP312744
- DOI 10.9734/IJTDH/2017/35293
- Views 56
- Downloads 0
Socio – economic Factors Influencing Utilization of Healthcare Services in Sokoto, North-Western Nigeria
The objective of equity in health care system is “equal access for equal needs” and there should be no barriers to healthcare utilization. The objective of the study was to assess the socio – economic factors influencing...
Comparative Efficacy of Amantadine Hydrochloride versus Amantadine Sulphate in Treating Egyptian Patients with Chronic HCV
Background: Pegylated interferon (peg-IFN) alpha in combination with weight-based doses of ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. However, the lo...
Age Specific Incidence of Breast Cancer in Calabar, Nigeria
Aim: To determine the incidence of breast cancer in our uncharted population with a view to determining the disease burden so as to aid planning and intervention. Study Design: A trend analysis of breast cancers in Calab...
Utilization of HIV Testing and Counseling Services by Men in the Bolgatanga Municipality
Background: In the absence of an effective vaccine and cure for Human Immunodeficiency Virus (HIV), testing and counseling for HIV remains an important intervention in the control of the infection. However, utilization o...
Schistosoma haematobium Infections: Prevalence and Morbidity Indicators in Communities around Wasai Dam, Minjibir, Kano State, Northern Nigeria
Objectives of the Study: A cross-sectional study was carried out to determine the prevalence and human risk factors of Schistosoma haematobium infections in Farawa and Koya dam-site communities in Minjibir Local Governme...