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  1. Mohamed J, Wei WL, Husin NN, Alwahaibi NY, Budin SB
    Pak J Biol Sci, 2011 Dec 01;14(23):1055-60.
    PMID: 22590839
    Selenium in the form of sodium selenite (SSE) is an essential micronutrient which known to possess antioxidant and anticancer properties. This study emphasizes the role of selenium on oxidative stress in experimental rats with N-diethylnitrosamine (DEN) initiated and 2-acetylaminofluorene (2-AAF) promoted multistage hepatocellular carcinogenesis (HCC). Rats were divided randomly into six groups: negative control, positive control (DEN+2-AAF), preventive group (pre-SEE 4 weeks+DEN), preventive control (respective control for preventive group), therapeutic group (DEN+post-SSE 12 weeks) and therapeutic control (respective control for therapeutic group). SSE (4 mg L(-1)) was given to animals before initiation and during promotion phase of HCC. The levels of total protein (TP), conjugated diens (CD), malondialdehyde (MDA), fluorescent pigment (FP), antioxidant activity (AOA) and DNA damage were measured. Supplementation of SSE before the initiation phase of carcinogenicity significantly increased TP and AOA level (p < 0.05) while it decreased the levels of CD, MDA, DNA damage and FP (p < 0.05). Supplementation of SSE during the promotion phase of carcinogenicity significantly decreased the DNA damage and FP level (p < 0.05) and there were negative correlation between the level of AOA and with the level of FP and CD. Thus, supplementation of SSE reduced the adverse changes which occur in liver cancer. However, the chemoprevention effect of SSE was more pronounced when it was supplemented before initiation phase of cancer when compared to promotion phase.
    Matched MeSH terms: Liver Neoplasms, Experimental/metabolism
  2. Shamaan NA, Kadir KA, Rahmat A, Ngah WZ
    Nutrition, 1998 12 3;14(11-12):846-52.
    PMID: 9834927
    The effects of vitamin C and aloe vera gel extract supplementation on induced hepatocarcinogenesis in male Sprague-Dawley rats (120-150 g) by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) was investigated. The severity of the carcinogenesis process was determined by measuring gamma-glutamyl transpeptidase (GGT) and the placental form of glutathione S-transferase (GSTP) histochemically in situ and in plasma and liver fractions. In addition, plasma alkaline phosphatase (ALP) and liver microsomal uridine diphosphate glucuronyl transferase (UDPGT) activity were also determined. Administration of DEN/AAF caused an increase in the surface area and number of enzyme-positive foci (both GGT and GSTP) compared with control. Supplementation of vitamin C or aloe vera gel extract to the cancer-induced rats suppressed this increase significantly (P < 0.05; P < 0.001). Increases in liver UDPGT, GGT, and GSTP activities were also observed with cancer induction that were again suppressed with either vitamin C or aloe vera gel supplementation. Plasma GGT in the DEN/AAF rats were determined monthly for the duration of the experiment and found to be reduced as early as 1 mo with aloe vera gel supplementation and 2 mo with vitamin C supplementation. In conclusion, vitamin C and aloe vera gel extract supplementation were found to be able to reduce the severity of chemical hepatocarcinogenesis.
    Matched MeSH terms: Liver Neoplasms, Experimental/metabolism
  3. Hambali Z, Ngah WZ, Wahid SA, Kadir KA
    Pathology, 1995 Jan;27(1):30-5.
    PMID: 7603748
    The effects of ovariectomy and hormone replacement in control and carcinogen treated female rats were investigated by measuring whole blood and liver glutathione (WGSH, HGSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GRx) and histological evaluation. Hepatocarcinogenesis was induced by diethylnitrosamine and 2-acetylaminofluorene. In control rats not receiving carcinogen, ovariectomy significantly increased the GST and GRx activities. Replacement with either estrogen or progesterone reduced the GST activities to below intact female values whereas replacement of both hormones together brought the GST activities to that of intact females. GRx activities were brought to intact female values by replacement with estrogen or progesterone, either singly or in combination. Neither ovariectomy nor sex hormone/s replacement influenced the levels of WGSH, HGSH and GPx activities. Carcinogen administration to intact rats increased all the parameters measured. Ovariectomized rats treated with carcinogen showed lower GPx and GRx activities at 2 mths. However, replacement with either progesterone or combined estrogen and progesterone increased GPx and GRx activities to original values. On the other hand GST and GPx activities in ovariectomized rats which had carcinogen treatment were lower than intact rats after 5 mths. Replacement with hormones either singly or both brought GST and GPx activities up to intact rat levels receiving carcinogen. The levels of WGSH, HGSH and GRx activities (5 mths) in carcinogen treated rats were not influenced by ovariectomy and/or hormone/s replacement. The results from this study suggested that ovariectomy reduced the severity of hepatocarcinogenesis which was restored by sex hormone/s replacement.
    Matched MeSH terms: Liver Neoplasms, Experimental/metabolism
  4. Habib SH, Makpol S, Abdul Hamid NA, Das S, Ngah WZ, Yusof YA
    Clinics (Sao Paulo), 2008 Dec;63(6):807-13.
    PMID: 19061005
    OBJECTIVE: To evaluate the effect of ginger extract on the expression of NFkappaB and TNF-alpha in liver cancer-induced rats.

    METHODS: Male Wistar rats were randomly divided into 5 groups based on diet: i) control (given normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline-deficient diet + 0.1% ethionine to induce liver cancer and v) choline-deficient diet + ginger extract (100mg/kg body weight). Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFkappaB and TNF-alpha.

    RESULTS: The expression of NFkappaB was detected in the choline-deficient diet group, with 88.3 +/- 1.83% of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFkappaB was significantly reduced, to 32.35 +/- 1.34% (p<0.05). In the choline-deficient diet group, 83.3 +/- 4.52% of samples showed positive staining of TNF-alpha, which was significantly reduced to 7.94 +/- 1.32% (p<0.05) when treated with ginger. There was a significant correlation demonstrated between NFkappaB and TNF-alpha in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group.

    CONCLUSION: In conclusion, ginger extract significantly reduced the elevated expression of NFkappaB and TNF-alpha in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFkappaB through the suppression of the pro-inflammatory TNF-alpha.

    Matched MeSH terms: Liver Neoplasms, Experimental/metabolism
  5. Alwahaibi NY, Budin SB, Mohamed J, Alhamdani A
    J Gastroenterol Hepatol, 2010 Apr;25(4):786-91.
    PMID: 20492335 DOI: 10.1111/j.1440-1746.2009.06160.x
    Selenium's molecular mechanism for cancer chemoprevention remains unknown. We aimed to study the gene expression of nuclear factor-kappaB (NF-kappaB), tumor growth factor-alpha (TGF-alpha) and cyclin D1 and the effects of sodium selenite using preventive and therapeutic approaches in chemically-induced hepatocarcinogenesis in rats.
    Matched MeSH terms: Liver Neoplasms, Experimental/metabolism
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