Suppression of 7,12-dimethylbenz[alpha]anthracene-induced carcinogenesis and hypercholesterolaemia in rats by tocotrienol-rich fraction isolated from rice bran oil.
The anti-tumour and anti-cholesterol impacts of tocotrienol-rich fraction (TRF) were investigated in rats treated with the chemical carcinogen 7,12-dimethylbenz [alpha]anthracene (DMBA), which is known to induce mammary carcinogenesis and hypercholesterolaemia. DMBA administration to rats was associated with the appearance of multiple tumours on mammary glands after 6 months. Alkaline phosphatase (ALP) and glutathione-S-transferase (GST) are used as marker enzymes to monitor the severity of carcinogenesis. Although no tumours were visible on livers, hepatic ALP and GST activities of DMBA-treated rats were profoundly elevated in comparison to enzyme activities of normal control rats. Feeding of TRF (10 mg/kg body weight/day) for 6 months, isolated from rice bran oil (RBO), to DMBA-administered rats, reduced the severity and extent of neoplastic transformation in the mammary glands. Similarly, plasma and mammary ALP activities increased during carcinogenesis (95% and 43%, respectively), were significantly decreased in TRF-treated rats, whereas TRF mediated a further increase of 51% in hepatic ALP activity. TRF treatment to rats maintained low levels of GST activities in liver ( approximately 32%) and mammary glands ( approximately 21%), which is consistent with anti-carcinogenic properties of TRF. Administration of DMBA also caused a significant increase of 30% in plasma total cholesterol and 111% in LDL-cholesterol levels compared with normal control levels. Feeding of TRF to rats caused a significant decline of 30% in total cholesterol and 67% in LDL-cholesterol levels compared with the DMBA-administered rats. The experimental hypercholesterolaemia caused a significant increase in enzymatic activity (23%) and protein mass (28%) of hepatic 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase. Consistent with TRF-mediated reduction in plasma lipid levels, enzymatic activity and protein mass of HMG-CoA reductase was significantly reduced. These results indicate that TRF has potent anti-cancer and anti-cholesterol effects in rats.
Iqbal
J
J
Anatomy and Cell Biology, Box No. 5, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY-11203, USA. jahangir.iqbal@downstate.edu
Minhajuddin
M
M
Beg
Z H
ZH
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000214:Acyl Coenzyme A / Q000494:pharmacology; D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic; D002784:Cholesterol / Q000032:analysis; D005260:Female; D005982:Glutathione Transferase / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000150:complications*; D008099:Liver / Q000737:chemistry; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis / Q000517:prevention & control; D010938:Plant Oils / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000073879:Rice Bran Oil; D024508:Tocotrienols / Q000008:administration & dosage / Q000494:pharmacology*
D000214:Acyl Coenzyme A; D000975:Antioxidants; D002273:Carcinogens; D010938:Plant Oils; D024508:Tocotrienols; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D015127:9,10-Dimethyl-1,2-benzanthracene; D002784:Cholesterol; D005982:Glutathione Transferase; D000469:Alkaline Phosphatase; D000073879:Rice Bran Oil