Vitamin E supplementation has been shown to contribute in immunoregulation, antibody production, and resistance to implanted tumors. Similarly beta-carotene has been shown to down-regulate growth factors which contribute towards proliferation of pre-malignant cells. We embarked upon a study to evaluate the effect of vitamin E and beta-carotene on natural killer (NK) cells, which perform tumor surveillance role in the mammalian body. Mouse splenocytes or human peripheral blood lymphocytes were used as NK cells with murine YAC-1 lymphoma or human K-562 lymphoma cells, respectively, as target cells. The NK cells were treated with vitamin E or beta-carotene while target cells were labeled with sodium 51chromate. Both cell types were then reacted for 4 hours. The NK cell tumorolytic activity was measured by the chromium release assay. Oral administration of alpha-tocopherol at a dose of 100 mg/d in mice showed a significant increase in NK cell activity. Similarly, treatment of NK cells with alpha-tocopherol in vitro at doses 0.5 mg/ml, 1-0 mg/ml, and 2.0 mg/ml increased the tumorolytic activity of NK cells. Tocotrienol showed a similar response at ten times lower dose. When NK cells were treated with varying concentrations of palm vitee (mixture of alpha-tocopherol and tocotrienol), maximum effect was observed at the dose mixture of 12 micrograms and 24 micrograms alpha-tocopherol and tocotrienol, respectively. When murine NK cells were treated in vitro with beta-carotene at doses ranging from 2 ng/mg to 200 ng/ml, a decrease in tumorolytic effect was observed. However, human NK cells after treatment with beta-carotene at doses ranging from 0.1 microgram/ml to 10 micrograms/ml showed a significant increase in tumorolytic function. NK cells were also obtained from mice that had been parenterally administered beta-carotene and alpha-tocopherol. These experiments showed no significant increase in the NK cell function.
Male hamsters were fed on semi-synthetic diets containing commercial corn oil (CO), isolated corn oil triglycerides (COTG), COTG supplemented with 30 ppm of alpha-tocopherol (COTGTL) and COTG supplemented with 81 ppm of alpha-tocopherol (COTGTH) as the dietary lipid for 45 days. Male albino guinea pigs were fed on commercial chow pellets and treated with different dosages of tocopherol and tocotrienols intra-peritoneally for 6 consecutive days. Serum and liver were taken for analysis. Our results show that stripping corn oil of its unsaponifiable components resulted in COTG which yielded lower serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and raised high-density lipoprotein cholesterol (HDL-C) and serum triglycerides (TG) levels. These results indicate that the COTG with its fatty acids are responsible for the hypocholesterolemic effect exhibited by corn oil. However, supplementing the COTG diet with alpha-tocopherol (alpha-T) at 30 ppm significantly raised the serum TC, LDL-C and TG levels, but did not alter the HDL-C level, indicating that alpha-T is hypercholesterolemic. Supplementing the COTG diet with alpha-T at 81 ppm raised the serum TC level but to a lesser extent as compared to that obtained with 30-ppm alpha-T supplementation. The increased TC, in this case, was reflected mainly by an increased in HDL-C level as the LDL-C level was unchanged. The TG level was also raised but to a lesser extent than that obtained with a lower alpha-T supplementation. The liver HMG CoA reductase (HMGCR) activity was exhibited (56%) by the COTG as compared to CO. Supplementation of alpha-T at 30 ppm to the COTG diet resulted in further inhibition (76%) of the liver HMGCR activity. On the contrary, supplementation of alpha-T at 81 ppm to COTG diet resulted in a highly stimulatory effect (131%) on the liver HMGCR activity. Short-term studies with guinea pigs treated intra-peritoneally with alpha-T showed that at low dosage (5 mg) the HMGCR activity was inhibited by 46% whereas increasing the dosage of alpha-T to 20 mg yielded lesser inhibition (18%) as compared to that of the control. Further increase in the dosage of alpha-T to 50 mg actually resulted in 90% stimulation of the liver HMGCR activity as compared to the control. These results clearly indicate that the effect of alpha-T on HMGCR activity was dose-dependent. Treatment of the guinea pigs with 10 mg of tocotrienols (T3) resulted in 48% inhibition of the liver HMGCR activity. However, treatment with a mixture of 5 mg of alpha-T with 10 mg of T3 resulted in lesser inhibition (13%) of the liver HMGCR activity as compared to that obtained with 10 mg of T3. The above results indicate that the alpha-T is hypercholesterolemic in the hamster and its effect on liver HMGCR is dose-dependent. T3 exhibited inhibitory effect on liver HMGCR and alpha-T attenuated the inhibitory effect of T3 on liver HMGCR.
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