Effects of administration of α-tocopherol and tocotrienols on serum lipids and liver HMG CoA reductase activity

Abstract

Male hamsters were fed on semi-synthetic diets containing commercial corn oil(CO), isolated corn oil triglycerides (COTG), COTG supplemented with 30 ppm ofα-tocopherol (COTGTL) and COTG supplemented with 81 ppm of α-tocopherol(COTGTH) as the dietary lipid for 45 days. Male albino guinea pigs were fed oncommercial chow pellets and treated with different dosages of tocopherol andtocotrienols intra-peritoneally for 6 consecutive days. Serum and liver were takenfor analysis. Our results show that stripping corn oil of its unsaponifiablecomponents resulted in COTG which yielded lower serum total cholesterol (TC)and low-density lipoprotein cholesterol (LDL-C) and raised high-density lipoproteincholesterol (HDL-C) and serum triglycerides (TG) levels. These results indicate thatthe COTG with its fatty acids are responsible for the hypocholesterolemic effectexhibited by corn oil. However, supplementing the COTG diet with α-tocopherol(α-T) at 30 ppm significantly raised the serum TC, LDL-C and TG levels, but didnot alter the HDL-C level, indicating that a-T is hypercholesterolemic. Supplementingthe COTG diet with α-T at 81 ppm raised the serum TC level but to a lesserextent as compared to that obtained with 30-ppm α-T supplementation. Theincreased TC, in this case, was reflected mainly by an increased in HDL-C level asthe LDL-C level was unchanged. The TG level was also raised but to a lesser extentthan that obtained with a lower α-T supplementation. The liver HMG CoAreductase (HMGCR) activity was exhibited (56%) by the COTG as compared toCO. Supplementation of α-T at 30 ppm to the COTG diet resulted in furtherinhibition (76%) of the liver HMGCR activity. On the contrary, supplementation ofα-T at 81 ppm to COTG diet resulted in a highly stimulatory effect (131%) on theliver HMGCR activity. Short-term studies with guinea pigs treated intra-peritoneallywith α-T showed that at low dosage (5mg) the HMGCR activity was inhibited by46% whereas increasing the dosage of α-T to 20 mg yielded lesser inhibition (18%)as compared to that of the control. Further increase in the dosage of α-T to 50 mgactually resulted in 90% stimulation of the liver HMGCR activity as compared tothe control. These results clearly indicate that the effect of α-T on HMGCR activitywas 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 amixture of 5 mg of α-T with 10 mg of T3 resulted in lesser inhibition (13%) of theliver HMGCR activity as compared to that obtained with 10mg of T3. The aboveresults indicate that the α-T is hypercholesterolemic in the hamster and its effect onliver HMGCR is dose-dependent. T3 exhibited inhibitory effect on liver HMGCRand α-T attenuated the inhibitory effect of T3 on liver HMGCR.