Elevation of serum cholesterol levels in mice by the antioxidant butylated hydroxyanisole

Abstract

The food antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are structurally related to the hypocholesterolemic drug probucol. The purpose of this study was to determine if BHA can lower serum cholesterol levels as is observed with probucol. Treatment of mice with 0.75% BHA in their feed for 10 days resulted in a significant (P ≤ 0.01) elevation of serum cholesterol levels. This effect contrasts with the cholesterol-lowering effect of probucol. Further, the degree of cholesterol elevation was comparable to that observed in mice administered 3% cholesterol in their feed for 7 days. The enzyme acyi CoA: cholesterol acyltransferase (ACAT) was decreased significantly (P ≤ 0.01) in liver microsomes from BHA-treated mice. In contrast, hepatic microsomal ACAT activity was increased significantly (P ≤ 0.01) in cholesterol-fed mice. These results suggested that the increased serum cholesterol observed in BHA-treated mice was not accompanied by an increase in hepatic cholesterol levels. Indeed, hepatic microsomal cholesterol levels were reduced in BHA-treated mice, but were increased significantly (P ≤ 0.01) in cholesterol-fed mice. These results demonstrate that the common food additive BHA elevates serum cholesterol levels by a mechanism that apparently involves the decreased uptake of cholesterol by the liver.