Hypocholesterolemic drug

The statin family of six closely related hypocholesterolemic drugs are all potent competitive inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase), the rate-limiting enzyme in cholesterol biosynthesis. The liver is their target organ, and decreased hepatic cholesterol synthesis ultimately leads to increased removal of LDL particles from the circulation. As a consequence, all other hypocholesterolemic drugs have been relegated to secondary status. 

Probucol (Lorelco) is a hypocholesterolemic drug with few side effects that modestly (15-30%) decreases elevated plasma LDL cholesterol levels. The marginal... 

LDL-lowering action plus reports that it can lower HDL cholesterol resulted in its discontinuation as a hypocholesterolemic drug. However, it still may reduce the risk of CHD because it is a powerful antioxidant. 

Probucol, a hypocholesterolemic drug that possesses antioxidant activity, inhibits the ex vivo release of IL-1 from LPS-stimulated macrophages of mice pretreated orally with 100 mg/kg/day of this compound [94,95]. This compound has been shown to inhibit LPS-induced zinc-lowering effect, is cited as direct evidence for the inhibition of IL-1 release, and may be useful candidate for the treatment of atherosclerosis [95,96]. An amino-dithiol-one derivative (RP 54745) blocked the proliferative action of IL-1 P on murine thymocytes in vitro and also inhibited the production of IL-1 in mouse peritoneal macrophages in vitro and in vivo. The compound RP 54745 selectively inhibited the expression of IL-la and IL-1 3 mRNA while TNFa mRNA was unaffected [97, 98]. 

As summarized in the previous paragraph, LDL cholesterol is oxidized to various oxysterols due with high cytotoxicity and promoting vascular injury [63]. Oleuropein and a mixture of phenols extracted from virgin oil inhibited dose-dependently the formation of oxysterols and prevented apoprotein modification in UV irradiated LDL. IC50 are shown in table 4 results indicate that the mixture is more potent than the single compounds and probucol, a hypocholesterolemic drug with well-known antioxidant activity. As expected the contribution of tyrosol to the antioxidant effect was minimal [71]. 

Cendella RJ. Cholesterol and hypocholesterolemic drugs. In Craig CR, Stitzel RE, eds. Modern Pharmacology with Clinical Applications, 5th Ed. Boston Little, Brown and Co., 1997 279-289. 

Kobayashi et al (16), compared the effectiveness of chitosan with konjac flour and two hypocholesterolemic drugs. Their experiment included one week feeding of cholesterol-containing diet to rats with 4% level of test materials. 

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