Influence of atorvastatin and carboxymethylated glucan on the serum lipoprotein profile and MMP activity of mice with lipemia induced by poloxamer 407

Abstract

The effects of atorvastatin and carboxymethylated β-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR male mice with acute lipemia induced with a single injection of poloxamer 407 (P-407). A novel small-angle X-ray scattering method for the determination of fractional and subfractional composition of LP-C and LP-TG was used. In P-407-treated animals, there was a drastic increase of total cholesterol and especially TG. Atorvastatin decreased both the total cholesterol and TG, but not to control levels. CMG primarily decreased TG and was not as potent as atorvastatin. P-407 increased atherogenic LDL-C (IDL-C and LDL(1-3)-C subfractions) and very low-density lipoprotein-C (VLDL-C) (VLDL(1-2)-C and VLDL(3-5)-C subfractions) fractions, with an increase of the total anti-atherogenic HDL-C fraction (HDL(2)-C subfraction). Atorvastatin treatment of lipemia was followed by a decrease in the total LP-C, total LDL-C (LDL(1-3)-C subfraction), and the LDL(1-3)-TG subfraction. Additionally, atorvastatin treatment resulted in an increase in the serum matrix metalloproteases activity both in control and P-407-treated mice. In general, high-dose atorvastatin therapy exerts its lipid-lowering and pleiotropic effects in the early stages of acute lipemia induced in mice by treatment with P-407.

Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice

“…Interestingly, the appearance of organelle-free zones and cytolysis of some hepatocytes occurred in the 1-month model, as shown in the EM study, but this was not observed after a single dose of P-407 (Korolenko et al ., 2012a). However, a common macrophage storage syndrome was observed in both models.…”

A comparative study of the hypolipidaemic effects of a new polysaccharide, mannan Candida albicans serotype A, and atorvastatin in mice with poloxamer 407-induced hyperlipidaemia

“…The main finding in this study is that mannan C. albicans serotype A functioned as an effective stimulator of murine macrophages and exerted a hypolipidaemic effect in P‐407‐induced hyperlipidaemic mice following parenteral administration. Interestingly, we have previously shown that chemically modified (partially water‐soluble) yeast polysaccharides, such as carboxymethylated β‐glucan, also exerted a hypolipidaemic effect in the P‐407‐induced hyperlipidaemic mouse model . Thus, a brief summary of our current findings using mannan C. albicans serotype A will be presented.…”

“…To determine the effects of mannans in the non‐hyperlipidaemic state, a second group of mice received mannan A in the corresponding doses and manner of administration as described above, but no P‐407 to induce hyperlipidaemia. For comparative purposes, a third group of mice was administered atorvastatin (75 mg/kg) (Atoris; KRKA, Novo mesto, Slovenia) by oral gavage at 24 and 48 h before an injection of P‐407 . Control mice received an equivalent volume (0.5 ml) of saline only.…”

“…The water‐insoluble, wall‐yeast polysaccharide known as zymosan has been shown to decrease the atherogenic serum lipids in experimental lipidaemia induced in mice, although the hypolipidaemic effects of zymosan, which is composed primarily of β‐glucan and mannan, are still poorly understood . The former component, namely β‐glucan, has previously been shown to exhibit a hypolipidaemic effect in poloxamer 407 (P‐407)‐induced hyperlipidaemic mice . Thus, besides the use of the statin class of drugs for lowering LDL cholesterol, biological response modifiers, such as the partially water‐soluble β‐1,3‐glucans, may be used as adjunctive therapy with the statins.…”

“…[6] The former component, namely b-glucan, has previously been shown to exhibit a hypolipidaemic effect in poloxamer 407 (P-407)-induced hyperlipidaemic mice. [7,8] Thus, besides the use of the statin class of drugs for lowering LDL cholesterol, biological response modifiers, such as the partially water-soluble b-1,3-glucans, may be used as adjunctive therapy with the statins. These natural polysaccharides are much less expensive than statin therapy and have no adverse side effects on the skeletal muscle.…”