Cholesterol-induced Atherosclerosis In Rabbits Research Articles

Lp-PLA2 (Lipoprotein-Associated Phospholipase A2) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits.

Elevated plasma Lp-PLA2 (lipoprotein-associated phospholipase A2) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA2 is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA2 could be a potential preventative target of atherosclerosis, we generated Lp-PLA2 knockout rabbits and investigated the pathophysiological functions of Lp-PLA2. Lp-PLA2 knockout rabbits were generated using CRISPR/Cas9 system to assess the role of Lp-PLA2 in plasma lipids regulation and identify its underlying molecular mechanisms. Homozygous knockout rabbits along with wild-type rabbits were fed a cholesterol-rich diet for up to 14 weeks and their atherosclerotic lesions were compared. Moreover, the effects of Lp-PLA2 deficiency on the key cellular behaviors in atherosclerosis were assessed in vitro. When rabbits were fed a standard diet, Lp-PLA2 deficiency led to a significant reduction in plasma lipids. The decreased protein levels of SREBP2 (sterol regulatory element-binding protein 2) and HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) in livers of homozygous knockout rabbits indicated that the cholesterol biosynthetic pathway was impaired with Lp-PLA2 deficiency. In vitro experiments further demonstrated that intracellular Lp-PLA2 efficiently enhanced SREBP2-related cholesterol biosynthesis signaling independently of INSIGs (insulin-induced genes). When fed a cholesterol-rich diet, homozygous knockout rabbits exhibited consistently lower level of hypercholesterolemia, and their aortic atherosclerosis lesions were significantly reduced by 60.2% compared with those of wild-type rabbits. The lesions of homozygous knockout rabbits were characterized by reduced macrophages and the expression of inflammatory cytokines. Macrophages of homozygous knockout rabbits were insensitive to M1 polarization and showed reduced DiI-labeled lipoprotein uptake capacity compared with wild-type macrophages. Lp-PLA2 deficiency also inhibited the adhesion between monocytes and endothelial cells. These results demonstrate that Lp-PLA2 plays a causal role in regulating blood lipid homeostasis and Lp-PLA2 deficiency protects against dietary cholesterol-induced atherosclerosis in rabbits. Lp-PLA2 could be a potential target for the prevention of atherosclerosis.

Beneficial Effects of L-carnitine on Cholesterol-Induced Atherosclerosis in Rabbits: An Animal Model Study

Twenty five rabbits were randomized into five groups (n = 5): Normal Control group(NC) were kept on a plain chow diet for 75 days. AT group were kept on a hypercholesterolaemicdiet for 75 days. ATO (atorvastatin) group were fed the same diet and receivedatorvastatin orally (20mg/kg/day) from day 45 for 30 days. L group were fed thesame diet and intraperitoneal L-carnitine (250 mg/kg/day) from day 45 for 30 days (completionof treatment). ATO/L group were fed the same diet and atorvastatin orally(l0 mg/kg/day) and L-carnitine intraperitoneally (125 mg/kg/day) from day 45 for 30 days.Histopathological investigations of aorta and assessment of serum profile were carried out to determine Blood urea nitrogen (BUN), creatinine (Cr), Sodium (Na), potassium (K), Phosphorus (P), triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Alkaline phosphatase(ALK). The aorta wall of hypercholesterolaemic rabbits showedfoam cells with disrupted endothelial lining and changed muscle fibers. The animals of ATO and ATO/L groups had normal aorta wall. TG significantly increased in hypercholesterolaemic rabbits.L-carnitine treatment significantly reduced TG (P 0.05) except for L group, where BUN level wassignificantly higherthan those in ATO and ATO/L groups (P<0.05). Serum AST, ALT and ALK levels were significantly reduced in L-carnitine treated animals compared to ATO group (P<0.05). L-carnitine prevented progression of atherosclerotic lesions.

Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence.

L-citrulline and L-arginine supplementation has been shown to have several beneficial effects on the cardiovascular system. Nitric oxide (NO) protects against the progression of atherosclerosis and is synthesized by nitric oxide synthase (NOS), which converts L-arginine (L-Arg) into L-citrulline (L-Cit). Our previous study revealed that chronic administration of a combination of L-Cit and L- Arg has a better therapeutic effect on high cholesterol-induced atherosclerosis in rabbits. We investigated how L-Arg and L-Cit affect endothelial function, aging and atherosclerosis. Following a 3-day stimulation of human umbilical venous endothelial cells (HUVECs) with high glucose (HG: 22 mM) and L-Arg (300 μM), L-Cit (300 μM) or L-Arg plus L-Cit (LALC: each 150 μM) supplementation, endothelial senescence and function were evaluated. These amino acids were also administered to dyslipidemic type 2 diabetic (ZDFM) rats fed a high cholesterol diet. They were fed L-Arg or L-Cit or LALC for four weeks. Aortic senescence was investigated by measuring senescence-associated ß-galactosidase (SA-ß-gal), telomerase activity, DNA damage and p16INK4a protein expression. Only L-Cit and LALC supplementation retarded the HG-induced endothelial senescence, as evaluated by SA-ß-gal activity, a widely used marker of cellular senescence, p16INK4a expression, a senescence-related protein, and DNA damage. Under HG conditions, L-Cit and LCLA restored telomerase activity to levels observed under normal glucose (NG) conditions. Under HG conditions, L-Cit decreased ROS production, as measured by CM-H2DCFDA and the expression of p67phox, a major component of NADPH oxidase. Under HG conditions, L-Cit and LALC increased NO production, as measured by DAF-2AM. Endothelial NO synthase (eNOS) and phosphorylated eNOS were decreased under HG conditions and L-Cit and LALC significantly increased these levels. Arginase 2 protein expression increased under the HG conditions, and L-Cit and LALC significantly attenuated this effect. In ZDFM rats, SA-ß-gal activity was detected on the aortic endothelial surface; however, L-Cit and LALC reduced these levels. L-Cit and LALC both decreased the proportion of senescent cells. Furthermore, treatment with LALC for 4 weeks increased plasma NO production. Therefore conclusively, L-citrulline supplementation rescued NO levels better than L-arginine supplementation by inhibiting ROS production and arginase 2 protein expression. Consequently, L-Cit and LCLA supplementation retaeded HG-induced endothelial senescence.

Rapamune does not attenuate high cholesterol-induced atherosclerosis in rabbits.

Solid-organ transplant recipients are prone to develop atherosclerosis. The objectives of this study were to investigate the effects of Rapamune (Wyeth Canada, Saint-Larent, QC, Canada) on the rabbit model of atherosclerosis. The rabbits were assigned to four groups: group I, regular diet (control); group II, 1% cholesterol diet; group III, control with Rapamune (1 mg/kg/d orally); and group IV, high cholesterol diet with Rapamune. Blood samples for serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C]), as well as malondialdehyde, and protein carbonyls, the indices of oxidative stress were collected at the end of 2 months on the respective diet regimen. Aortic tissue for atherosclerotic changes were also collected for oxidative stress indices were also collected. Rapamune reduced serum levels of TG, TC, LDL-C, and HDL-C. Rapamune elevated the oxidative stress in rabbits on high cholesterol diet. Rapamune did not attenuate extent of atherosclerosis (group II vs. group IV, 45.00 ± 12.00 vs. 57.28 ± 2.99%); intimal thickness (group II vs. group IV, 32.38 ± 7.14 × 10(3) vs. 21.90 ± 11.98 × 10(3) μm(2)); intimal/medial ratio (group II vs. group IV, 0.50 ± 0.06 vs. 0.35 ± 0.06); and macrophage accumulation (group II vs. group IV, 69.72 ± 5.02 vs. 61.52 ± 8.94%) in the intima of rabbits on high cholesterol diet. The data suggest that (1) Rapamune increased the oxidative stress in rabbits on high cholesterol diet and (2) Rapamune did not attenuate the hypercholesterolemic atherosclerosis in the rabbit model.

Antimutagenic and some other effects of conjugated linoleic acid

Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated, i.e. contiguous. CLA was identified as a component of milk and dairy products over 20 years ago. It is formed as an intermediate in the course of the conversion of linoleic acid to oleic acid in the rumen. The predominant naturally occurring isomer is the cis-9, trans-11 modification. Treatment of linoleic acid-rich oils such as safflower oil, soybean oil, or maize oil with base and heat will result in the formation of CLA. Two isomers predominate in the synthetic preparation, c9,t11 and t10,c12. CLA has been shown to inhibit chemically-induced skin, stomach, mammary or colon tumours in mice and rats. The inhibition of mammary tumours in rats is effective regardless of type of carcinogen or type or amount of dietary fat. CLA has also been shown to inhibit cholesterol-induced atherosclerosis in rabbits. When young animals (mice, pigs) are placed on CLA-containing diets after weaning they accumulate more body protein and less fat. Since CLA is derived from the milk of ruminant animals and is found primarily in their meat and in products derived from their milk there is a concerted world-wide effort to increase CLA content of milk by dietary means. Its effect on growth (less fat, more protein) is also a subject of active research. The mechanisms underlying the effects of CLA are still moot.

Impact of Red Palm Oil on Human Nutrition and Health

The oil that is first obtained in harvesting the fruit of the oil palm is red because it contains carotenes, tocopherols, and tocotrienols. in the past, this fraction was separated from the palm olein and used separately. However, the presence of the palm oil tocopherol-rich fraction (TRF) is what makes red palm oil unique. Red palm oil has been shown to increase retinol levels in populations with marginal vitamin A deficiency. Red palm oil also reduces the severity of cholesterol-induced atherosclerosis in rabbits (compared with palm olein). There has been considerably more work done with TRF than with red palm oil per se. Some authors find it to be hypocholesterolaemic, whereas others do not. Many, but not all, studies show TRF to have antitumorigenic properties as well. More data concerning the health effects of red palm oil are needed.

Marked inhibition of hepatic cytochrome P450 activity in cholesterol-induced atherosclerosis in rabbits

The objective of the present study was to investigate the expression of major xenobiotic-metabolising cytochrome P450 proteins, and of other enzyme systems, in hepatic and extrahepatic tissues of rabbits rendered atherosclerotic by the dietary administration of 1% cholesterol diets for 8 weeks. Individual cytochrome P450 proteins were monitored using diagnostic substrates and immunologically in Western blot analysis. The activity of all hepatic isoforms studied was depressed in the atherosclerotic animals; when, however, apoprotein levels were determined immunologically, no major differences were evident between the control and the atherosclerotic rabbits. In vitro studies indicated that neither cholesterol nor palm oil inhibited cytochrome P450 activity. The effects of cholesterol treatment leading to atherosclerosis on kidney, heart and lung cytochrome P450 activities were isoform- and tissue-specific; no change was evident in the heart activities, but in the lung and kidney cytochrome P450 activities were clearly modulated by the treatment with cholesterol. Apoprotein levels did not always parallel the changes in activities. Western blot analysis of aortic cytochromes P450 revealed that administration of cholesterol-rich diets enhanced CYP2B and CYP3A apoprotein levels. Cholesterol feeding to rabbits gave rise to a marked decrease in hepatic glutathione S-transferase activity but did not influence glutathione reductase or total glutathione levels. The same treatment had no effect on catalase, glutathione peroxidase and superoxide dismutase. It is concluded that treatment of rabbits with cholesterol-rich diets leading to atherosclerosis gives rise to profound changes in the expression of cytochrome P450 proteins in the liver and other tissues; possible mechanisms are discussed.

Effect of Vitamin E and Probucol on Dietary Cholesterol-Induced Atherosclerosis in Rabbits

The preventive effect of vitamin E and Probucol against atherosclerosis in rabbits were compared. Atherosclerosis was induced by a 2% cholesterol-containing vitamin E-poor diet (5–10 ppm). Six groups of five rabbits each were studied. Group I (control) was fed on a vitamin E-poor diet. The other groups had the following supplements: group II, 50 mg/kg vitamin E i.m.; group III, 2% cholesterol; group IV, 2% cholesterol plus 50 mg/kg vitamin E i.m., group V, 2% cholesterol plus 1% Probucol; group VI, 2% cholesterol + 1% Probucol plus 50 mg/kg vitamin E i.m. After 4 weeks, aortas were removed and analyzed by light and scanning electron microscopy for atherosclerotic lesions. Samples of the media were analyzed for protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by microscopic examination, their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol-induced atherosclerotic lesions and the induction of protein kinase C activity. Probucol was not effective in preventing either cholesterol-induced atherosclerotic lesions or the induction of protein kinase C activity. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as Probucol, and therefore, may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells ex vivo suggest an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis.

Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages.

The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein (LDL) oxidation was examined in 20 treated hypertensive subjects. The randomized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil. Fish oil significantly (-24%, P < 0.01) reduced plasma triglyceride, and increased LDL-cholesterol (+6%, P < 0.01 compared to corn oil). LDL particles were larger (P < 0.01) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride (P < 0.001) both before and after fish oil supplementation, and positively correlated with high density lipoprotein cholesterol (P < 0.01). Fish oil reduced lag time before onset of copper-induced LDL oxidation (-25%, P < 0.001) and significantly increased production of thiobarbituric acid-reactive substances (TBARS) during oxidation, compared with corn oil. Corn oil had no significant effect on lag time and oxidation rate. Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL. Corn oil was without effect. Additionally, macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly (P < 0.001) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids. We conclude that from the standpoint of atherosclerosis, fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable.

Chromium and Cholesterol-Induced Atherosclerosis in Rabbits

Thirty-three rabbits on a cholesterol-enriched diet were randomized into 6 groups and treated with daily injections of either water, 20 micrograms of potassium chromate or 1, 5, 10 or 20 micrograms of chromium chloride, respectively, for 135 days with a 2- to 10-fold increase in serum chromium. There was a marked reduction in the percentage of aortic intimal surface covered by plaque, in aortic weight and cholesterol content in the treated animals. Rabbits treated with 20 micrograms of chromium chloride showed a better response than those treated with either 10 or 20 micrograms of potassium chromate.

Clinical and Experimental Approaches to the Prevention of Atherosclerosis by Immunological Regulations

To evaluate the involvement of the complement system in atherogenesis, we investigated the effect of camostat mesilate (CM), C1r, and C1 esterase inhibitor on cholesterol-induced atherosclerosis in rabbits. We also examined the effect of sodium dextran sulfate (DS, molecular weight: 7000), which is reported to be effective in preventing arteriosclerotic diseases and in inhibiting cholesterol-induced atherosclerosis in experimental animals, on complement activation in vitro and in vivo. The administration of CM reduced the formation of atherosclerotic lesions in cholesterol-fed rabbits. DS inhibited complement pathway in vitro, and the administration of DS reduced the C3a level in subjects. These results suggest that complement activation may possibly be involved in the atherosclerotic process.

The Ayurvedic medicines Haritaki, Amla and Bahira reduce cholesterol-induced atherosclerosis in rabbits

Four groups of 25 rabbits each, were studied to determine the effect of Haritaki ( Terminalia chebula), Amla ( Emblica officinalis) and Bahira ( Terminalia belerica) on cholesterol-induced hypercholesterolaemia and atherosclerosis. The control group was fed with cholesterol alone; the Haritaki group received Haritaki and cholesterol; the Bahira group received Bahira and cholesterol; and the Amla group received Amla and cholesterol for 16 weeks. Cholesterolaemia was significantly less ( P < 0.001) in the Haritaki group (166 mg/dl), the Bahira group (240 mg/dl) and the Amla group (205 mg/dl) than in the control group (630 mg/dl). The Haritaki group had significantly less cholesterolaemia ( P < 0.001) as compared to the Bahira and Amla groups. Aortic sudanophilia was significantly less ( P < 0.001) in the Haritaki group (6%), the Bahira group (16%), and the Amla group (12%) than in the control group (38%). The cholesterol contents of the liver and aorta, respectively, were significantly less in the Haritaki group (46 mg/100 g, 28 mg/100 g), the Bahira group (78 mg/100 g, 72 mg/100 g) and the Amla group (46 mg/100 g, 42 mg/100 g), than in the control group (604 mg/100 g, 116 mg/100 g). Among the drug-fed groups, the Haritaki group had significantly lower degrees of sudanophilia and cholesterol content of aorta and liver ( P < 0.001) as compared to the Bahira and Amla groups. Although all three drugs reduced serum cholesterol, aortic sudanophilia and cholesterol contents of liver and aorta, their effects were in ascending order of magnitude. The drugs did not influence serum triglyceride levels, euglobulin clot lysis time or platelet adhesiveness. As they did not cause increased excretion of cholesterol, their action might be mediated through enzymic degradation of cholesterol in the liver or elsewhere. It is suggested that the active principles of these drugs should be identified and the hypocholesterolaemic effects evaluated in man.

The beneficial influence of nifedipine on the regression of the cholesterol-induced atherosclerosis in rabbits.

Nifedipine has been implicated as an inhibitor of dietary induced atherosclerosis in rabbits. This study was designed to examine the effect of nifedipine on the regression of atherosclerotic lesions in this animal model. NZ-rabbits were fed a cholesterol-enriched diet (1.5%) for 4.8 months. A control group A was killed and the aorta removed for planimetry of the vessel wall lesions. The remaining animals were divided into two groups, group P receiving a placebo solution and group N a nifedipine solution (2 X 20 mg/day). They were maintained on a standard chow for a further 4.5 months. In the nifedipine-treated group N, sudanophilia of the aorta was reduced by more than 20% as compared to the cholesterol-fed control group A and was 50% lower than in the placebo-treated group. Total cholesterol of the aortic tissue was lowest in group N. No significant differences in plasma cholesterol, triglycerides or the platelet half-life time were observed between the placebo- and the nifedipine-treated group. These data indicate that nifedipine can stimulate regression of pre-existing atherosclerotic lesions in rabbits.

Surprising effects of the sequential administration of pentoxifylline and low dose acetylsalicylic acid on thrombus formation's

The effect of the combined oral administration of pentoxifyl-line (pof) and low dose acetylsalicylic acid (ASA) was evaluated with the help of the laser-induced thrombosis in rat mesenteric arterioles. Laser-induced thrombosis is inhibited in a dose-dependent way by both drugs. The administration of ASA, either simulataneously with or 1 hour prior to pof, does not show any effects in the laser model. On the contrary, the administration of pof followed 1 h later by ASA not only exhibited a significant effect but also produced a supraadditive inhibition of the laser-induced thrombus formation. Specific investigations concerning the time interval between the administration of both drugs determined that a significant effect can be achieved only after an interval of 30 to 90 minutes (principle of HWA 5112). The striking results could also be shown in diseased animals after sequential chronic administration of pof 1 h prior to ASA. HWA 5112 exhibits significant effects on laser-induced thrombus formation in the following chronic animal models: 1. adjuvant arthritic rats, 10→1 mg/kg for 21 days; 2. spontaneously hypertensive stroke-prone rats, 10→1 mg/kg three times within 24 h; 3. cholesterol-induced atherosclerosis in rabbits, 10→1 mg/kg for 14 days. The reported data clearly demonstrate that the sequential drug administration of first pentoxifylline followed 30 to 90 min later by ASA exhibits a supraadditive antithrombotic effect.

Atherogenesis preventive action of trifluoperazine

This preliminary note describes the preventive action of trifluoperazine against cholesterol-induced atherosclerosis in rabbits. Although this drug had no significant effect on the elevated levels of serum lipids induced by the atherogenic diet, it completely inhibited the initiation of atherosclerotic lesions in rabbits fed atherogenic diets. Based on these findings, we propose that calmodulin and protein kinase “C” may play a key role in the development of the atherosclerotic process.

Fish oil feeding results in an enhancement of cholesterol-induced atherosclerosis in rabbits

We investigated the influence of fish oil on cholesterol induced atherosclerosis in rabbits. Group I, a control group was fed a cholesterol-free diet, group II was fed a diet supplemented with 1.5% cholesterol, group III received in addition to cholesterol supplementation a purified fish oil concentrate (Maxepa ® 2 ml/d). The animals received these diets for 5 months (100 g/d). Aortic atherosclerosis as measured by planimetry of sudanophilic lesions was significantly higher (+59%) in group III as compared with group II, even though serum cholesterol levels were comparable. No differences were found in platelet half-life times between groups II and III, but these values were significantly lower than the half-life of platelets in the control group I. Total serum peroxide levels, expressed as malondialdehyde equivalents were significantly elevated in the fish oil-treated group. This may be due to malondialdehyde modification of the lipoproteins and may be responsible for the enhanced development of atherosclerosis in these animals.

Suppression of atherosclerosis in cholesterolemic rabbits by dimethyl sulfoxide.

Abstract : The results of this study indicate that DMSO retards the development of dietary cholesterol-induced atherosclerosis in rabbits and suppresses the accumulation of cholesterol in tissues despite severe hypercholesterolemia. While the mechanism of action of DMSO in suppressing atheosclerosis is not known, our in vitro studies suggest that one of its antiatherogenic effects is related to its capacity to reduce the binding, uptake, and degradation of plasma LDL by tissues and cells.

Metformin action on lipid metabolism in lesions of experimental aortic atherosclerosis of rabbits

The aim of the present study was to investigate whether metformin was capable of altering aortic lipid metabolism during the progression and regression of cholesterol-induced atherosclerosis in rabbits. Three hours after intravenous injection of a 200-μCi tracer dose of [2- 14C]acetate, metformin (120 mg/kg per os) strongly diminished the radioactivity in all lipid fractions of the aorta of the normal rabbit. The incorporation of acetate into lipids was greater in the fatty streaks of rabbits fed cholesterol for 2 months than in normal aorta, independent of the plasma radioactivity level. There was increased acetate incorporation into all major lipid groups in the fatty streak, with the greatest relative increase in the cholesteryl ester fraction. No change was observed in the acetate incorporation into lipids in atheromatous deposits after pretreatment of cholesterol-fed rabbits for 8 days with metformin. Concomitant treatment for 2 months with metformin in rabbits fed a cholesterol-enriched diet strongly reduced the radioactivity of total aortic lipids 3 h after intravenous injection of labelled acetate. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free cholesterol, free fatty acids, triglycerides and especially esterified cholesterol and phospholipids). In rabbits fed a cholesterol-enriched diet for a period of two months, followed by a normal diet during 12 months, long-term treatment with metformin significantly reduced total lipid radioactivity in the aorta, 3 h after intravenous injection of the 200-μCi tracer dose of [2- 14C]acetate. The incorporation of labelled precursor was markedly reduced in the various lipid fractions. These properties, added to others previously described, can to a large extent explain the protective effect of metformin on experimental atherosclerosis.

The effect of chromium on cholesterol-induced atherosclerosis in rabbits

Rabbits fed on a 1% cholesterol diet for 30 days were injected daily with potassium chromate for a further 60 days. A 50% reduction in aortic intimal plaque area and in aortic total cholesterol content was observed. Control rabbits treated with chromium showed a significant increase in the chromium concentration of their aortas, liver and kidneys but not of the myocardium. Cholesterol-fed rabbits treated with chromium showed a significant increase in chromium concentrations in the liver and kidneys only. Serum cholesterol levels were consistently lower in the chromium-treated animals, although the differences did not reach significant levels.

Influence of milk, yoghurt and calcium on cholesterol-induced atherosclerosis in rabbits

Five groups of rabbits were studied to determine the effect of milk, yoghurt and calcium on cholesterol-induced hypercholesterolaemia and atherosclerosis. The experiment lasted for only 16 weeks. Yoghurt, calcium and milk reduced serum cholesterol levels in rabbits fed on the cholesterol diet. There was no significant difference in the cholesterol levels in the yoghurt and calcium groups. Yoghurt caused a greater extent of hypocholesterolaemia than milk (P < 0.001). Aortic sudanophilia was maximal in the cholesterol-fed group, while there was no sudanophilia in the yoghurt-fed group. The milk and calcium groups showed an intermediate degree of sudanophilia. Aortic sudanophilia correlated with the serum cholesterol level (r = +0.65). It is suggested that calcium is an active factor in yoghurt, but that other hypocholesterolaemic agents may also be present.