Hyperlipidemia In Rabbits Research Articles

Investigation of phytotherapeutic potential of herbal mixtures and their effects on salbutamol induced cardiotoxicity and hyperlipidemia in rabbits

BackgroundCardiovascular diseases (CVDs) are the major cause of deaths all over the world. The high level of blood cholesterol and oxidative stress are major risk factors for heart diseases. The phytotherapeutics have attracted attention as potential agents for preventing and treating oxidative stress associated diseases. The objective of present study was to evaluate the synergetic cardio-protective and antilipidemic potential of medicinal plants viz. Coriandrum sativum, Piper nigrum and Cactus grandiflorus. Cardio-protective and anti-lipidemic potential of herbal mixture was evaluated against salbutamol induced cardiotoxicity in rabbits. For this purpose, rabbits were divided into six groups as normal control, salbutamol control, curative and standard drug curative.ResultsSalbutamol significantly (p < 0.05) increased the level of serum cardiac biomarkers (ALT, CK-MB, AST and LDH) and lipids (LDL, triglycerides, cholesterol) in rabbits. The prior and post administration of herbal mixture significantly (p < 0.05) lowered the elevated level of serum cardiac biomarkers and lipids equal to normal control. Gross pathological examination revealed that heart of salbutamol control animals became hardened, congested and were enlarged than preventive and curative groups. The phytotherapeutic analysis of medicinal plants revealed the presence of phenols, tannins, alkaloids and steroids.ConclusionThe results showed that this herbal mixture has strong cardio-protective and anti-lipidemic potential.

Effect of Momoridica chorantia (Bitter Melon) Fruit extract on Homocysteine Levels and Lipid Profile in experimentally induced Hyperlipidemia in Rabbits

Effect of Momoridica chorantia (Bitter Melon) Fruit extract on Homocysteine Levels and Lipid Profile in experimentally induced Hyperlipidemia in Rabbits

Antioxidant and antihyperlipidemic activity of Costus speciosus against atherogenic diet-induced hyperlipidemia in rabbits

ObjectiveAn extract of Costus speciosus (CSE), a herb widely used in folk medicine, was evaluated for its antioxidant, antihyperlipidemic and ameliorating effects on histopathological changes in atherogenic rabbits. MethodsTwenty-four male rabbits (Oryctolagus cuniculus) were divided into 4 groups. Three groups were fed a diet containing 3% saturated fat and 1.3% cholesterol for 40 d. One of these was sacrificed on the 40th day and was called the pathogenic (P) group; the other two groups received treatment for another 30 d as follows: one received 0.8 g/(kg·d) of CSE and the other was given 0.01 g/(kg·d) of simvastatin. The normal group was sacrificed on the 70th day and used as a control. ResultsCSE showed radical-scavenging ability. Administration of CSE for a 30-day period resulted in a significant decrease in total cholesterol, triacylglycerol, low-density lipoprotein and aspartate aminotransferase compared to the P group, while levels of hemoglobin, packed corpuscular volume and red blood cells were elevated. With respect to studies performed on the heart, a decrease in malondialdehyde and an increase in reduced glutathione were noted. Total protein increased in the liver, heart and aorta after treatment with CSE and also a marked improvement in histopathological parameters was demonstrated. ConclusionThe present findings indicate that the C. speciosus rhizome possesses antiatherogenic and antioxidant properties which may provide protective effects against oxidative stress in atherosclerotic rabbits.

Effect of Haematogenous oxidation therapy with Ultraviolet-C irridation in an alloxan-induced diabetes and a Poloxamer 407-induced Hyperlipidemia in rabbits

Effect of Haematogenous oxidation therapy with Ultraviolet-C irridation in an alloxan-induced diabetes and a Poloxamer 407-induced Hyperlipidemia in rabbits

Evaluation of Antihyperlipidaemic Activity of Methanolic Extract of Cuminum cyminum L. Seeds in Diet Induced Hyperlipidaemic Rabbits

Objective: To evaluate antihyperlipidaemic activity of methanolic extract of seeds of Cuminum cyminum L. in hyperlipidaemia in rabbits.&#x0D; Methods: This study was conducted in Pharmacology Department of University of Karachi; the duration of study was 30 days. Healthy rabbits were taken and hyperlipidaemia was induced by giving high cholesterol diet for four weeks. All animals were divided into three groups, with each group having ten rabbits (n=10).The methanolic extract of seeds of Cuminum cminum L. was dissolved in an organic solvent DMSO (Dimethyl-sulphoxide). One group was control-receiving DMSO, while second group received methanolic extract of Cuminum cyminum L. (MECC) 500mg/kg and third group re- ceived Atorvastatin 2mg/kg.Blood samples were taken at 0, 15th and 30th day of dosing and sent for the tests to Punjwani Centre for Molecular medicine &amp; Drug research (PCMD) Diagnostic Laboratory.&#x0D; Results: The group that was given methanolic extract of Cuminum Cyminum L. showed decrease in High Density Lipoprotein (HDL) - cholesterol ratio (7.62 ± 4.01 to 4.45 ± 3.23) (p&lt;0.05), cholesterol (208.54 ± 5.71 to 130.26 ± 5.72) (p&lt;0.01), triglyceride (158.75 ± 5.23 to 136.14 ± 8.72) (p&lt;0.001) and Low Density Lipoprotein (LDL) (168.17 ± 5.43 to 135.42±11.39) (p&lt;0.001) and the group that was given Atorvastatin showed HDL-cholesterolratio(7.33 ± 3.27 to 3.12 ± 2.19) (p&lt;0.01), cholesterol (208.11 ± 6.72 to 98.75 ± 3.77) (p&lt;0.001), triglyceride (157.21 ± 6.72 to 141.25 ± 6.84) (p&lt;0.01) and Low Density Lipoprotein (LDL) (167.25 ± 4.32 to 127.67 ± 10.96) (p&lt;0.001) towards its normal levels from day 0 to 30th day of dosing on comparison to control, whereas triglycerides were significantly de- creased by extract than atorvastatin.&#x0D; Conclusion: The result of this study showed methanolic extract of Cuminum cyminum L. possesses antihyperlipidaemic activity.

Proteomic analysis and comparison of intra- and extracranial cerebral atherosclerosis responses to hyperlipidemia in rabbits

The present study aimed to investigate protein expression levels of intra- and extracranial atherosclerosis in rabbits following administration of a high-fat diet. Rabbits were randomly divided into control (group A; n=9) and high-fat diet (group B; n=9) groups. At week 12, tissues were sectioned from the common carotid artery (CCA) and middle cerebral artery (MCA). Pathological analysis was performed. Differential protein expression levels were examined by 2-D gel electrophoresis (2-DE) and mass spectrometry (MS) analysis and validated by western blotting. Serum lipid levels, the intima-media thickness (IMT) and degree of atherosclerosis of the CCA and MCA were increased at week 12 in the high-fat diet group compared with rabbits that received a normal diet. 2-DE and MS analysis of the protein extracted from CCA and MCA detected >439 different proteins; the expression of 25 proteins was altered, and 8 proteins [albumin A chain, tropomyosin α-1 chain (TPM1), heat shock protein 70 (HSP70), α-smooth muscle actin, β-galactose binding agglutinin, TPM4 isoform 2, cell keratin 9, single octylic acid glyceride β-2) demonstrated significant alterations in expression levels. Due to limited antibody sources, only three differentially expressed proteins (TPM1, HSP70 and α-smooth muscle actin) were examined by western blotting. The results of our previous study demonstrated that hyperlipidemia affected the IMT of intracranial and extracranial cerebral arteries. In the present study, protein expression levels of TPM1 and α-smooth muscle actin from extracranial cerebral arteries were significantly increased compared with intracranial cerebral arteries; however, protein expression levels of HSP70 from intracranial cerebral arteries was increased compared with extracranial cerebral arteries. The differences may be closely associated with cell proliferation and metastasis, and oxidoreduction, in intra- and extracranial cerebral atherosclerosis. HSP70 may have protective properties against atherosclerosis via underlying anti-inflammatory mechanisms, furthermore, differential protein expression levels (TPM1, HSP70 and α-smooth muscle actin) between intra- and extracranial cerebral arteries may facilitate the identification of novel biological markers for the diagnosis and treatment of cerebral arteriosclerosis.

Effect of nifedipine and glibenclamide addition in a model of high fat diet- induced hypertension and hyperlipidemia in rabbits receiving donepezil.

Effect of nifedipine and glibenclamide addition in a model of high fat diet- induced hypertension and hyperlipidemia in rabbits receiving donepezil.

A STUDY OF THE HYPOLIPIDEMIC AND ANTIOXIDANT ACTIVITIES OF WHOLE PLANT EXTRACTS OF IPOMOEA AQUATICA FORK IN EXPERIMENTALLY INDUCED HYPERLIPIDEMIA IN RABBITS

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of the study has been to investigate the possible hypolipidemic and antioxidant properties of the whole plant extract of &lt;em&gt;Ipomoea aquatica&lt;/em&gt; in experimentally induced hyperlipidemia in rabbits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Ethanolic extract of &lt;em&gt;I. aquatica&lt;/em&gt; whole plant (EEIAWP) was prepared by percolation method. The extract was evaluated for hypolipidemic and antioxidant activities using 400 mg/kg body weight per day in a high fat diet induced hyperlipidemia in rabbits. The results were analyzed using one-way analysis of variance (ANOVA) followed by Bonferroni’s multiple comparison tests and compared to the normal control, experimental control and the standard drug (atorvastatin 2.1 mg/kg body weight per day) groups. The results were expressed as mean±standard error of mean (SEM). Values with &lt;em&gt;p&lt;/em&gt;&amp;lt;0.05 were considered significant.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Oral administration of EEIAWP in the test group showed a significant reduction in the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and a significant increase in the high-density lipoprotein cholesterol (HDL-C) when compared to the experimental control group. There were also significantly elevated catalase and superoxide dismutase (SOD) activities and significantly lower malondialdehyde (MDA) levels in the test group compared to the experimental group. Similar results were also found in the standard drug group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The results of our experiment demonstrated that EEIAWP possesses significant antihyperlipidemic and antioxidant activities and hence could be a potential source of medication as an adjuvant to the existing therapy for treatment of dyslipidemia.&lt;/p&gt;

Effect of Fenugreek Seeds Powder (Trigonella foenum-graecum L.) on Experimental Induced Hyperlipidemia in Rabbits

ABSTRACTIn the present experimental study, the effect of Trigonella foenum-graecum L. (TFG) seeds powder on experimentally induced hyperlipidemia in rabbits was investigated. Twenty albino rabbits were randomly, equally divided into two groups and fed pure cholesterol (0.5g/kg body weight/day) for the period of eight weeks to develop hyperlipidemia. Group-I (control) and Group-II received a normal diet with 2 mL normal saline and 2 mL aqueous emulsified TFG seeds powder (500 mg/kg body weight/day) for four weeks, respectively. Lipid profile and weight were measured at baseline after eight weeks and at the end of the study (12 weeks). Atherogenic indices were calculated by Friedewalds formula. Statistical analysis was performed using IBM: SPSS version 20, and student t test was used to compare variables between groups. After eight weeks of study period, cholesterol feeding was discontinued and hyperlipidemic value was compared with the initial baseline data. Significant increase in body weight and lipid profile variables were observed in the two groups, while there was a significant decrease in high-density lipoprotein cholesterol (HDL-C). After the end of the study (12 weeks), the aqueous emulsified fenugreek (TFG) seeds powder reduced significantly the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and the atheriogenic index (P < 0.001), with significant increase in the HDL-C (P < 0.001) in experimentally hyperlipidemic rabbits (P < 0.001) as compared to control group, whereas no significant differences were observed in the triglyceride very low-density lipoprotein cholesterol (VLDL-C) and body weight (P > 0.05) of both groups. It was concluded that fenugreek seeds powder had a significant hypolipidemic effect in experimentally-induced hyperlipidemic rabbits.

Therapeutic potential of ethanolic extract of Solanum nigrum for lipofundin-induced hyperlipidemia in Rabbits

Attenuation of hyperlipidemia with extract of medicinally important plant and reversal of lipid disorders is clinically very important. The aim of present study was to identify the therapeutic potential of Solanum nigrum ethanolic extract in lowering the cholesterol level in lipofundin treated hyperlipidimic rabbits in vivo. 20% lipofundin was used to induce hyperlipidmia in rabbits @ 2 ml/kg body weight through slow intravenous administration in the marginal ear vein for 7 days. For next 2 weeks the control group was placed at standard diet, whereas the test group was given the ethanolic crude extract of Solanum nigrum at the dose of 300 mg/kg body weight. On the completion of treatment blood samples were collected from both control and test groups and were analyzed for the lipid profile values. It was observed in the test group after treatment with ethanolic extract of S. nigrum, the raised level of serum total cholesterol, triglyceride, highdensity lipoprotein, low-density lipoprotein were decreased towards normal values. Thus the present study demonstrated that S. nigrum possessed significant anti-hyper lipidimic activity in lipofundin induced hyperlipidimic rabbits.

A Comparative Study of Lipid-Lowering Effects of Guggul and Atorvastatin Monotherapy in Comparison to Their Combination in High Cholesterol Diet-Induced Hyperlipidemia in Rabbits

ABSTRACTBackground: Hypolipidemic activity of gugulipid has been widely described in traditional literature. Objective: This study was done to evaluate hypolipidemic activity of guggul and atorvaststin monotherapy in comparison to their combination in rabbits. Materials and Methods: Male New Zealand White rabbits (body weight 1.3–1.8 kg and age 8–10 weeks) were made hyperlipidemic by feeding cholesterol (0.5 g/kg) for three weeks and randomly divided into a control and three treatment groups receiving: atorvastatin (3.7 mg/kg), guggul (3.5 mg/kg) and their combination (same dose) for the next three weeks. Body weight measurements, estimation of serum lipid profile were done at the beginning, after three and six weeks, respectively. Histopathological examination of liver, heart and aorta was done after six weeks. Statistical analysis was done with SPSS version 16.0 using one-way and repeated measures analysis of variance (ANOVA) followed by post-hoc multiple comparison test with two tailed P value < 0.05 as significant. Results: All treated groups had significant reduction in cholesterol, triglyceride, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) in comparison to pre-treatment values and control group, and had significant increase in high-density lipoprotein (HDL) in comparison to pre-treatment values. Conclusion: Combination of atorvastatin and guggul was comparable to their monotherapies in improving lipid profile.

Urinary Trypsin Inhibitor Reduced Inflammation Response Induced by Hyperlipidemia.

Atherosclerosis is recognized as a chronic inflammatory disease. The aim of this study was to examine the role of urinary trypsin inhibitor (UTI) in inflammation response induced by hyperlipidemia in rabbits. Thirty rabbits after injury of the right iliac artery endothelium were randomly divided into 3 groups: control group, model group, and UTI group. Iliac arteries were isolated and histology was performed on arterial regions that were injured by balloon after 8 weeks. Neointimal thickness (NT) and neointimal to media radio (N/M) were measured. Blood lipids, interleukin 6, and tumor necrosis factor-α were evaluated. Macrophages were evaluated by immunohistochemical analysis. MicroRNA-181b (miR-181b) was measured by reverse transcriptase-polymerase chain reaction. Urinary trypsin inhibitor therapy decreased serum inflammatory factor levels without significant changes in blood lipids. Compared with model group, UTI reduced macrophage infiltration of iliac artery (13.91 ± 2.03% vs 24.21 ± 8.94%, P < .01). Hyperlipidemia reduced the expression of miR-181b and increased NT and N/M ratio. Systemic administration of UTI rescued miR-181b expression and inhibited neointimal formation. Urinary trypsin inhibitor could reduce neointimal hyperplasia by inhibiting inflammatory response induced by hyperlipidemia and may become a potential antiatherosclerosis supplement.

Effect ofMyristica fragranson Lipid Profile in Experimentally Induced Hyperlipidemia in Rabbits

Aim: The aim of the present study was to evaluate the effect of aqueous extract from fruit of Myristica fragrans (MF) on lipid profile and lipid peroxidation in rabbits. Materials and Methods: The experiment was conducted on four groups of rabbits with six animals in each group. Group I received standard pellet diet, Group II aqueous extract of MF only, Group III received high fat diet (HFD), Group IV received HFD supplemented with MF. After 14 weeks of the experimental period, animals were fasted overnight and blood was taken for estimation of total cholesterol (TC), triglyceride (TG), high density cholesterol (HDL-C) and malondialdehyde (MDA). Results: MF significantly lowered the TC, TG and MDA levels in Group II rabbits as compared to Group I. In rabbits fed on HFD, MDA and TC were significantly increased. However, in rabbits of Group IV MF supplementation led to increase in levels of HDL-C but plasma MDA and TC were reduced as compared to Group III. Conclusion: This study suggests that some active ingredient in MF may have an antioxidant action which can protect against cardiovascular diseases by altering lipid profile.

The effects of eicosapentaenoic acid on the endothelium of the carotid artery of rabbits on a high-cholesterol diet.

The preventive and therapeutic effects of eicosapentaenoic acid (EPA) on diet-induced hyperlipidemia in rabbits have been investigated. Eighteen New Zealand rabbits were randomly divided into three groups of 6 subjects each; experimental group-I (EG-I) was administered a cholesterol rich diet, experimental group-II (EG-II) was treated with EPA (300 mg/kg/d) following a cholesterol-rich diet and the control group (CG) had a standard diet. Blood samples were collected at day 0 and at the 4th and 12th weeks of EG-II to obtain serum levels of total cholesterol (TC), high density lipid-cholesterol (HDL-C), low density lipid-cholesterol (LDL-C) and triglyceride (TG). From each group tissue samples were collected from the carotid artery for immunohistochemistry and electron microscopy. Our results showed that EPA could significantly lower (p<0.001) serum TC, LDL-C, HDL-C and TG levels with a reduction of 35%; 55%; 44% and 51%, respectively. Scanning and transmission electron microscopy results revealed that endothelial damage was more prominent in EG-I when compared to EG-II. The ruptured endothelial lining and damaged cellular surface was increased in EG-I when compared to EG-II. Ultrastructural observations showed that after EPA treatment, the degeneration and cellular surface damage on the endothelium were also decreased. These biochemical and ultrastructural results suggest that EPA is a potential drug which significantly lowers the serum lipid profile and partially repairs endothelial dysfunction due to hyperlipidemia.

Antioxidant effect of Triticum aestivium (wheat grass) in high-fat diet-induced oxidative stress in rabbits

Wheat grass is used as a general health tonic and is reported to be effective against several medical disorders, although detailed literature is not available. Besides drug therapy, a number of medicinal plants are effective in treating hyperlipidemia. This study examined the effects of wheat grass on high-fat diet-induced hyperlipidemia in rabbits. Thirty rabbits were divided into 3 groups of 10 rabbits each, group I receiving a control diet, group II a high-fat diet and group III a high-fat diet together with wheat grass over a period of 10 weeks. Fasting serum samples from the animals were analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), reduced glutathione (GSH) and vitamin C, and the results were compared. The high-fat diet resulted in hyperlipidemia and an increase in oxidative stress, indicated by a significant rise in MDA levels, whereas antioxidant levels of GSH and vitamin C were significantly reduced. Wheat grass supplementation with a high-fat diet resulted in improved lipid levels (decreased total cholesterol and increased HDL-C) together with significantly reduced MDA levels and increased GSH and vitamin C levels. These results indicate the beneficial role of wheat grass in ameliorating hyperlipidemia and the associated oxidative stress.

The Effect of Garlic on Cholesterol Induced Hyperlipidaemia in Rabbits

An experimental biochemical study was made on rabbits to demonstrate the possible role of aqueous extract of garlic as an antilipidaemic agent in the prevention of hyperlipidaemia. Untreated rabbits on atherogenic diet showed worse lipidaemic status than the normal control ones, as evident in higher serum cholesterol, triglycerides (TG), low-density lipoprotein (LDL) and lower high-density lipoprotein (HDL) level. On the otherhand the rabbits on atherogenic diet treated with aqueous extract of garlic showed significantly better lipidaemic status. It is suggested that aqueous extract of garlic is an important determinant of serum lipid level, which is an antilipidaemic agent against the pathogenesis of atherosclerosis. Ibrahim Med. Coll. J. 2007; 1(1): 16-20 Key words: Garlic; Cholesterol; hyperlipidaemia doi: 10.3329/imcj.v1i1.2890

Evaluation of rat and rabbit sera lipoproteins in experimentally induced hyperlipidemia by analytical ultracentrifugation

Animals of various species are widely used as models with which to study atherosclerosis and the lipoprotein metabolism. The objective of this study was to investigate the lipoprotein profiles in Wistar rats and New Zealand white rabbits with experimentally induced hyperlipidemia by means of ultracentrifugation. The Schlieren curves were utilized to compare suckling and adult rat sera to determine whether aging causes alterations in lipoprotein profiles. A striking feature of the data is the high concentration of low-density lipoproteins (LDL), (>5.2 mmol/l cholesterol) in the 2-week old rat serum pool which was greatly decreased in the 3-weeks rat serum pool (<1.3 mmol/l cholesterol). Additional experiments were performed to permit a direct comparison of the amounts of lipoprotein present in rat sera in experimental hyperlipidemia post-Triton WR 1339 administration. Rapid changes in concentrations in very low-density lipoproteins (VLDL), LDL and high-density lipoproteins (HDL) were observed after Triton injection. The administration of Triton WR 1339 to fasted rats resulted in an elevation of serum cholesterol levels. Triton physically alters VLDL, rendering them refractive to the action of lipolytic enzymes in the blood and tissues, preventing or delaying their removal from the blood. Whereas the VLDL concentration was increased markedly, those of LDL and HDL were decreased at 20 h after Triton treatment. Rabbits were fed a diet containing 2% cholesterol for 60 days to develop hyperlipidemia and atheromatous aortic plaques. A combination of preparative and analytical ultracentrifugation was used to investigate of LDL aliquots, to prepare radioactive-labeled lipoproteins and to study induced hyperlipidemia in rabbits. Analytical ultracentrifugation was applied to investigate the LDL flotation peaks before and after cholesterol feeding of rabbits. Modified forms of LDL were detected in the plasma of rabbits with experimentally induced atherosclerosis. ApoB-containing particles, migrating as LDL, intermediate density lipoproteins and VLDL were the most abundant lipoproteins. Gamma camera in vivo scintigraphy on rabbits with radiolabeled lipoproteins revealed visible signals corresponding to atherosclerotic plaques of the aorta and carotid arteries.

Effects of Anxin Granules on blood lipid and ultrastructure of aorta in rabbits with dyslipidemia

To study the effects of Anxin Granules on dyslipidemia in rabbits caused by high fat plus high cholesterol diet. Thirty-two healthy New Zealand male white rabbits were randomly divided into 4 groups: normal control group, untreated group, Zhibituo Tablet-treated group and Anxin Granule-treated group. Rabbits in the normal control group were fed with regular chow, while rabbits in the other three groups were fed with high fat plus high cholesterol diet. Zhibituo Tablets and Anxin Granules were administered to the rabbits in Zhibituo Tablet-treated group and Anxin Granule-treated group at a daily oral dose respectively. At the end of the 10th week, the levels of serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A(1) (ApoA1) and apolipoprotein B (ApoB) were tested in each group, and the ultrastructures of the aorta were also observed by an electron microscope. Anxin Granules could reduce the levels of TC, TG, LDL-C and ApoB. The results observed by electron microscope showed that, as compared with the untreated group and the Zhibituo Tablet-treated group, the atherosclerosis of aorta in the Anxin Granule-treated group was lighter. And it was found that there were few lipid droplet vacuoles in cytoplasm of the endothelial cells, and various cell organs and elastic membrane were existed, but no lipid droplet vacuoles in cytoplasm of the medial smooth muscle cells. Anxin Granules can regulate the metabolism of blood lipid and inhibit the formation of atherosclerosis caused by hyperlipidemia in rabbits.

Changes in cerebral vessels during experimental hyperlipidemia

Both specific (lipid deposition in endotheliocytes, myocytes, and pericytes) and non-specific (intense formation of apical processes and vacuoles in endotheliocytes and vacuolization of myocytes) changes in cerebral vessels of different diameter were revealed in rabbits and rats after 4 months of experimental hyperlipidemia. These changes suggest reduced endothelium athrombogeneity and intensified transendothelial transport. Biochemical and morphological manifestations of hyperlipidemia in rabbits were more pronounced than in rats.

Dose-dependent hyperlipidemia in rabbits following administration of poloxamer 407 gel

Poloxamer 407 (P-407) is a tri-block polymer that exhibits concentrationdependent reverse thermal gelation, a characteristic potentially useful for developing sustained release injectable drugs. While some reports suggest that P-407 is ‘non-toxic’, rodent studies demonstrate that P-407 induces hyperlipidemia, an action that makes this polymer a questionable drug delivery vehicle. Unfortunately, the majority of earlier studies employed supra-physiologic doses of P-407. The present study examined if lower, clinically useful, doses of gel-forming concentrations of P-407 induced hyperlipidemia in rabbits. Male and female rabbits were injected with 5.5 mg/kg (0.025 mL/kg, 27.5 mg/kg (0.125 mL/kg), or 137.5 mg/kg (0.625 mL/kg) of 22% P-407 and the actions of this polymer on blood chemistry were assessed at 6 h, 1 d,2 d,7 d,and 14 d following injection. Control rabbits received no injection. The highest dose of P-407 (137.5 mg/kg) significantly increased serum triglycerides and cholesterol in both male and female rabbits with the maximum increase observed at 2 d after injection. Male rabbits were more sensitive to P-407 than females following injection of 137.5 mg/kg P-407. The lower doses of P-407 did not alter serum triglycerides or cholesterol. In all groups, serum triglycerides and cholesterol were at baseline levels by 14 d. P-407 did not affect other blood chemistry parameters. Although P-407 induces a dose-dependent hyperlipidemia in rabbits, low doses of this polymer may be used in controlled release drug delivery applications without the untoward hyperlipidemic effect.