A study of atherosclerosis regression in Macaca mulatta. I. Design of experiment and lesion induction.

Rhesus monkeys were fed an atherogenic diet containing 40% of calories from lard and 1.0 mg/Cal cholesterol for either 19 months (Colony I) or 38 months (Colony II). At the end of the induction period the animals from each colony were divided into three groups (A, B, C) on the basis of total plasma cholesterol concentration during the induction period. Group A animals were killed at the end of the induction period for baseline observation of the extent and severity of atherosclerosis. Group B from each colony was fed a diet which maintained total mean plasma cholesterol concentrations between 280 to 320 mg/dl comparable to human beings with modest hyperlipoproteinemia. Group C from each colony was fed a diet which maintained total mean plasma cholesterol concentrations between 180 to 220 mg/dl, comparable to people who had modest hyperlipoproteinemia but were able to reduce plasma cholesterol concentrations by approximately 100 mg/dl using diet or drugs. Each group was further divided into two subgroups (B₁, B₂, and C₁, C₂). Animals from subgroup 1 were fed these diets for 24 months and animals from subgroup 2 were fed the same diet for 48 months.This report describes the clinical history, chemical analyses of arteries and the morphological extent and severity of atherosclerosis in arteries from animals of both colonies at the end of the induction period.     

猕猴脑动脉硬化造型过程中血清脂质的变化

高脂高胆固醇喂养幼年(2—4岁)和成年(10—13岁)雄性猕猴16—17个月,并辅以服用甲基琉氧嘧啶。实验结果,发现第二个月的胆固醇水平超过250mg%,并持续到实验结束。低密度脂蛋白—胆固醇(LDL—C),伴随着总胆固醇升高而升高,甘油三酯(TG)和高密度脂蛋白—胆固醇(HDL—C)变化不大。幼年和成年组之间无显著性差异。     

Resveratrol increases serum adiponectin level and decreases leptin and insulin level in an experimental model of hypercholesterolemia

Serum adiponectin concentration is inversely associated with leptin and insulin concentration. There is little paucity of information in the literature on the adipokine levels and regulation by resveratrol in cholesterol diet-fed animals. Thirty rabbits were randomly divided into six groups, each of five animals: Group 1 = control (C), Group 2 = cholesterol diet (CD) only, Group 3 = resveratrol 200?mg/kg (R200), Group 4 = resveratrol 400?mg/kg (R400), Group 5 = CD + R200, Group 6 = CD + R400. The preparations were administered for 8th weeks of the treatment protocol. weight and blood glucose level were measured on week zero and the 8th week of the treatment. At the end of the study period, the rabbits were placed under light anaesthesia. Blood samples were evaluated for serum concentrations of metabolites assays (adiponectin, leptin and insulin). Serum adiponectin significantly (P < 0.05) increased in resveratrol + CD groups, compared to CD group only. Leptin and insulin significantly (P <0.05) decreased in CD groups co-administered with resveratrol, compared with CD group only. In conclusion, the increase in adiponectin level and decrease in leptin and insulin level following resveratrol administration elucidated the therapeutic potential of resveratrol, despite cholesterol diet consumption.     

丝瓜络对实验性高血脂大鼠的降血脂效应

目的:探讨中药丝瓜络(RLF)对实验性高血脂大鼠的降血脂效果,以及对实验大鼠体重的影响。方法:雄性SD大鼠32只,随机均分为4组:对照(A)组、高脂模型(B)组、高脂+丝瓜络(C)组、丝瓜络(D)组。 A组和D组大鼠每日饲基础饲料,B组和C组给予高胆固醇饲料,C组和D组的大鼠每日经胃灌服丝瓜络煎剂10 mL/kg BW,A组和B组为每日每只经胃灌服饮用水2 mL,实验周期为14 d。结果:(1)实验后B组大鼠的血清胆固醇(TC)和甘油三脂(TG)分别为(4.63±1.10)和(1.13±0.15) mmol/L,显著高于对照(A)组的TC 和 (P<0.01), 而C组的TC 和TG 则显著低于B组(分别为P<0.05及P<0.01);(2)D组大鼠的TC,实验后较给药前有显著降低(P<0.01);(3)在实验的第8d,B组大鼠的血清高密度脂蛋白胆固醇(HDL-C)为(0.61±0.11) mmol/L,显著低于A 组 (P<0.01),而C组HDL-C 与A组没有显著差异(P>0.05);(4)B组大鼠体重实验后显著增加,而 C组的体重在变化与A组相似。结论:丝瓜络对实验性高血脂大鼠有明显的降血脂效应,使实验大鼠的TC和TG显著降低,HDL-C显著升高,而且能显著减轻实验大鼠的体重。     

Effects of dietary cholesterol and voluntary exercise on histopathology,plasma and hepatic lipids of the male rat

Summary To avoid the stress of imposed activity, male weanling rats were allowed to exercise voluntarily in individual activity wheels. The exercising animals, which were compared to sedentary controls, ran over 26 km/wk (over 2 miles/day). Half of the animals in each group were fed a 10% coconut oil diet; the other half were fed the same diet with 1% added cholesterol.Plasma cholesterol was monitored throughout the 23-week regime. Consistently lower plasma cholesterol values were shown by the exercising animals during the first weeks of the study, the differences being statistically significant at the end of the 8th week. Dietary cholesterol sharply elevated plasma cholesterol, which reached a peak at the 5th week, then declined to basal levels by the 10th week.Both neutral glycerides and cholesterol levels of the livers were elevated considerably by the addition of cholesterol to the diet. Exercising, however, had a lowering effect on both liver cholesterol and neutral glycerides. The weights of the hearts of the exercising rats were increased, while those of the other organs selected were unchanged.Histologic examination of sections of livers showed fat infiltration of hepatic cells varying in severity, depending on the diet. Greater damage to liver cells was noted when cholesterol was added to the basal diet. Fat infiltration was lessened considerably in exercising rats on the basal diet; exercising partially overcame the effects of added cholesterol.This work was supported in part by Grant-In-Aid from The Nutrition Foundation, Inc.; State of Washington Initiative 171 Fund and USPHS Research Grant HD-03475 from the National Institutes of Health.     

厚朴酚对高脂饮食性肥胖大鼠体重及胰岛素抵抗的影响

目的 观察厚朴酚对高脂饮食性肥胖大鼠体重和血清生化指标的影响,并探讨其机制.方法 将SD大鼠随机分成4组:对照组,高脂组和厚朴酚高、低二个剂量组.每天定时称量食水、灌胃,每周测体重,第8周末各组大鼠禁食12 hA股动脉取血测定血清生化指标.结果 低剂量厚朴酚组从第4周开始体重比高脂组显著降低(P＜0.05),高、低剂量厚朴酚组的胰岛素、游离脂肪酸、丙二醛以及低剂量组的血糖、三酰甘油比高脂组都显著下降(P＜0.05).结论 厚朴酚能降低高脂饮食性肥胖大鼠的体重,并对胰岛素抵抗和糖脂代谢紊乱等有一定的改善作用.     

Enhancement of cholesterol and cholesteryl ester accumulation in re-endothelialized aorta.

The purpose of the experiments reported here was to determine chemically the character and quantity of lipid in re-endothelialized and de-endothelialized areas of rabbit aortas. The aortas of 22 rabbits, Groups I and II, were de-endothelialized with a balloon catheter, and the rabbits were maintained on a lipid-poor diet for 4 weeks. Thirteen rabbits, Group II, were then fed an egg-supplemented diet for 6 weeks. Nine rabbits, Group I, were continued on the lipid-poor diet for an additional 6 weeks. Control rabbits with uninjured aortas were fed a lipid-poor diet for 10 weeks (Group III) or an egg-supplemented diet for 6 weeks (Group IV). Nonesterified cholesterol and fatty acids, cholesteryl esters, triacylglycerols, and squalene were quantitated in re-endothelialized and de-endothelialized aorta by thin-layer chromatography and fluorometric analysis. The results indicate 1) that there was approximately three times as much nonesterified cholesterol and cholesteryl ester in re-endothelialized aorta of Groups I and II as compared with adjacent de-endothelialized aorta and 2) that in re-endothelialized aorta of Group II the amount of total cholesterol correlated with serum cholesterol concentration in contrast to adjacent de-endothelialized aorta, with no correlation over a range of nearly 900 mg/100 ml. These studies indicate that the presence of endothelium favors accumulation of aortic cholesteryl esters. The results suggest that arterial lipid accumulation is not simply a result of passive filtration but may result from metabolic differences in the re-endothelialized neointima.     

三种多孔磷酸钙骨水泥体外研究比较

目的：探讨以不同方法制备的三种多孔磷酸钙骨水泥（Calcium phosphate cement, CPC）的理化特性、生物相容性及强度的差异.方法：将20wt%甘露醇（A组）、5wt%碳酸氢钠（B组）及5wt%明胶微球（C组）分别与CPC粉末混合固化制备多孔CPC.生理盐水浸泡1周、4周后,测定材料孔径率及抗压强度,电镜观察材料断面,X线衍射法检测CPC的转化情况.成骨细胞接种于各组CPC支架上,扫描电镜观察细胞形态;三组材料浸提液分别与成骨细胞共培养3 d,MTT法测定细胞增殖率,试剂盒检测碱性磷酸酶水平.结果：浸泡1周后C组孔径率稍低,4周后各组无明显差异;但两个时间点C组强度均最高.材料断面扫描A组孔径较大、连通性欠佳,B组孔径极不规则且分布不均匀,C组孔径规则、连通性好.1周后X线衍射显示三组均出现羟基磷灰石衍射峰;4周后C组羟基磷灰石衍射峰最强,磷酸四钙衍射峰最弱.成骨细胞在各组材料上生长良好,但C组细胞量最多,细胞增殖及碱性磷酸酶水平明显高于其他两组.结论：以明胶微球制备的多孔CPC具有较高的初始强度及较好的生物相容性,可作为非负重部位骨替代材料.     

Lowering of lipid composition in aorta of guinea pigs by Curcuma domestica

Background

A short-term study was carried out using guinea pigs to determine the effects of Curcuma domestica on lipid composition in the serum and aorta.

Methods

Animals were given food pellets containing 4% (w/w) powdered rhizome of C. domestica in order to determine its effect on cholesterol, triglyceride and phospholipid levels in the aorta and serum. The animals were fed either a cholesterol free diet or a high cholesterol diet (2% cholesterol, w/w, in food pellet) in order to induce hypercholesterolemia.. After five weeks of this diet treatment, blood and aorta were taken for biochemical analysis and histological studies.

Results

C. domestica in the diet showed no significant effect on the levels of cholesterol, triglyceride and phospholipid in the serum and aorta of the cholesterol free diet animals. However, addition of C. domestica to a high cholesterol diet counteracted increases in the levels of cholesterol, triglyceride and phospholipid in the aorta. Histology studies showed less cholesterol deposits in the aorta of high cholesterol diet animals given C. domestica compared to the high cholesterol diet animals not given C. domestica supplement. C. domestica also had a lowering effect on triglyceride level in the serum of high cholesterol diet animals but showed no effect on serum cholesterol and phospholipid levels.

Conclusion

This study has shown that dietary intake of C. domestica decreased all lipid composition levels in the aorta and also the serum triglyceride level. In addition, C. domestica also reduced cholesterol deposition in the aorta of high cholesterol diet animals.     

Self-expandable nitinol stent placement in homocysteinemic porcine aorta

PURPOSE: To compare aortic intimal thickening of normal and hyperhomocysteinemic pigs (induced with a methionine-rich diet) following placement of a self-expanding nitinol stent. METHODS: Eighteen Macau pigs were used. They were older than eight weeks in age and had an average weight of 30 kg. Pigs were randomly divided into two groups. The first, Group C (control), was fed a regular diet, and the second group, Group M, was fed a methionine-rich diet for 30 days to induce hyperhomocysteinemia. The self-expandable nitinol stents were 25mm in length and 8 mm in diameter after expansion. Blood samples were collected to measure total cholesterol, triglycerides, HDL and homocysteine concentrations. All animals were subjected to angiography. Thirty days after the procedure, the animals were sacrificed, and the abdominal aorta was removed for histological and digital morphometry analysis. RESULTS: Under microscopic evaluation, the intima was significantly thicker in Group C than in Group M. When groups were compared by digital morphometric analysis, intimal thickening of the vessel wall was higher in Group C than in Group M. There was no significant change in total cholesterol, triglycerides or HDL concentrations in either group. In group C the levels of plasma homocysteine ranged from 14,40 to 16,73 micromol/l; in Group M, plasma homocysteine levels ranged from 17.47 to 59.80 micromol/l after 30 days of a methionine-rich diet. CONCLUSION: Compared to normal pigs, less intimal hyperplasia was observed in the abdominal aortas of hyperhomocysteinemic pigs thirty days after the insertion of a self-expandable nitinol stent.     

Atheroarteriosclerosis induced by infection with a herpesvirus.

Atheroarteriosclerosis closely resembling that in humans was induced in normocholesterolemic and hypercholesterolemic chickens by infection with Marek's disease herpesvirus (MDV). Four comparably sized groups of chickens were used. Each group was initially fed a diet relatively poor in cholesterol. Group I and II were inoculated intratracheally at 2 days of age with MDV. At 15 weeks, one group of virus-infected chickens (Group II) and one group of uninfected controls (Group IV) were fed a 2% cholesterol supplement for an additional 15 weeks. Group I, infected, and III, uninfected, were continued on a cholesterol-poor diet. All groups were killed at 30 weeks. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of both Groups I and II but not in those of Groups III and IV. Microscopically, arterial changes in infected animals were characterized by occlusive fibromuscular intimal thickening, which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in humans. These results may be important to our understanding of human arteriosclerosis, since there is widespread and persistent infection of human populations with as many as five herpesviruses.     

Flow cytometric quantification of cholesteryl ester-containing "foam" cells. II. Analysis of aortas from cholesterol-fed swine

We have examined foam cell accumulation in abdominal and thoracic aortic segments of swine with experimentally induced atherosclerosis. Young (less than 1-year-old) male swine were divided into four groups that were fed control, lard (20%), lard (20%) plus cholesterol (1%), and regression (3 months cholesterol-lard followed by 3 months control) diets for 6 months. Aortas were removed from animals and enzymatically dissociated. Foam cells were detected by specifically staining their cholesteryl ester inclusions with the fluorescent dye filipin. Flow cytometry was used to quantify the number of foam cells in each aortic cell suspension. Cholesterol-lard feeding increased serum cholesterol levels 6-fold and induced a substantial increase in both abdominal and thoracic foam cell densities. Lesion development in cholesterol-lard-fed animals, as assessed by macroscopic evaluation of aortas, correlated with foam cell accumulation as determined by flow cytometry. Accumulation of foam cells was extremely variable from animal to animal and did correlate significantly with serum cholesterol but not with serum triglyceride levels. Interestingly, although serum cholesterol levels increased 1.5-fold in swine fed the lard diet, foam cells did not increase significantly as compared to control animals. Animals placed on a control diet following 3 months of the cholesterol-lard diet showed a trend toward lower foam cell densities as compared to animals fed the cholesterol-lard diet for the entire 6 months. Flow cytometric analysis of filipin-stained aortic foam cells provides a new means to evaluate atherosclerotic lesion development.     

Vitamin E attenuates homocysteine and cholesterol induced damage in rat aorta

BackgroundThe aim of this study was to investigate the effect of vitamin E on homocysteine and cholesterol-induced damage of rat aorta.MethodsWistar rats (all fed with a vitamin E poor diet) were divided into five groups. Control group was fed with the diet only, the second group received 1 mg kg^?1 day^?1 l-methionine in drinking water, the third group was fed with 2% cholesterol containing diet, the fourth group received l-methionine and cholesterol together, and the fifth group was fed with l-methionine and cholesterol and received intramuscular injections of vitamin E. After 4 weeks serum homocysteine, cholesterol and vitamin E levels were measured; aortas were removed; collagen and elastin and the major extracellular matrix components were evaluated microscopically as indicators of aortic degeneration. Aortic collagen content was measured by a colorimetric hydroxyproline assay.ResultsFour-week diet supplementation with methionine and cholesterol caused a twofold increase in serum homocysteine and 22% increase in serum cholesterol levels; endothelial damage and degenerative alterations in the aortic media were observed, as indicated by the dissociation of elastic fibers and accumulation of collagen. Vitamin E completely prevented the accumulation of collagen and largely prevented aorta damage as shown by the morphological data.ConclusionThe results indicate that, even moderate increases in homocysteine and cholesterol levels are sufficient to induce vascular degeneration that may be prevented by vitamin E supplementation.     

Protective effect of grape seed proanthocyanidins against cholesterol cholic acid diet-induced hypercholesterolemia in rats

BackgroundDietary cholesterol plays an important role in the development of atherogenesis and cardiovascular diseases. We explored the prospective effect of grape seed proanthocyanidins in controlling hypercholesterolemia induced oxidative injury and apoptosis in atherogenic animals.MethodsFour groups of male Wistar rats (250–300 g) were used for the study. Group I served as control and received vehicle (saline) alone, Group II served as the induction group fed with a high-cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid—CC diet) for 30 days, Group III served as drug control and was treated with grape seed proanthocyanidins (100 mg/kg body weight) orally for 30 days, and Group IV animals were fed with CC diet for 30 days along with grape seed proanthocyanidins (100 mg/kg body weight) orally.ResultsCC diet induced an abnormal increase in lipid peroxidation, tissue cholesterol, triglyceride, serum low-density lipoprotein, and very low density lipoprotein, and decreased the high-density lipoprotein concentration. Altered activity of cardiac and serum creatine kinase, accompanied by a decreased cardiac enzymatic and nonenzymatic antioxidant defense system and an increase in the expression of cytochrome c and caspases-3, was observed in CC diet-fed rats. These changes were partially restored in the grape seed proanthocyanidin-treated group.ConclusionGrape seed proanthocyanidins have cardioprotective effects against CC diet-induced hypercholesterolemia via their ability to reduce, directly or indirectly, free radicals in the myocardium.     

Experimental atherosclerosis in swine: effect of dietary protein and high fat

Two groups of pigs each consisting of 6 animals were fed for 18 months on isocaloric amounts of an experimental diet with a high fat content and cholesterol but with widely different levels of protein (5% vs. 25% by weight of the diet). In addition, a third group consisting of 4 animals was maintained on normal stock diet to serve as control.Animals of the low protein group showed the maximal intimal surface area involvement with atherosclerotic lesions in the aorta and coronary arteries, and also the most severe among the three groups. No significant differences were noted in the extent and severity of lesions between the high protein-high fat fed animals as compared with the high protein-low fat fed controls. Lesions of the low protein group had a higher cholesterol content and a raised cholesterol:phospholipid ratio than those in the other two groups.Extremely low levels of dietary proteins seem to have had a promotive effect on the induction of atherosclerotic lesions by an atherogenic diet, whereas adequate levels of dietary proteins have had a protective influence. The precise mechanism by which varying levels of dietary proteins have such effects is not understood. It may possibly be related to the aberrations of lipid metabolism induced by extremely low levels of dietary proteins.     

EFFECT OF HYPERLIPIDEMIA ON GLOMERULAR SCLEROSIS IN UNILATERAL NEPHRECTOMIZED RATS

The development of focal segmental glomerular sclerosis (FSGS) and its relation to hypertriglycemia were studied in unilateral nephrectomized rats. Group A (n=6), fed standard rat chow supplemented with 20% beef tallow and 0.6% cholic acid for 25 weeks, showed evidence of hypertriglycemia (109.4 ±4.3 mg/dl). Group B (n=7) was given the same rat chow as group A, but they did not have high serum levels of TG (66.4 ±2.3 mg/dl). Group C (n = 6) were the controls and their serum TG levels were 53.0 ±3.8 mg/dl. The incidence of FSGS and body weight was significantly higher in group A than in groups B (<0.01) and C (<0.05). In all three groups, rats with over a 4% FSGS revealed significantly high serum TG levels, proteinuria, and body weight, as compared with rats with less than 1% of FSGS. The serum cholesterol levels did not correlate with the incidence of FSGS. We tentatively conclude that hypertriglycemia induced by a diet rich in saturated fatty acid may play an importent role in the production and progression of FSGS.     

Effect of hyperlipidemia on glomerular sclerosis in unilateral nephrectomized rats

The development of focal segmental glomerular sclerosis (FSGS) and its relation to hypertriglycemia were studied in unilateral nephrectomized rats. Group A (n = 6), fed standard rat chow supplemented with 20% beef tallow and 0.6% cholic acid for 25 weeks, showed evidence of hypertriglycemia (109.4 +/- 4.3 mg/dl). Group B (n = 7) was given the same rat chow as group A, but they did not have high serum levels of TG (66.4 +/- 2.3 mg/dl). Group C (n = 6) were the controls and their serum TG levels were 53.0 +/- 3.8 mg/dl. The incidence of FSGS and body weight was significantly higher in group A than in groups B (p less than 0.01) and C (p less than 0.05). In all three groups, rats with over a 4% FSGS revealed significantly high serum TG levels, proteinuria, and body weight, as compared with rats with less than 1% of FSGS. The serum cholesterol levels did not correlate with the incidence of FSGS. We tentatively conclude that hypertriglycemia induced by a diet rich in saturated fatty acid may play an important role in the production and progression of FSGS.     

Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo

Bacteria and viruses are suspected to induce arteriosclerosis; however, most investigators have focused on coincidences rather than causal relationships. The aim of this work was to establish a rabbit model in which the vessel reaction to local perivascular injection of defined bacterial products can be analyzed. A total of 23 rabbits were randomized to four groups. Groups A and B were fed a normal diet, groups C and D were fed a cholesterol-enriched diet. Groups A and C were treated with a single perivascular injection of bacterial lipopolysaccharide (LPS, endotoxin) placed next to auricular, carotid and femoral arteries, and sodium chloride placed next to the contralateral arteries (control). Group B and D animals were treated with repeated perivascular injections over 90 days. Vascular tissues (n=116 treated segments of 23 rabbits) were analyzed using morphometry at histology, and using immunohistochemistry to detect macrophages, lymphocytes and vascular smooth muscle cells. LPS treatment resulted in transient focal intima thickening. After single LPS application, no increase in atheromatous lesion formation was observed in comparison with controls (group C, lesion area index 0.031+/-0.012 vs 0.015+/-0.006, P=1.0). Repeated LPS application resulted in significant atheromatous lesion formation compared with saline control (group D, lesion area index 0.148+/-0.049 vs 0.008+/-0.006, P=0.003) in hypercholesterolemic rabbits. Repeated LPS inflammation in normocholesterolemic did not lead to atheromatous lesion formation (intima media ratio 0.04+/-0.01 vs 0.04+/-0.007, P=1.0). Single perivascular administration of low-dose bacterial LPS resulted in transient focal intimal thickening, while significant increase in lesion formation occurred after repeated LPS application in cholesterol-fed animals. In conclusion, this animal model will allow the assessment of the impact of defined dosages of different bacterial pathogens onto the vascular wall in the context of atherogenesis. The atheromatous lesion-promoting effect of repeated perivascular administration of LPS supports the hypothesis that bacterial pathogens may be involved in atherogenesis.     

不同脂肪含量的高脂纯化配方饲料对大、小鼠代谢综合征发生的影响

 摘要： 目的 探讨不同脂肪含量的高脂纯化配方饲料对大、小鼠体重、血糖、血胰岛素、血脂、脂肪肝及白蛋白尿的影响。 方法 雄性SD大鼠及C57BL/6小鼠随机分为MS10%、MS45%和MS60%脂肪含量饲料组,喂养3个月,检测动物体重、血糖、血胰岛素水平、血脂和蛋白尿水平,以及主要脏器重量及肝脏脂质含量。 结果 与正常组（MS10%脂肪含量）相比,高脂组（MS45%和MS60%脂肪含量）动物体重显著增加,出现明显的糖耐量异常、胰岛素抵抗和血脂水平升高,同时伴有肝脏脂质含量和蛋白尿水平的增加,并且以MS45%高脂组体重增加及胰岛素抵抗更加显著。 结论 MS45%和MS60%高脂配方饲料均可在大、小鼠较好地诱导代谢综合征的发生,而且前者优于后者。 关键词： 高脂饲料;胰岛素抵抗;肥胖;代谢综合征     

Ethanol-induced alterations in the morphology and function of the rat ovary

The purpose of this study was to compare the effects of different dosages of ethanol on ovarian morphology and function. Holtzman rats, 20 days old, were divided into groups as follows: The rats in Group I were autopsied at 20 days of age, and those in Group II were placed on ad libitum chow and water diet; the rats in Groups III and V were fed on a liquid diet containing 2.5% or 5% ethanol respectively; Groups IV and VI were pair-fed controls to Groups III and V, respectively. Rats in Groups II, III, IV, and VI were maintained on the diets for 50–55 days and killed at late proestrus-estrus, while the animals in Group V did not exhibit estrous cycles and were killed on day 55 of treatment. The average increase in body weights of rats in Groups II, III, and IV was significantly greater than the increase in body weights of rats given 5% ethanol or their pair-fed controls. In the rats treated with 5% ethanol, vaginal opening was significantly delayed from the controls, estrous cycles were absent, ovarian weights were similar to those of the 20-day-old rats, ovaries contained corpora lutea of only one estrus, uteri weighed less than controls, and histologically, the uteri and vaginae were similar to those of 20-day-old rats. However, in the rats treated with 2.5% ethanol, all of the parameters were similar to those of the controls. The average serum alcohol level for the rats on the 5% ethanol diet was 249 mg%; the serum alcohol levels were at the lower limit of detection for the rats on the 2.5% ethanol diet. The data show that ovarian function was suppressed in the rats that received the 5% ethanol but not in rats on the 2.5% ethanol diet.