Hypolipidemic Effects of 2-Furoic Acid in Sprague-Dawley Rats

2-Furoic acid was shown to be effective in lowering both serum cholesterol and serum triglyceride levels significantly in rats with an elevation of HDL cholesterol level at 20 mg/kg/day orally. LDL receptor activity was reduced in hepatocytes, aorta foam cells, small intestinal epithelium cells and fibroblasts. HDL receptor activity was elevated in the rat hepatocytes and small intestinal cells. These activities were correlated with inhibition of acyl CoA cholesterol acyl transferase activity. Neutral cholesterol ester hydrolase activity was elevated in rat hepatocytes and human fibroblasts. Thus, 2-furoic acid appears to interfere directly with activity of intracellular enzymes rather than affecting high affinity-mediated lipoprotein membrane receptors. In vivo treatment with 2-furoic acid led to reduction in the liver and small intestine ATP dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol 3-phosphate acyl transferase, phosphatidylate phosphohydrolase and heparin induced lipoprotein lipase activities. 2-Furoic acid reduced biliary cholesterol levels but the agent increased bile salts which are lithogenic. Acute toxicity studies in mice suggest that the agent has some hepatic toxicity effects. The LD⁵⁰ was relatively low at 250 mg/kg IP in mice.     

Determination of Oral Bioavailability of Fusaric Acid in Male Sprague-Dawley Rats

Head and neck squamous cell cancer accounts for 3 % of new cancer cases and 2 % of cancer mortality annually in the United States. Current treatment options for most head and neck cancers continue to be surgical excision with or without radiation, radiation alone, or chemotherapy with radiation depending on location, stage of disease, and patient preference. Fusaric acid (FA) is a novel compound from a novel class of nicotinic acid derivatives that have activity against head and neck squamous cell carcinoma (HNSCC). Although its exact mechanism is still unknown, FA is thought to be active by increasing damage to DNA and preventing its synthesis and repair. The novel mechanism of FA provides an alternative to present therapies, as a single agent whether given parenterally or orally. It has synergy with conventional agents taxol, carboplatin, and erlotinib. In order to determine if FA has reasonable oral bioavailability, we have determined the pharmacokinetics of FA in male Sprague Dawley rats following administration by gavage and by intravenous injection. The bioavailability of FA was sufficient (58 %) to suggest that FA may be viable as an orally administered medication. Despite the encouraging bioavailability of FA, the intravenous (IV) pharmacokinetics suggested non-linear behavior within the IV dose range of 10, 25, and 75 mg/kg. These results demonstrate that further pharmacokinetic and toxicity studies in larger animals such as dogs and non-human primates are warranted.     

Negligible Pharmacokinetic Interaction of Red Ginseng and Antihypertensive Agent Amlodipine in Sprague-Dawley Rats

Red ginseng (RG) is the top-selling functional food in Korea, but is not recommended for use in hypertensive patients. This study was performed to determine the pharmacokinetic (PK) interaction between RG and amlodipine, an antihypertensive drug. RG (0, 0.5, 1, or 2 g/kg/d) was administered orally for 2 wk, and then amlodipine (10 mg/kg) was given orally, to Sprague-Dawley (SD) rats. Blood was collected at 0.08, 0.25, 1, 1.5, 2, 3, 6, 12, and 24 h after amlodipine administration. In intravenous (iv) study, RG (0, 1, or 2 g/kg/d) was administered orally to SD rats for 2 wk, followed by amlodipine (2 mg/kg) intravenously (iv). Plasma concentrations of amlodipine were analyzed using a high-pressure liquid chromatography–tandem mass system (LC-MS/MS). Oral administration of amlodipine produced an increase of time to maximum plasma concentration (t_max: 2.6, 4.1, 8.3, and 8.9 h at 0, 0.5, 1, and 2 g/kg/d, respectively), and a decrease of maximum plasma concentration (C_max: 278.5, 212.4, 232.1, and 238.7 ng/ml at 0, 0.5, 1, and 2 g/kg/d, respectively.). However, the area under the concentration–time curve from time 0 to 24 h measurable concentration (AUC_{0-24 h} was 3487.4, 2895.4, 3158.2, and 3495 ng/h/ml at 0, 0.5, 1, and 2 g/kg/d respectively) was not significantly changed among the different dose groups. Administration of amlodipine iv produced no significant changes in the apparent terminal half-life, volume of distribution, and AUC_{0-24 hr} among the different dose groups. These results suggest that RG induced negligible influence on amlodipine pharmacokinetically in rats.     

Metabolism in Rats and Man of Piromidic Acid,a New Antibacterial Agent

1. Metabolism of the antibacterial, piromidic acid (5,8-dihydro-8-ethyl-5-oxo-2-pyrrolidinopyrido[2,3-d]pyrimidine-6-carboxylic acid) was investigated in rats and human subjects. Ten metabolites and the unchanged drug were found in the urine and the bile of both species after oral administration.

2. Metabolites were identified by comparison with authentic materials, except for the unstable metabolite, M-VI, for which a probable structure is proposed. The metabolic pathway of piromidic acid involved hydroxylation in the pyrrolidine ring to give the 2- and 3-hydroxy-derivatives (M-II and M-V). M-II was further metabolized to the corresponding γ-aminobutyric acid derivative (M-IV) and the 2-5-dihydroxypyrrolidine derivative (M-VI) which was further metabolized to the 2-amino-pyridopyrimidine carboxylic acid (M-III). Piromidic acid, M-V, M-II, M-III and M-IV were partly excreted as respective glucuronides.

3. Metabolites, except glucuronides, exhibited antibacterial activity; M-V and M-II showed greater activity than piromidic acid.

4. The metabolism of piromidic acid is discussed in relation to the physico-chemical properties of the drug and its metabolites.     

洛伐他汀降血脂作用的研究

洛伐他汀能够明显降低食饵性高脂大鼠的脂质水平。和对照组相比,治伐他汀60mg／kg·14d－1使血清TC,LDL－C,TC／HDL－C和TG分别下降26．8％（P＜005）,30．0％（P＜0.01）,33．4％（P＜0．01）和19．3％（P＜0．05）,同时还能显著降低肝脏TC（－27．5％,P＜0．01）,TG（－29．8％,P＜0．05）和粗脂肪含量（－51．3％,P＜0．01）。对血清HDL-C无明显影响。在TritonWR1339高脂模型中,洛伐他汀10mg／kg口服二次就能明显降低大鼠血清TC（－32％,P＜0．01）,TG（－13．7％,P＜0．05）和PL（－25．6％,P＜0．01）。     

The Disposition and Metabolism of Acrylic Acid and Ethyl Acrylate in Male Sprague-Dawley Rats

The Disposition and Metabolism of Acrylic Acid and Ethyl Acrylatein Male Sprague–Dawley Rats. DEBETHIZY, J. D., UDINSKY,J. R., SCRIBNER, H. E., AND FREDERICK, C. B. (1987). Fundam.Appl. Toxicol. 8, 549–561. Following oral dosing of [2,3-¹⁴C]acrylicacid (AA; 4, 40, or 400 mg/kg) and [2,3-¹⁴C]ethyl acrylate (EA;2,20, or 200 mg/kg), the dosed radioactivity was rapidly excreted,with 50–75% of the dose for both compounds eliminatedwithin 24 hr. The primary excretory metabolite for both compoundsis carbon dioxide, accounting for 44–68% of the dose.HPLC analysis of the urine of AA- and EA-dosed animals indicatedthe presence of 3-hydroxypropionic acid. The detection of thismetabolite suggests the incorporation of AA into propionic acidmetabolism and may explain the rapid evolution of carbon dioxidefrom AA and EA. HPLC analysis of urine from EA-dosed rats revealedthe presence of two metabolites derived from glutathione conjugation,N-acetyl-S-(carboxyethyl)cysteine and N-acetyl-S-(carboxy-ethyl)cysteineethyl ester. The excretion of the N-acetyl cysteine derivativesof EA, expressed as a percentage of the dosed compound, decreasedin a dose-dependent manner that may be attributed to the depletionof glutathione in organs primarily responsible for glutathioneconjugation. No significant decrease in hepatic nonprotein sulfhydryl(NPSH) content was observed following oral dosing with EA at2–200 mg/kg. However, the depletion of NPSH content atthe dosing site, forestomach, and glandular stomach, decreasedsignificantly between 0.02 and 0.2% EA in the dose solution(2 and 20 mg/kg). This observation would suggest that the dosingsite represents a significant site of conjugation for relativelylow doses of EA. Treatment with the carboxyl-esterase inhibitor,tri-o-cresyl phosphate (TOCP), 18 hr prior to acrylate dosingpotentiated the depletion of hepatic nonprotein sulfhydryls,emphasizing the dominance of hydrolysis as a systemic detoxifyingmode in this species. In contrast to EA, AA did not significantlydecrease NPSH content in the liver, blood, or forestomach atoral doses of <8% AA in the dose solution (400 mg/kg), althougha significant depletion of NPSH was observed in the glandularstomach at doses > 0.08% (4 mg/kg). No conjugation involvingthe double bond of AA could be detected in in vitro reactionswith glutathione or in the in vivo metabolites, suggesting asecondary effect of AA on NPSH content in these organs. Theweights of the forestomach and glandular stomach increased withAA dose, reflecting gross edema and inflammation. With EA thiseffect on organ weight was only demonstrated in the forestomach,and the response was increased when hydrolysis of EA was inhibitedwith TOCP. The effect of AA or EA on stomach weight and NPSHcontent may be attributed to the concentration of these localirritants in the dose solution at the site of dosing.     

二喹啉甲酸检测法测定Sprague-Dawley大鼠肝微粒体蛋白浓度

目的 建立酶标仪检测大鼠肝微粒体蛋白浓度的方法.方法 大鼠尾静脉连续3 d注射0.9%氯化钠注射液2 ml,第4 d解剖大鼠,取肝脏,应用差速离心法提取大鼠肝微粒体,用二喹啉甲酸检测(BCA)法测定肝微粒体蛋白浓度. 结果蛋白标准曲线范围在0~0.5 mg/ml,回归方程为Y=0.091 9+0.868X,(R=0.998).低、中、高浓度回收率分别为101.33%,110.67%,101.17%,日内和日间精密度分别为6.52%, 0.53%, 1.95%和3.01%,7.23%,0.74%.结论 本实验建立的BCA蛋白测定法准确可靠,重复性和稳定性均良好,相比较传统的蛋白测定方法,更为迅速,具有较强的抗干扰的能力,为研究用药后肝微粒体酶活性的改变提供可靠的检测手段.     

Toxicity Studies of Epichlorohydrin in Sprague-Dawley Rats

ABSTRACT

Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, and 46 mg/kg-day, and for 90 days at dose levels of 1, 5, and 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but toxicity, at the higher doses, was evident by: 1) losses in body weight gain and organ weights, 2) reductions in food and water consumption, and 3) in the hematological and microscopic examinations in both study periods. Significant decreases in erythrocyte count, hemoglobin, and hematocrit levels were found in the high dose level in males after 10 and 90 days. Dose-related increases in kidney and liver weights were observed in both sexes at 25 mg/kg-day in the 90-day study and in various organs for both 19 and 46 mg/kg-day in the 10-day study.

Histopathological examination identified the forestomach as the primary target organ for both sexes and in both studies with significant dose-related increases in mucosal hyperplasia (acanthosis) and hyperkeratosis. Based on the data presented, a lowest observable adverse effect level (LOAEL) for oral exposure of Sprague-Dawley rats to epichlorohydrin is 3 mg/kg-day for 10 days and 1 mg/kg-day is suggested as the no observed adverse effect level (NOAEL) for a 90 day oral exposure. These conclusions were the same whether the lesions were analyzed for each sex individually or whether the data in each study was pooled.     

Toxicity Studies of 1,3-Dichlorobenzene in Sprague-Dawley Rats

ABSTRACT

Male and female Sprague-Dawley rats received 1,3-dichlorobenzene daily by corn oil gavage for 10 or 90 consecutive days. The 10-day study doses were 0, 37, 147, 368 and 735 mg/kg; the 90-day study doses were 0, 9, 37, 147 and 588 mg/kg. In the 10-day study, there was a significant depression of body weight in both sexes at 735 mg/kg. Liver weights were significantly increased in both sexes at 368 and 735 mg/kg. Serum cholesterol levels were significantly elevated in both sexes at 368 and 735 mg/kg. Histopathological evaluation revealed centrolobular hepatocellular degeneration at 368 mg/kg in males and 735 mg/kg in females.

In the 90-day study, body weights were significantly depressed in both sexes at 588 mg/kg. Normalization of food and water consumption by final body weight indicated that at 588 mg/kg both sexes had increased food and water consumption relative to controls. Absolute and relative liver weights were significantly increased in both sexes at 147 and 588 mg/kg. Relative kidney weights were significantly higher in both sexes at 588 mg/kg and in males at 147 mg/kg. Serum cholesterol and calcium levels were significantly elevated over controls in females at 37,147, and 588 mg/kg, and in males at all dose levels. Histopathological evaluation at 147 and/or 588 mg/kg demonstrated liver and thyroid lesions in both sexes, and pituitary and kidney lesions in males. A NOAEL was not firmly established.     

The Hypolipidemic Activity of Furoic Acid and Furylacrylic Acid Derivatives in Rodents

2-Furoic acid, 3-furoic acid, 3,4-furan dicarboxylic acid and furyl-acrylic acid were evaluated for hypolipidemic activity in mice and rats. 2-Furoic acid was the most potent agent of the four tested, lowering serum cholesterol levels 41 % and serum triglyceride levels 56 % at 20 mg/kg/day in mice and serum cholesterol 50 % and serum triglyceride levels 42 % in rats. 2-Furoic acid effectively suppressed liver mitochondrial citrate exchange, ATP dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase, phosphatidate phosphohydrolase and hepatic lipoprotein lipase enzymatic activities. Lipid levels after 16 days in mice were reduced in the liver. In the rat cholesterol content of the HDL fraction was elevated and lowered in the chylomicron fraction. 2-Furoic acid administration for 14 days resulted in a large portion of ³H-cholesterol being excreted by the biliary route. The furoic acid derivatives appear to have promise as hypolipidemic agents and further studies on their ability to lower lipids are warranted.     

The Effects of Subchronic Chlorate Exposure in Sprague-Dawley Rats

ABSTRACT

Male and female Sprague-Dawley rats were exposed to drinking water containing 3.0, 12.0 or 48.0 mM sodium chlorate. The mean drinking water consumption varied between exposure groups from 100-200 ml/kg/day. Female exposure groups consistently drank more water (23-42%) than male exposure groups thereby receiving more chlorate/kg/day at every exposure level. There were no compound related deaths; however, both males and females in the high exposure groups had significant weight loss during the 90-day exposure period. Also, in these same groups females had mild but significant decreases in the following relative organ weights; adrenals, thymus and spleen, while the relative brain weight was increased. In males, the heart, kidneys and liver were mildly decreased while the brain and testes were mildly increased. Red blood cell counts and percent hematocrit were decreased in both sexes in the high dose group. Pituitary gland (pars distalis) vacuolization and thyroid gland colloid depletion were prominent in both sexes in mid and/or high dose animals. A NOAEL of 0.36 mM chlorate/kg b.w./day in males and 0.50 mM chlorate/kg b.w./day in females were established.     

Results of Teratogenicity Testing of m-Aminophenol in Sprague-Dawley Rats

Results of Teratogenicity Testing of m-Aminophenol in Sprague-DawleyRats. RE, T. A., LOEHR, R. F., RODRIGUEZ, S. C., RODWELL, D.E., AND BURNETT, C. M. (1984). Fundam. Appl. Toxicol. 4, 98–104.meta-Aminophenol (m-AP) was administered in the diet to femaleSprague-Dawley rats for a period of at least 90 days at levelsof 0.1, 0.25, and 1.0%. In the 0.25% group a significant reductionin body weight was noted, in comparison with control values,and in the 1.0% group a significant reduction in both body weightand food consumption was noted. Ten of the rats in each groupwere necropsied. Deposition of iron positive pigment in thespleen, liver, and kidney combined with decreased red bloodcell count and hemoglobin and increased mean corpuscular volumeindicated a hemolytic effect. There were also morphologic changesin the thyroid which were consistent with hyperactivity. Theremaining 25 rats in each group were removed from m-AP treatmentand immediately mated to untreated males of the same strain.After the mating period the dams again were given m-AP for theduration of gestation. All dams were killed on Day 20 of gestation;one-third of the fetuses were examined for visceral malformationsand two-thirds for skeletal malformations and variations. Anadditional significant reduction in body weight gain was notedduring gestation in the 1.0% group as compared to the controlgroup. There were no other adverse dose-related findings demonstratedin the reproduction performance of the dams or in the survivalor development of their offspring. Therefore, although maternaltoxicity was demonstrated at the highest dose level, there wasno evidence of teratogenic or embryofetal toxicity at any doselevel tested.     

离子型X线造影剂碘羟拉酸的合成

目的离子型X线造影剂碘羟拉酸的合成。方法以5-硝基异酞酸为原料,经酯化、酰胺化、还原、碘化和乙酰化反应等步骤制得碘羟拉酸。结果合成产物经元素分析、核磁共振谱和质谱确证了化学结构。结论该工艺路线方法简便,原料易得,适合工业化生产。     

Ninety-Day Oral Toxicity Study of Dibromochloromethane in Sprague-Dawley Rats

ABSTRACT

Male and female Sprague-Dawley rats received dibromochloro-methane daily by gavage to evaluate its subchronic toxicity. Dose levels were 0, 50, 100, and 200 mg (kg-day)^?1, with 10 animals/ sex/group for 90 consecutive days. Corn oil was used as the vehicle. No changes were found in mortality, clinical signs, ophthalmoscopic examinations, or hematology that were considered to be related to treatment. Mean final body weight and body weight gain (weeks 0–13) were significantly decreased in male and female high dose animals relative to the vehicle control. Food consumption was decreased in males in a dose-related fashion, reaching statistical significance at the highest treatment level. Indications of hepato-toxicity in the clinical chemistry included elevated alanine aminotransferase (mid and high dose males) and alkaline phosphatase (high dose males and females). Increased serum creatinine (mid- and high dose males and high dose females) and decreased potassium (high dose males) were considered to be suggestive of nephrotoxicity. Absolute and relative weights of several organs in male and female animals were depressed and were related to the decreased body weights. The decreases in brain and thymic weights, and increases in liver and kidney weight (female only) were considered to be treatment related. Histopathological changes included findings of lipidosis of the liver and slight to moderate degenerative changes within the proximal tubular cells of the kidney. Based on the results of this study, the (LOAEL) lowest observed adverse effect level for DCBM when administered to Sprague-Dawley rats in corn oil gavage was 50 mg (kg-day)^?1.     

Hypolipidemic Activity of o-(N-Phthalimido)acetophenone in Sprague Dawley Rats

o-(N-Phthalimido)acetophenone has proven to be an effective hypolipidemic agent in rats at 20 mg/kg/ day orally. The agent suppressed the activity of the rate-limiting enzyme of the liver involved in de novo synthesis of triglycerides. The synthetic rate-limiting enzyme for cholesterol esters was also inhibited by the drug in vivo. o-(N-Phthalimido)acetophenone lowered cholesterol in the liver and the aorta wall and generally caused an increase in phospholipids in body tissues. Serum lipoproteins were modulated by the drug with a decrease in cholesterol and triglycerides in the chylomicron, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) and an increase in high-density lipoprotein (HDL) cholesterol. The phospholipid content was increased in the chylomicron, VLDL, and LDL fractions. In hyperlipidemic rats, o-(N-phthalimido)acetophenone lowered elevated blood lipid levels at 20 mg/kg/day orally after 3 weeks of administration. The hypolipidemic rat after drug treatment had a lower LDL cholesterol and a higher HDL cholesterol content, which is therapeutically desirable to protect against cardiovascular disease.     

Twenty-Eight-Day Inhalation Toxicity Study of Silver Nanoparticles in Sprague-Dawley Rats

The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. Thus, the exposed population continues to increase as the applications expand. Although previous studies on silver dust, fumes, and silver compounds have revealed some insights, little is yet known about the toxicity of nano-sized silver particles, where the size and surface area are recognized as important determinants for toxicity. Thus, the inhalation toxicity of silver nanoparticles is of particular concern to ensure the health of workers and consumers. However, the dispersion of inhalable ambient nano-sized particles has been an obstacle in evaluating the effect of the inhalation of nano-sized particles on the respiratory system. Accordingly, the present study used a device that generates silver nanoparticles by evaporation/condensation using a small ceramic heater. As such, the generator was able to distribute the desired concentrations of silver nanoparticles to chambers containing experimental animals. The concentrations and distribution of the nanoparticles with respect to size were also measured directly using a differential mobility analyzer and ultrafine condensation particle counter.     

硫酸乙酐法制备氟嗪酸中间体

用硫酸乙酐混合物作环合剂，制备了氟嗪酸中间体．该方法具有反应条件温和、价格便宜、后处理简单的优点，适用于工业化生产     

Toxicity and Teratogenicity Studies with the Hypolipidemic Drug RMI 14,514 in Rats

Toxicity and Teratogenicity Studies with the Hypolipidemic DrugRMI 14,514 in Rats. Gibson, J.P., Larson, E.J.^A, Yarrington,J.T., Hook, R.H., Kariya, T. and Blohm, T.R. (1981 ).Fundam.Appl.Toxicol. 1:19–25. The hypolipidemic drug RMI 14,514 (5-tetradecyloxy-2-furoicacid) has an oral LD50 of over 5000 mg/kg in rats. In a chronictoxicity study (6 months drug diet) doses of 30,100, or 300mg/kg/day produced no obvious signs of toxicity or abnormalclinical pathology parameters, other than prominent growth retardationat 300 mg/ kg, which was somewhat alleviated when the dose wasreduced to 200 mg/kg after 6 weeks. Hepatic change in the formof mild lipid accumulation was noted histopathologically after6 months of treatment at 100 or 300 mg/kg/day, but was not presentat 3 months or after 4 weeks off drug. The administration ofRMI 14,514 in the diet to pregnant rats at 30, 100, or 150 mg/kg/dayon Days 7 thru 21 of pregnancy (day 1 = day sperm detected)did not induce any teratogenic effects. When rats were exposedto the drug from implantation thru sexual maturity (126 daysof age) at the same dosage, it produced no adverse developmentalor behavioral effects, except for slight reduction in weightgain from birth to sexual maturity at 150 mg/kg/day. The drugcaused reductions in plasma cholesterol and total fatty acids,but no distinct changes in various tissue lipids, except inthe erythrocyte where fatty acids and phospholipids were reduced.These differences did not affect membrane integrity of the erythrocyteas far as osmotic or mechanical fragility tests could determine.The drug, which bears a structural resemblance to long-chainfatty acids, was incorporated into tissue lipids in detectableamounts, but tended to disappear from tissues at a rate similarto that of expected lipid turnover after treatment was stopped.     

Identification of a Subgroup of Sprague-Dawley Rats Highly Sensitive to Drug-Induced Renal Toxicity

Identification of a Subgroup of Sprague-Dawley Rats Highly Sensitiveto Drug-Induced Renal Toxicity. RIVIERE, J. E., DIX, L. P.,CARVER, M. P., AND FRAZIER, D. L. (1986). Fundam. Appl. Toxicol.7, 126-131. Laboratory rats available from breeding facilitiesare usually assumed to be homogeneous populations within eachstrain; however, previous studies in our laboratory suggestedthat there may be a subgroup of Sprague-Dawley rats which arehighly sensitive to aminoglycoside nephrotoxicity. The presentstudy clearly identifies a subpopulation of Sprague-Dawley ratswhich was highly sensitive to nephrotoxicity from supratherapeuticdoses (75 mg kg^–1 day^–1) of the aminoglycoside antibioticgentamicin. Gentamicin was administered subcu-taneously in adivided regimen, 25 mg/kg every 8 hr, for 7 days. Statisticalanalysis of post-treatment serum creatinine (SCR) and urea nitrogen(SUN) concentrations demonstrated two distinct populations:normally responding rats (SCR=1.92±0.54 mg/dl, SUN=71.5±18.4mg/dl, N=87) and highly sensitive rats (SCR=4.10±0.83mg/dl, SUN=146.4±24.9 mg/dl, N=12) (mean±SD).Comparison of predosing blood and serum chemistries betweenthese two populations revealed statistical differences onlyin initial serum osmolality, oxygen tension, and total protein.Since there is a subpopulation of humans which are at risk fordeveloping aminoglycoside nephrotoxicity due to unknown hostfactors, these highly sensitive Sprague-Dawley rats may providean animal model for investigating this human clinical problem.