Rat Large Intestine Research Articles

Expression and localization of clusterin mRNA in the small and large intestine of the irradiated rat: its relationship with apoptosis.

Apoptotic elimination of intestinal cells following irradiation has been studied in the small and large intestine of the rat, and correlated with the level of expression and localization of clusterin mRNA. Clusterin was moderately expressed in normal intestine where only small levels of apoptosis were found. After irradiation, however, there was a temporal correlation between an increased apoptotic index and increased clusterin expression. Localization of clusterin mRNA by in situ hybridization identified extensive labelling in the lower part (Paneth cell region) of small intestinal crypt, whereas epithelial cells in the large intestine were diffusely labelled. Clusterin expression was not localized over apoptotic cells and its role may be as a cell protection factor for surviving cells, as had been suggested by others. Clusterin may also be involved in remodelling of the intestinal crypt after radiation damage, a process that includes altering cell-to-cell contact, apoptosis, and sloughing of the dead cells from the intestinal villi. Our results do show a close temporal link between apoptosis and clusterin expression, and, as such, expression of the gene may be a useful indicator of presence of apoptosis in the irradiated intestine.

Effectiveness and toxicity screening of various absorption enhancers in the large intestine: intestinal absorption of phenol red and protein and phospholipid release from the intestinal membrane.

The effectiveness and local toxicity of absorption enhancers on the absorption of phenol red (PR) from the large intestine of rats were examined using an in situ loop method. The absorption enhancers used in this study were sodium glycocholate (GC-Na), sodium taurocholate (TC-Na), sodium deoxycholate (DC-Na), EDTA, sodium salicylate (Sal-Na), sodium caprate (Cap-Na), diethyl maleate (DM), N-lauryl-beta-D-maltopyranoside (LM) and mixed micelles (MM), all used at a concentration of 20 mM. Local toxicity was also investigated by assessing protein and phospholipid release as biological markers. DC-Na and MM were the most effective absorption enhancers, but they caused considerable release of proteins and phospholipids. GC-Na, TC-Na and LM, which caused little or only slight membrane damage, promoted PR absorption. Sal-Na, DM and EDTA did not enhance PR absorption. Overall, a correlation exists between the area under the curve of PR and protein and phospholipid release in the presence of absorption enhancers. However, GC-Na, TC-Na and LM promoted the absorption of PR with low toxicity. From these results, we concluded that GC-Na, TC-Na and LM are effective absorption enhancers which have low levels of toxicity at a concentration of 20 mM.

Dietary cellulose improves decreased muscular layer weight of the large intestine in rats fed the diet containing polydextrose

We compared the effects of dietary polydextrose, cellulose and guar gum on muscular weight of the large intestine in rats and investigated effects of dietary cellulose and kaolin supplemented to the polydextrose diet on the muscular weight of large intestine in rats. Animals were fed the same amount of a diet for either 1 or 5 wk containing 7 g/100 g of polydextrose, cellulose or guar gum, or a diet which was made by mixing 1 part of cellulose or kaolin with 9 parts of the polydextrose (7 g/100 g) diet. The feeding of polydextrose diet for either 1 or 5 wk caused less large intestinal weight and muscular weight of the large intestine compared to the cellulose and guar gum diets. Feeding the kaolin-added polydextrose diet for 1 wk and 5 wk increased large intestinal weight and its muscular weight compared to feeding the polydextrose diet, however the 1 wk feeding was not long enough to increase those to the same level for the cellulose and guar gum dietary groups. Feeding of the cellulose-added polydextrose diet for 1 and 5 wk increased large intestinal weight and its muscular weight up to the same level for the cellulose and guar gum dietary groups. These results indicate that although dietary poly-dextrose decreases the muscular weight of large intestine in rats, supplementation of cellulose to the polydextrose diet can effectively overcome the effect of dietary polydextrose on the muscular weight of large intestine.

Differences in epithelial apoptosis and apoptosis-related gene expression between the rat small and large intestine

Differences in epithelial apoptosis and apoptosis-related gene expression between the rat small and large intestine

Structure and genetic polymorphism of blood group A-active glycosphingolipids of the rat large intestine.

Study of blood group A- and B-active glycosphingolipid content of the epithelium of the large intestine of 16 strains of inbred rats led to the discovery of two related strains, SHR and WKY, devoid of A-active glycolipids, whereas all strains expressed B-active glycolipids. This finding evidenced a new A/non-A genetic polymorphism in the rat. Blood group A-active glycolipids were isolated from the large intestine of F344 rats and purified by affinity chromatography on immobilized Helix pomatia lectin. Three glycolipid fractions were separated by preparative thin-layer chromatography and characterized by electron-impact mass spectrometry of their permethylated and permethylated-LiAlH4-reduced derivatives. They were identified as a tetraglycosylceramide (A-4), a hexaglycosylceramide (A-6), and a difucosylated heptaglycosylceramide (A-7) with small amounts of monofucosylated octaglycosylceramide (A-8). Methylation analysis and fragmentation indicated that A6 and A-8 had a lacto- and A-7 a neolactotetraosylceramide core, respectively, identical to the core structures of B-6 and B-7 previously characterized in the large intestine of WF rats (Angström et al. (1987) Biochim. Biophys. Acta 926, 79-86). Upon methylation analysis, B-6 and B-7 purified from SHR (A-deficient) and F344 (A-expressing) were found identical to those of WF rats. This result indicated that precursor substrates for the synthesis of A-active glycolipids were available in SHR rats and thus the genetic deficiency of A-active glycolipid expression probably originated in a defect of the termination of the blood group A determinant by the alpha-3-N-acetylgalactosaminyltransferase.

High-performance liquid chromatography—thermospray mass spectrometry of ω-hydroxy polyunsaturated fatty acids from rat brain homogenate

A method for the analysis of ω-hydroxy polyunsaturated fatty acids (ω-HPUFAs) in rat tissue homogenate, supplemented with NADPH and homo-γ-linolenic acid [20:3( n − 6)], arachidonic acid [20:4( n − 6)], eicosapentaenoic acid [20:5( n − 3)] or docosahexaenoic acid [22:6( n − 3)] as a substrate was developed. By ion analysis of chromatograms obtained with reversed-phase HPLC—thermospray MS, many ω-HPUFAs corresponding to each precursor fatty acid could be characterized by the high intensity of the molecular ion (MH +) and quasimolecular ion (MNH + 4, MNa +), while other common HPUFAs were characterized by the high intensity of the base ion of MH + − H 2O. On a selected-ion monitoring chromatogram of rat brain homogenate, significant amounts of ω-HPUFA from each precursor fatty acid, especially from 22:6( n − 3), were detected compared with the amounts found in rat large intestine homogenate. Based on these results, a highly active NADPH-dependent ω-oxidation system is suggested for rat brain homogenate resulting in extensive oxidation of 22:6( n − 3).

Pharmacological effect of recombinant human colony-stimulating factor (rhG-CSF) after administration into rat large intestine

The effects of organic acid and nonionic surfactant on the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after administration into the large intestine of rats was investigated in comparison with administration into the small intestine. RhG-CSF was administered to rats (50 and/or 100 μg/kg) as solutions in which citric acid and/or polyoxythelated castor oil derivative (HCO-60) were formulated as representative of both organic acid and nonionic surfactant, respectively. Test solutions were administered into the rat ascending colon or duodenum. Blood samples were collected for a 72 h period from the rat tail artery and the blood total leukocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The results are expressed as a relative increase in BTL counts as compared to the pre-dose level. The area under the curves (AUC; % BTL increase × h) obtained was used as an index for the pharmacological activity of rhG-CSF when comparing the test with the placebo solution. With respect to large intestinal administration, the following observations were made: (1) the effect of citric acid on the pharmacological activity was dependent on the amount of citric acid added to the test solution; (2) HCO-60 exerted a synergistic effect to the critic acid on the pharmacological activity of rhG-CSF; (3) dose-dependent pharmacological activity of rhG-CSF was achieved at 50 and 100 μg/kg. As compared to small intestinal administration, stronger pharmacological activity of rhG-CSF was elicited by administration into the large intestine. These results are in support of the potential use of colonic delivery of rhG-CSF as an oral dosage form.

Carrier-mediated transport is involved in mucosal succinate uptake by rat large intestine.

Mucosal uptake of succinate across the luminal epithelial border in various segments of the large intestine of the rat (proximal and distal colon, caecum) was investigated using an in vitro mucosal uptake technique. For comparison, some experiments with jejunal preparations were also performed. Additionally, disappearance of succinate from the lumen of ligated loops of the proximal and distal colon was measured in vivo. In the ligated loop experiments, the succinate concentration of the instilled solution significantly decreased during a period of 30 min in both colonic segments, indicating absorption of succinate. The in vitro experiments revealed a distinct Na+ dependence of mucosal succinate uptake in all intestinal segments investigated. Because succinate uptake by the colonic mucosa of germ-free rats was similarly enhanced in the presence of Na+ compared with Na(+)-free conditions, measured uptake appears to be due to mucosal uptake rather than to Na(+)-dependent uptake of succinate by bacteria associated with the mucosa. The evaluation of the kinetics of succinate transport in the proximal colon and jejunum, respectively, revealed a single, Na(+)-dependent saturable component and a diffusive component in both intestinal segments. With respect to the apparent kinetic parameters of the carrier-mediated transport component, the transport capacity (Vmax) of the jejunal carrier appears to be substantially higher compared with the colonic mechanism (80 and 11 nmol cm-2 (5 min)-1, respectively) whereas the affinity constants (Km) did not differ markedly in both segments (0.67 and 0.41 mmol l-1, respectively). Mucosal uptake of 14C-labelled succinate in the proximal colon was inhibited by unlabelled succinate, fumarate, citrate and tricarballylate, but not by glutamate, L-leucine or butyrate. Na(+)-dependent uptake of the tricarboxylate tricarballylate but not of the dicarboxylate succinate was significantly enhanced by lowering the pH from 7.0 to 5.5, indicating preferential transport of the protonated forms of tricarboxylates. It is concluded from the present results that a Na(+)-dependent, saturable carrier is involved in the uptake of structurally related tri- and dicarboxylates by the colonic mucosa of the rat.

Studies of aloe. V. Mechanism of cathartic effect. (4).

Aloe-emodin-9-anthrone(AE-anthrone), produced from barbaloin in the rat large intestine, caused not only an increase in the intestinal water content but also stimulated mucus secretion. This might play an important role in the occurrence of diarrhea. It was demonstrated that the amount of AE-anthrone produced in the rat large intestine(maximal amount: 568 micrograms/rat at 4 h after injection) was enough to cause both of these effects, which were observed following intracecal administration of barbaloin (31.1 mg/kg). These results together with our previous data, which showed a relationship between increase in the intestinal water content and the stimulation of peristalsis, confirm that AE-anthrone is the principal agent responsible for the cathartic effect of barbaloin. We also propose that the increase in water content is a more important factor than stimulation of peristalsis in the induction of diarrhea by barbaloin.

Drug absorption from large intestine: physicochemical factors governing drug absorption.

Profiles of absorption versus drug molecular weight and absorption versus drug lipophilicity were investigated in both the small and large intestines of rats by an in situ loop method. The absorption-molecular weight profiles examined using different-sized polyethylene glycols (PEGs) were different between the small and large intestines; the large-intestinal absorption of PEGs with molecular weights larger than 300 was poor, while PEGs with molecular weights up to 600 were relatively well absorbed in the small intestine. It is suggested that the paracellular route for drug penetration in the large intestine is restricted more than in the small intestine. The absorption-lipophilicity profiles were also examined in various regions (loops of 6 cm) of rat intestine using three acylsalicylic acids, acetyl-, propionyl- and butyrylsalicylic acids. The absorption rates of the acylsalicylic acids were different in the intestinal regions: the jejunum > the ileum > the colon > the rectum. In each region, the absorption rate increased with the drug lipophilicity. However, it was shown that the absorption rates in the small intestine tended to reach a ceiling at the high lipophilicity. To confirm this tendency, the absorption rates of acetaminophen and indomethacin were compared in the four intestinal regions. The absorption rates of highly lipophilic indomethacin were similar in the large and small intestines, while intermediately lipophilic acetaminophen was more rapidly absorbed in the small intestine than in the large intestine. A thicker unstirred water layer adjacent to the small-intestinal mucosa would be one of the factors which cause such varying absorption-lipophilicity profiles.

Effect of Intestinal Resection on Phospholipid Class Distribution and Fatty Acid Composition of Mucosal Cells in the Rat Large Intestine

In this study we examined the effect of 50% distal small bowel resection (DSBR) on the lipid composition of rat colonic mucosa, including the fatty acid composition of major phospholipid classes, phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), lysophosphatidylcholine (LPC), and sphingomyelin (SM). Phospholipid, free cholesterol, triacylglycerols, diacylglycerols, and cholesterol ester levels were not affected by the surgical operation. PE together with PC accounted for more than 60% of total phospholipid, in both groups of animals. The relative percentages of PE, PC, PI, SM, and cardiolipin (CL) remained unaffected by DSBR. However, a decrease in the content of LPC was observed in 50%-resected animals. Different fatty acid composition changes in the colonic phospholipid classes were observed after resection. PC fraction contained the highest amounts of saturated fatty acids, but monounsaturated fatty acids were present in high levels in PI fraction, in both groups of animals. DSBR produces different changes in the levels of linoleic and arachidonic acids. These results suggest that the lipid composition and the fatty acid profile of the different phospholipid fractions change in the adaptive response of colon to intestinal resection.

Assessment of the Carcinogenic Potential of Chlorinated Water: Experimental Studies of Chlorine, Chloramine, and Trihalomethanes

Water chlorination has been one of the major disease prevention treatments of this century. While epidemiologic studies suggest an association between cancer in humans and consumption of chlorination byproducts in drinking water, these studies have not been adequate to draw definite conclusions about the carcinogenic potential of the individual byproducts. The purpose of this study was to investigate the carcinogenic potential of chlorinated or chloraminated drinking water and of four organic trihalomethane byproducts of chlorination (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) in rats and mice. Bromodichloromethane, chlorodibromomethane, bromoform, chlorine, or chloramine was administered to both sexes of F344/N rats and (C57BL/6 x C3H)F1 mice (hereafter called B6C3F1 mice). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3F1 mice. Chlorine or chloramine was administered daily in the drinking water for 2 years at doses ranging from 0.05 to 0.3 mmol/kg per day. The trihalomethanes were administered by gavage in corn oil at doses ranging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exception of chloroform, which was given for 78 weeks. The trihalomethanes were carcinogenic in the liver, kidney, and/or intestine of rodents. There was equivocal evidence for carcinogenicity in female rats that received chlorinated or chloraminated drinking water; this evidence was based on a marginal increase in the incidence of mononuclear cell leukemia. Rodents were generally exposed to lower doses of chlorine and chloramine than to the trihalomethanes, but the doses in these studies were the maximum that the animals would consume in the drinking water. The highest doses used in the chlorine and chloramine studies were equivalent to a daily gavage dose of bromodichloromethane that induced neoplasms of the large intestine in rats. In contrast to the results with the trihalomethanes, administration of chlorine or chloramine did not cause a clear carcinogenic response in rats or mice after long-term exposure. These results suggest that organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water.

Interoception and role of pain and discomfort from the small and large intestine in rats

The IZOF-based probabilistic approach provides a methodology to study within-individual patterns of a performer's states. So far, the time course of physiological data before performance have not been investigated within the probabilistic methodology framework. The purpose of this study was to examine the value of the probabilistic approach in the assessment of the time course of physiological indicators of arousal/activation and vigilance during the period preceding the shot, in comparison with the performance-based method.Longitudinal assessment of psycho-physiological data and performance outcomes was conducted on eight elite pistol shooters in a controlled setting.Each participant performed 60 air-pistol shots in 2 sessions. Skin conductance level and cardiac activity were recorded. Affective states intensity was evaluated on a modified 11-point Borg scale. Affect, HR and SC level were evaluated with a Performance-based approach and a Probabilistic method, and results compared at an individual level.Findings showed the higher effectiveness of the probabilistic method to analyse physiological parameters (skin conductance and heart rate) and to describe the physiological mechanisms associated with shooters’ performance.The probabilistic method better discerned the contribution of arousal/activation and vigilance to optimal and non-optimal performance in elite shooters, thereby providing a sharper representation of the temporal pattern of performers' states before shooting. From an applied perspective, we believe that the probabilistic approach can help athletes become aware of the subtle variations occurring in their psychophysical states during the preparatory period preceding the shot and not only at the moment of shot release.

Fiber fermentability in the rat cecum and its physiological consequences

The aim of the study was to compare the fermentability of complex fiber sources in the rat large intestine. The studied sources ranged from predominantly structural fiber (oat fiber and external pea fiber) to more soluble plant storage fibers (beet fiber and internal pea fiber) and were included at levels of about 13% or 26% TDF in the diet. Rats fed the diets containing the more insoluble fibers had a compensatory increase in intake, resulting in similar weight gains in all groups. Beet and internal pea fibers were better fermented, and caused a more pronounced hypertrophy of the cecum and greater absorption of short-chain fatty acids (SCFA). The SCFA profile varied with a higher proportion of butyrate in the cecal contents of rats fed the less soluble fibers and a higher proportion of propionate in those fed the internal pea fiber. Feeding fiber consistently enhanced the transfer of urea nitrogen into the cecum, enhancing fecal nitrogen excretion. The fiber diets elicited an accumulation of Ca and Mg in the cecum, the Ca and Mg absorption was closely correlated with the fermentability of the fibers. Except oat fiber, the studied fibers carried bile acids into the large intestine but also enhanced their cecal reabsorption. It appears that, besides analytical data on fiber solubility, the fermentability of complex fiber source is effectively appreciated by their effects on the parameters of cecal digestion.

Sites and patterns of absorption of 3,5,3'-triiodothyronine and thyroxine along rat small and large intestines.

It is clear that some thyroid hormone is absorbed from mammalian intestines, but numerous aspects of this process remain unresolved, including elucidation of the locations, extent and mechanisms of absorption, and the role of absorption in thyroid hormone economy. Our goal was to identify the sites and patterns and estimate rates of absorption of both tracer T4* and T3* comprehensively along the entire length of rat intestines, with normal contents included, to gain further insight into the role of this organ in whole-body thyroid hormone regulation. We measured absorption directly in situ in fed rats, using a variant of the classic intestinal loop technique used by others demonstrating absorption of T4 or of T3 from portions of rat intestines under various conditions. Rats were anesthetized, bile ducts were ligated, and absorption was measured from pylorus to anus, in 14 loops of intestines previously injected with T3* or with T4*, or with T3* and T4* injected in adjacent loops. Rats were maintained under otherwise approximately normal conditions, with intestines in situ and abdomen closed, until killing at 2 h. Excised loop radioactivity was measured and loops were homogenized, extracted, and chromatographed quantitatively to evaluate remaining and absorbed T3* and T4*. Absorption of both T3* and T4* were clearly present and were approximately uniform from all small and large intestinal sections, all containing normal intestinal contents, indicating that the entire organ is involved in whole-body thyroid hormone regulation. Furthermore, T3* and T4* were absorbed at approximately the same rate, adding to evidence reported by others for a simple diffusion absorption mechanism.

Studies on the microvascularization of the digestive tract by scanning electron microscopy of vascular corrosion casts. 1. Large intestine in rats and guinea pigs.

The colonic microvascularization of 10 adult Sprague-Dawley rats and guinea pigs (Cavia porcellus was studied by scanning electron microscopy of microvascular corrosion casts. The tunica muscularis is supplied by branches of the submucosal arteriolar plexus, according to the arrangement of muscle layers, longitudinally and transversally arranged capillaries are distinguished. The mucosal capillaries show a honeycomb pattern and mimic the openings of the mucosal glands. Parallel to the luminal aspect of the large intestine, the mucosal capillary loops often arise from the submucosal arterioles at the most abluminal aspect of the mucosa; however, some arterioles end just subjacent to these capillaries. The submucosal veins are located just subjacent to the capillaries of the lamina propria. The rat and guinea pig colonic vascular architecture revealed no differences, neither did the capillary density in different parts of the large intestine.

Three-dimensional ultrastructure of the autonomic nerve terminals in the lamina propria mucosae of the rat large intestine.

The three-dimensional ultrastructure of the autonomic nerve terminals in the lamina propria mucosae of the rat large intestine was studied by scanning electron microscopy using the KOH-collagenase digestion method as well as by transmission electron microscopy. Observations showed unmyelinated nerves in the lamina propria mucosae as well developed just above the muscularis mucosae and forming a two-dimensional irregular network by anastomosing with one another. Each nerve in the network consisted of axons and Schwann cells. The axons were about 0.1 micron in diameter and had local swellings (about 0.2-0.5 microns diameter) along their course. Transmission electron microscopy revealed the presence of synaptic vesicles in these varicosities. Although some of the axons left the Schwann cell processes to run separately, most of them twined around or were embedded in the Schwann cell bodies or processes. Blind ends of axons were only occasionally observed in the nerve network. These findings suggest that the network of the unmyelinated nerves itself represents a terminal apparatus acting upon the muscular and glandular cells.

Bacterially Synthesized Folate in Rat Large Intestine is Incorporated into Host Tissue Folyl Polyglutamates

Unlike mammalian tissues, certain intestinal microflora are capable of de novo synthesis of folate. To explore the availability of bacterially synthesized folate to the host organism, we used [3H] p-aminobenzoic acid (3H PABA) to label folate newly synthesized by the intestinal microflora. Labeled folates were isolated by affinity chromatography and identified by ion-pair HPLC. In this study [3H]PABA was injected into rat cecum to determine whether the [3H]folate synthesized by bacteria appeared in rat liver and other tissues. Rats were kept in sling suits to prevent coprophagy. Ion-pair chromatography of the purified liver folate demonstrated that bacterially derived [3H]folate was incorporated into all host liver-specific folate polyglutamates, mostly penta- and hexaglutamyl derivatives. Similar results were observed in kidney folates. These data provide direct evidence that some of the folate synthesized by the microflora in the rat large intestine is incorporated into the tissue folate of the host.

Rectal absorption of Zidovudine

Rectal absorption of Zidovudine (3′-azido-3′-deoxythymidine, AZT) was investigated in order to determine the feasibility of developing AZT suppositories. Although the small intestine shows a higher absorption rate than the stomach and large intestine in rats, considerable absorption of AZT was observed from the lower large intestine (8 cm above the anus). A sustained-release suppository was prepared by direct compression of hydroxypropyl cellulose (HPC) with AZT. During in vivo experiments in rats, this suppository (10 mg or 37.5 μmol AZT/kg) maintained constant plasma levels above 1 μM for more than 6 h. The results suggest that suppositories can prove useful as an alternative dosage form of AZT administration.

Lipid composition and peroxide levels of mucosal cells in the rat large intestine in relation to dietary fat

To examine whether dietary fat alters membrane lipid composition and peroxidation of polyunsaturated fatty acids in "non-proliferative" and "proliferative" cells in the large intestine, Sprague-Dawley rats were fed diets providing a polyunsaturated-to-saturated fatty acid ratio of 1.2 or 0.3 at a high or low level of fat intake for a 25-day period. Cell populations were isolated and the effect of dietary fat on membrane polyunsaturated fatty acid content and peroxide levels was determined. Neither fat level nor fatty acid composition of diet influenced total cholesterol, total phospholipids, and percentage of phospholipid classes in membrane phospholipids. Feeding the high fat and/or high polyunsaturated-to-saturated fatty acid ratio diet increased polyunsaturated fatty acid content of mucosal cell phospholipids. Increase in polyunsaturated fatty acid content was paralleled by a decrease in the monounsaturated fatty acid content of mucosal cell phospholipids. Membrane content of total saturated fatty acids was not significantly affected by diet. Variation in phospholipid fatty acid composition between "non-proliferative" and "proliferative" cells was observed. Lipid peroxide levels in mucosal cell lipid fractions were altered by dietary fat treatment. Animals fed high fat diets, compared to groups fed low fat diets, exhibited higher membrane peroxide levels when results are expressed as nmol/mg protein. Higher peroxide levels were observed in mucosal cells for rats fed high polyunsaturated-to-saturated fatty acid ratio diets when results were expressed per nmol of phospholipid. It is concluded that changes in fat level and fatty acid composition of the diet alters the mucosal cell membrane lipid composition in the rat large intestine and influences susceptibility of mucosal cell lipid to peroxidation. Further research is required to delineate which dietary factors--fat level, polyunsaturated-to-saturated fatty acid ratio, or both--have a primary influence on the degree of lipid peroxidation.