QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lim, S.-Y. Articles by Salem, N. Search for Related Content PubMed PubMed Citation Articles by Lim, S.-Y. Articles by Salem, N., Jr

---

Nutritional Neurosciences

Lead Exposure and (n-3) Fatty Acid Deficiency during Rat Neonatal Development Alter Liver, Plasma, and Brain Polyunsaturated Fatty Acid Composition¹

Sun-Young Lim, John D. Doherty^* and Norman Salem, Jr^,2

Division of Ocean Science, Korea Maritime University, Busan, Korea; ^* U.S. Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division, Washington, DC; and Laboratory of Membrane Biochemistry and Biophysics, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD

²To whom correspondence should be addressed. E-mail: nsalem{at}niaaa.nih.gov.

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Lead (Pb) exposure has been reported to increase arachidonic (AA) and docosahexaenoic (DHA) acids. To determine whether Pb effects on fatty acid composition are influenced by dietary (n-3) fatty acid restriction, weanling female rats were fed either an (n-3)-adequate or -deficient diet to maturity and mated. At parturition, dams in each group were subdivided to receive either 0.2% Pb or Na-acetate in their drinking water during lactation only. Pups were analyzed for fatty acid content in liver, plasma, and brain at either 3 or 11 wk. The (n-3)-deficient diets markedly decreased total (n-3) fatty acids, and increased total (n-6) fatty acids including both AA and docosapentaenoic (n-6) in each compartment (P < 0.05). The main effects of Pb were in the livers of weanling rats where there was a 56% loss in total fatty acid concentration concurrent with increased relative percentages of AA and DHA. Thus, because there was a greater percentage of liver nonessential fatty acid lost relative to the essential fatty acids (EFA), there was no net change in AA concentration. There was a diet x Pb interaction for a decrease in liver DHA concentration evident only in the (n-3)-adequate group. There were also diet x Pb interactions in plasma at 11 wk and in brain at 3 wk. These data are consistent with the hypothesis of a Pb-induced increase in fatty acid catabolism, perhaps as a source of energy.

KEY WORDS: • arachidonic acid • docosahexaenoic acid • fatty acid composition • lead • (n-3) fatty acid deficiency • Pb

Both lead (Pb) exposure (1) and a lower (n-3) intake (2) are developmental risks that frequently occur together in lower-income, urban populations. Thus, lower (n-3) fatty acid status may exacerbate adverse effects of Pb and, conversely, higher (n-3) status may serve to counteract some of the adverse effects of Pb on behavior. Pb is a ubiquitous environmental contaminant that causes a variety of toxicological responses in laboratory animals and humans (3,4), including deficits in behavioral tasks (5,6). The effects of Pb appear to be greater when exposure is in utero or during lactation (7,8). Pb exposure also leads to changes in fatty acid composition; it was proposed that this is due to a Pb-induced increase in lipid peroxidation (9–11). Although a specific molecular mechanism for Pb toxicity is unclear, targets such as ion channels, neurotransmitter systems, and signaling molecules have been invoked (12). A deficit in (n-3) fatty acid intake during the fetal or early postnatal period leads to a loss of brain docosahexaenoic acid (DHA)³ and suboptimal nervous system development as reflected by poorer performance in a variety of behavioral tasks (13–15). DHA also exerts its effects through a variety of mechanisms including several proposed for the effect of Pb, i.e., ion channels (16), neurotransmitter systems (17), and signal transduction systems (18). Therefore, Pb and DHA deficiency may exert similar effects on similar biochemical systems; their effects may be additive and possibly exerted through alteration of DHA or other PUFA. This study was thus designed to define the effects of both (n-3) fatty acid deficiency and Pb exposure on the fatty acid composition of the nervous system and peripheral tissues involved in fatty acid synthesis (liver) and transport (plasma). Rat pups were exposed to an (n-3)-adequate [(n-3) Adq] or an (n-3)-deficient [(n-3) Def] diet through fetal development and lactation and were then exposed to Pb throughout lactation. Tissue fatty acid composition was studied at the end of Pb exposure, at weaning, or in adulthood 8 wk after Pb exposure had ceased.

	MATERIALS AND METHODS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Animals and study design. A complete description of the animal procedures is contained in an accompanying paper (19). Briefly, dams were fed an (n-3) Def or (n-3) Adq diet during gestation and their pups were subdivided into 2 groups and placed with dams given drinking water containing either 0.2% (or 5.27 mmol/L) lead acetate or a 0.2% solution of sodium acetate. The 4 groups were designated as (n-3) Adq-Na, (n-3) Adq-Pb, (n-3) Def-Na and (n-3) Def-Pb to identify their diet and treatment with either Pb or Na. The rat pups were kept with their dams until weaning at 21 d. At weaning, 1 male pup was taken from each of the dams from each of the 4 experimental groups (4 groups x 5 pups/group = 20 pups) and decapitated. Separate groups of male pups were fed the respective diets of their dams (n = 10/group) but Pb exposure was discontinued after weaning. These rats were used for behavioral experiments (19) and then analyzed at 11 wk for tissue fatty acid composition as described below. Lead concentration was measured in whole blood using atomic absorption spectrometry at a commercial laboratory (Antech Diagnostics).

    Experimental diet. The (n-3) Adq and (n-3) Def diets are detailed in a previous publication (20). They were based on the AIN-93 formulation (21) with the critical difference that -linolenate (LNA) and DHA were added to the (n-3) Adq diet. The total fat content in both diets was 10% and the amount of LNA in the (n-3) Def and (n-3) Adq diets was 0.09 and 3.0% of total fatty acids, respectively, with the (n-3) Adq diet containing 1.45% DHA.

    Lipid composition. At 3 and 11 wk of age, rats were decapitated and their brains and livers were weighed and quickly frozen (–80°C) for subsequent analyses for lipid composition. Blood was collected into centrifuge tubes and immediately centrifuged at 1000 x g at 4°C; the plasma was removed for analysis. Lipid extraction (22), fatty acid transmethylation (23), and GC analysis (24) of fatty acid profiles were performed as previously described.

    Statistical analysis. All data are expressed as the means ± SEM; significance was determined by 2-way ANOVA with interactions for diet and Pb exposure effects using Statistica (Statsoft) for body and tissue weight. When the F-test was significant (P < 0.05), comparisons among groups were performed using Tukey’s Honestly Significant Difference test. For tissue fatty acids, multivariate comparison analysis was performed using SPSS to reduce the risk of slippage with multiple dependent variable testing. Comparisons were made between diet and Pb groups at each of the 2 time points. Homoscedasticity of variances was examined using Levene’s test of equality of error variances function in SPSS. For variables with heteroscedastic variances, the individual data points were rank transformed and the analyses were repeated. The statistical findings after rank transformation analyses did not alter the conclusions of the primary analysis. Differences were considered significant at P < 0.05.

	RESULTS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Clinical signs, body, liver, and brain weights. Lead affected body and liver weights for rats at both 3 and 11 wk of age but did not affect brain weight (Table 1). At weaning (3 wk), the pups from dams fed either the (n-3) Adq-Pb or (n-3) Def-Pb diet were 50% smaller based on body weight (P < 0.001) or liver weight (P < 0.001) compared with the corresponding pups in the Na groups. The body and liver weight differences between Pb and Na acetate groups continued throughout growth. At 11 wk of age, rats from the dams administered Pb had lower body weights (23–26%, P < 0.001) and liver weights (25–28%, P < 0.001) than the Na groups. There was no diet effect on any of these weight variables.

    Fatty acid compositions: effects of diet. The total fatty acid concentrations of the liver, plasma, or brain did not differ between the (n-3) Def and the (n-3) Adq groups at both ages studied (3 and 11 wk). As expected, in the (n-3) Def compared with the (n-3) Adq groups, the concentrations of total and many individual (n-3) fatty acids were reduced in all 3 tissues studied for both Pb- and Na-supplemented rats at 3 and 11 wk (Tables 2, 3, 4, 5, 6, 7). In the (n-3) Def groups, the concentration of total (n-3) fatty acid in the livers (Tables 2, and 3) was much lower (94%) than in the (n-3) Adq groups and plasma (93% at both 3 wk and 11 wk, Tables 4, and 5). The brain also had a much lower concentration of total (n-3) fatty acid in the (n-3) Def groups (86% lower after 3 wk and 79% lower after 11 wk, Tables 6, and 7). Most of the decreased concentrations of total (n-3) fatty acids could be accounted for by a markedly lower concentration of DHA; in brain, the DHA accounted for 97% of the loss in (n-3) content (Tables 6, and 7). In brain, the 22:5(n-3) concentration was also much lower although this was a relatively minor component. In plasma (Tables 4, and 5) and liver, 18:3(n-3), 20:5(n-3), 22:5(n-3), and DHA were all at markedly lower concentrations in the (n-3) Def group.

    Pb effects on liver fatty acid composition. The effects of Pb on fatty acid composition were most pronounced in the liver of 3-wk-old pups (Table 2) where Pb exposure resulted in decreased concentrations of total SFA [63% decline in (n-3) Adq and 41% decline in the (n-3) Def group] and total MUFA [73% decline in the (n-3) Adq and 51% decline in the (n-3) Def group]. Decreased total MUFA in the liver after Pb exposure was due mainly to decreased concentrations of 18:1(n-9) and 18:1(n-7). The significant decline in SFA after Pb exposure was accounted for mainly by decreases in 14:0 and 16:0. The concentration of total fatty acids was significantly decreased by 59% in the livers of the (n-3) Adq-Pb group compared with the (n-3) Adq-Na group after 3 wk. In the (n-3) Def groups, Pb exposure led to a 32% loss in total fatty acid concentration.

There were Pb x Diet interactions for several (n-6) and (n-3) fatty acids in the liver at 3 wk with greater losses in EFA associated with Pb exposure in the (n-3) Adq group. There were significant interactions of Pb x Diet for LA, 20:2(n-6), DPA (n-6), LNA and DHA.

Many of the same effects, albeit somewhat lessened, were observed in the 11-wk-old rats, even though Pb exposure had ceased after the time of weaning at 3 wk. There were no significant effects of Pb on the total fatty acid concentration or on total (n-3) or (n-6) polyunsaturates (Table 3). However, total SFA and MUFA were significantly decreased with Pb exposure.

    Pb effects on plasma fatty acid composition. There were no main effects of Pb on the plasma total fatty acid concentration nor on the total SFA, total MUFA, total (n-6), or total (n-3) fatty acids in plasma at 3 wk (Table 4). There was no effect of Pb exposure on plasma total MUFA concentration after 11 wk (Table 5). However, at 11 wk, there was a diet x Pb exposure interaction for total SFA, total (n-6), and (n-3) PUFA, and total fatty acid concentration because there was a much greater effect of Pb on the (n-3) Adq group (P < 0.05). There were significant Pb x Diet interactions for all of the plasma (n-3) fatty acids at 11 wk as well as for LA, 20:3(n-6), 22:4(n-6), and DPA (n-6).

    Pb effects on brain fatty acid composition. There were no main effects of Pb exposure on total fatty acid concentration, total SFA, total MUFA, total (n-6), or total (n-3) fatty acids in either the 3- (Table 6) or 11-wk-old (Table 7) rats. However, there was a diet x Pb exposure interaction for 22:5(n-3) in the 3-wk-old pup groups. The (n-6) fatty acid species, LA and 20:3(n-6), were decreased by Pb (26 and 29%, respectively) in the 3-wk-old (n-3) Adq groups; however, these are relatively minor components of brain.

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Increased percentages of AA were observed in Pb-exposed rats (25), chickens (11,26–28), and humans (29). Donaldson and Leeming (26) observed that in chicks fed a diet containing various levels of lead for the first 21 d of life, the percentage of liver AA was not increased with diets containing 2.41, 3.62, 4.83 mmol Pb/L, but only when the Pb level was 9.65 mmol/L. In an expansion of this work, Lawton and Donaldson (11) observed a dose-response relation between the percentage of AA and the Pb concentration (range 0.30–4.83 mmol/L) in several measures including chick liver total lipids, liver phospholipids, liver mitochondria and microsomes, and serum lipids. Zimmerman et al. (25) reported increases in the percentages of erythrocyte AA and DHA after in utero and 4 mo of postnatal exposure to 0.4% lead acetate in their drinking water. Knowles et al. (28) subsequently reported increased percentages of AA and DHA in rats, turkeys, and children. More recently, Osterode and Ulberth (29) reported an increased percentage of AA and 22:4(n-6) and a correlation between blood Pb and the percentage of AA, but no increase in DHA in chronically lead-exposed men.

In every case, the measurement performed was the fatty acid expressed as the percentage of total fatty acid weight; however, many of the above authors claimed increased AA concentration (11,26–29). Our results do indeed indicate that there is indeed a significant increase in the percentage of liver AA during high-level (5.26 mmol/L) Pb exposure. When analyzed as a percentage, our results indicate a significant elevation in rat liver at both 3 and 11 wk and for both the (n-3) Adq and (n-3) Def diets. Many of these increases were very sizeable; for example, liver AA increased from 4.5% in the (n-3) Adq-Na control to 11% in the (n-3) Adq-Pb groups, a more than doubling of the percentage. A similar situation exists for liver DHA because Pb exposure led to increased percentages. However, there was no significant increase in the concentration of liver AA or DHA due to Pb exposure at either time point or in either diet. This may appear incongruous, but it must be understood that Pb exposure leads to a loss in total fatty acids and the ones lost are preferentially composed of SFA and MUFA. Thus, the sparing effect of EFA raises the percentages of these components while having no effect on their tissue concentration. Unfortunately, several authors have referred to their percentage data in terms of concentration (11,23–26), an extrapolation that is unwarranted by their data and is herein shown to be incorrect.

There was then a selective loss of liver nonessential fatty acids with respect to the (n-3) and (n-6) EFA and a similar trend in other tissues studied. It appeared that there was also selectivity with respect to the chain length of fatty acids to be lost with fatty acids of >18C lost as a lower rate than those 18C.

In this study, possible interactions of (n-3) fatty acids in the diet and Pb exposure were examined. Some interactions were observed for Diet x Pb exposure in the statistical analysis of the liver (at 3 wk) and plasma (at 11 wk). Generally, this interaction occurred because there was a greater effect of Pb on the (n-3) Adq groups, in which Pb exposure decreased fatty acid concentrations, than was observed for the (n-3) Def groups, in which little change or increases were observed. One example is DHA in the 3-wk-old liver where Pb exposure led to a 38% decrease in the (n-3) Adq group but a 52% increase in the (n-3) Def group and where total (n-3) fatty acids exhibited a similar behavior. A "floor effect" may be responsible in part for this behavior because (n-3) fatty acid levels are very low in liver and plasma for (n-3) Def rats. However, interactions are also observed for the (n-6) fatty acids where the concentrations are substantial and a floor effect does not provide an adequate explanation. A relevant observation is that all of the diets contained a constant and a high level of (n-6) fatty acids because they contain 15% LA, which may better support (n-6) fatty acid tissue content during Pb exposure.

Little is understood about the manner in which Pb exposure may alter lipid metabolism. There have been several suggestions that Pb induces lipid peroxidation. Chicks given 7.24 mmol Pb/L had increased liver malondialdehyde at 2 of the 5 time points measured (11). In a similar assay for erythrocytes, there was no difference in basal status after Pb exposure, but only when the rats were injected with Triton detergent (25). After chicks were exposed for 16 d to 7.24 mmol Pb/L, more malondialdehyde was produced in their microsomal membranes in vitro (27). These observations led to the proposal that many of the biological reflects of Pb are related to tissue peroxidation.

It is likely that increased peroxidation would lead to decreased tissue concentrations of AA, DHA, and other highly unsaturated fatty acids. In fact, peroxidation would be expected to preferentially affect PUFA rather than SFA and MUFA. This is inconsistent with the frequent reports of an increased percentage of AA and DHA in the literature, and the preferential loss of nonessential fatty acids in Pb-exposed rats described in this study. The largest absolute change in fatty acid content occurred at 3 wk in the liver in the (n-3) Adq group for which the largest loss occurred in total SFA (a loss of 69.4 nmol/mg wet weight). Thus, the peroxidation mechanism for Pb action would be an unlikely candidate to explain the fatty acid profiles observed here. Alternatively, it may be hypothesized that Pb inhibits fatty acid desaturases. In this case, unsaturated fatty acids would be lost in preference to SFA. This profile is inconsistent with the one observed in the Pb-exposed rat liver and is thus unlikely.

We propose that the nonessential fatty acids were being preferentially degraded for energy in the Pb-exposed rats, although it is clear that liver EFA were also being lost. This is consistent with their lower body weight and lower liver weight, indications of decreased energy intake. When Pb exposure was discontinued and the rats were allowed to recover, the differences between the Pb-exposed and unexposed groups in body and liver weights diminished with time, and the fatty acid compositional changes also diminished or were absent. After 11 wk, the (n-3) and (n-6) PUFA had fully recovered, but differences in nonessential fatty acids persisted.

	FOOTNOTES

 
¹ Supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.

³ Abbreviations used: AA, arachidonic acid, 20:4(n-6); DHA, docosahexaenoic acid, 22:6(n-3); DPA (n-6), docosapentaenoic acid (n-6), 22:5(n-6); EFA, essential fatty acid; LA, linoleic acid, 18:2(n-6); LNA, -linolenic acid, 18:3(n-3); MUFA, monounsaturated fatty acids; (n-3) Adq-Na, (n-3) adequate and Na control group; (n-3) Adq-Pb, (n-3) adequate and Pb exposure group; (n-3) Def-Na, (n-3) deficient and Na control group; (n-3) Def-Pb, (n-3) deficient and Pb exposure group.

Manuscript received 30 March 2004. Initial review completed 15 June 2004. Revision accepted 17 February 2005.

	LITERATURE CITED

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

1. Bernard, S. M. & McGeehin, M. A. (2003) Prevalence of blood lead levels 5 µg/dL among US children 1 to 5 years of age and socioeconomic and demographic factors associated with blood of lead levels 5 to 10 µg/dL, Third National Health and Nutrition Examination Survey, 1988–1994. Pediatrics 112:1308-1313.[Abstract/Free Full Text]

2. Lewis, N. M., Widga, A. C., Buck, J. S. & Frederick, A. M. (1995) Survey of omega-3 fatty acids in diets of Midwest low-income pregnant women. J. Agromed. 2:49-57.

3. Goyer, R. A. (1996) Results of lead research: prenatal exposure and neurological consequences. Environ. Health Perspect. 104:1050-1054.[Medline]

4. Cory-Slechta, D. A. (1986) Prolonged lead exposure and fixed ratio performance. Neurobehav. Toxicol. Teratol. 8:237-244.[Medline]

5. Cory-Slechta, D. A. & Schaumberg, H. A. (2000) Inorganic lead. Spencer, P. S. Schaumberg, H. A. eds. Experimental and Clinical Neurotoxicology 2000:708-719 Oxford University Press New York, NY .

6. Rice, D. C. (1996) Behavioral effects of lead: commonalities between experimental and epidemiologic data. Environ. Health Perspect. 104(suppl. 2):337-351.

7. Kuhlmann, A. C., McGlothan, J. L. & Guilarte, T. R. (1997) Developmental lead exposure causes spatial learning deficits in adult rats. Neurosci. Lett. 233:101-104.[Medline]

8. Murphy, K. J. & Regan, C. M. (1999) Low-level lead exposure in the early postnatal period results in persisting neuroplastic deficits associated with memory consolidation. J. Neurochem. 72:2099-2104.[Medline]

9. Donaldson, W. E. & Knowles, S. O. (1993) Is lead toxicosis a reflection of altered fatty acid composition of membranes?. Comp. Biochem. Physiol C 104:377-379.

10. Yiin, S. J. & Lin, T. H. (1995) Lead-catalyzed peroxidation of essential unsaturated fatty acid. Biol. Trace Elem. Res. 50:167-172.[Medline]

11. Lawton, L. J. & Donaldson, W. E. (1991) Lead-induced tissue fatty acid alterations and lipid peroxidation. Biol. Trace Elem. Res. 28:83-97.[Medline]

12. Banks, E. C., Ferretti, L. E. & Shucard, D. W. (1997) Effects of low level lead exposure on cognitive function in children: a review of behavioral, neuropsychological and biological evidence. Neurotoxicology 18:237-281.[Medline]

13. Okuyama, H., Kobayashi, T. & Watanabe, S. (1996) Dietary fatty acids–the n-6/n-3 balance and chronic elderly diseases. Excess linoleic acid and relative n-3 deficiency syndrome seen in Japan. Prog. Lipid Res 35:409-457.[Medline]

14. Salem, N., Jr, Litman, B., Kim, H. Y. & Gawrisch, K. (2001) Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 36:945-959.[Medline]

15. Uauy, R., Hoffman, D. R., Mena, P., Llanos, A. & Birch, E. E. (2003) Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials. J. Pediatr. 143:S17-S25.[Medline]

16. Kang, J. X. & Leaf, A. (1996) Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins. Proc. Natl. Acad. Sci. U.S.A. 93:3542-3546.[Abstract/Free Full Text]

17. Chalon, S., Vancassel, S., Zimmer, L., Guilloteau, D. & Durand, G. (2001) Polyunsaturated fatty acids and cerebral function: focus on monoaminergic neurotransmission. Lipids 36:937-944.[Medline]

18. Niu, S. L., Mitchell, D. C., Lim, S. Y., Wen, Z. M., Kim, H. Y., Salem, N., Jr & Litman, B. J. (2004) Reduced G protein-coupled signaling efficiency in retinal rod outer segments in response to n-3 fatty acid deficiency. J. Biol. Chem. 279:31098-31104.[Abstract/Free Full Text]

19. Lim, S.-Y., Doherty, J., McBride, K., Miller-Ihli, N., Carmona, G., Stark, K. & Salem, N., Jr (2005) Lead exposure and (n-3) fatty acid deficiency during neonatal development affect subsequent spatial task performance and olfactory discrimination. J. Nutr. 135:1019-1026.[Abstract/Free Full Text]

20. Moriguchi, T., Greiner, R. S. & Salem, N., Jr (2000) Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J. Neurochem. 75:2563-2573.[Medline]

21. Reeves, P. G., Nielsen, F. H. & Fahey, G. C., Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J. Nutr. 123:1939-1951.

22. Folch, J., Lees, M. & Sloane-Stanley, G. H. (1957) A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226:497-509.[Free Full Text]

23. Morrison, W. R. & Smith, L. M. (1964) Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J. Lipid Res. 5:600-608.[Abstract]

24. Salem, N., Jr, Reyzer, M. & Karanian, J. (1996) Losses of arachidonic acid in rat liver after alcohol inhalation. Lipids 31(suppl.):S153-S156.

25. Zimmermann, L., Pages, N., Antebi, H., Hafi, A., Boudene, C. & Alcindor, L. G. (1993) Lead effect on the oxidation resistance of erythrocyte membrane in rat triton-induced hyperlipidemia. Biol. Trace Elem. Res. 38:311-318.[Medline]

26. Donaldson, W. E. & Leeming, T. K. (1984) Dietary lead: effects on hepatic fatty acid composition in chicks. Toxicol. Appl. Pharmacol. 73:119-123.[Medline]

27. Knowles, S. O. & Donaldson, W. E. (1996) Dietary lead alters fatty acid composition and membrane peroxidation in chick liver microsomes. Poult. Sci. 75:1498-1500.[Medline]

28. Knowles, S. O., Donaldson, W. E. & Andrews, J. E. (1998) Changes in fatty acid composition of lipids from birds, rodents, and preschool children exposed to lead. Biol. Trace Elem. Res. 61:113-125.[Medline]

29. Osterode, W. & Ulberth, F. (2000) Increased concentration of arachidonic acid in erythrocyte membranes in chronically lead-exposed men. J. Toxicol. Environ. Health A 59:87-95.[Medline]

This article has been cited by other articles:

				C.-W. Chen and H.-H. Cheng A Rice Bran Oil Diet Increases LDL-Receptor and HMG-CoA Reductase mRNA Expressions and Insulin Sensitivity in Rats with Streptozotocin/Nicotinamide-Induced Type 2 Diabetes J. Nutr., June 1, 2006; 136(6): 1472 - 1476. [Abstract] [Full Text] [PDF]

				S.-Y. Lim, J. D. Doherty, K. McBride, N. J. Miller-Ihli, G. N. Carmona, K. D. Stark, and N. Salem Jr Lead Exposure and (n-3) Fatty Acid Deficiency during Rat Neonatal Development Affect Subsequent Spatial Task Performance and Olfactory Discrimination J. Nutr., May 1, 2005; 135(5): 1019 - 1026. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lim, S.-Y. Articles by Salem, N. Search for Related Content PubMed PubMed Citation Articles by Lim, S.-Y. Articles by Salem, N., Jr