Lead Pica Produced in Rats

Snowdon, Charles T.; Sanderson, Blythe A.

doi:10.1126/science.183.4120.92

Cited by 38 publications

(15 citation statements)

References 18 publications

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“…Consistent with the pattern of c-fos mRNA expression seen in the present study, cisplatin-induced vomiting in the ferret starts 2 h after administration and continues for 6 h (11). In rats, which show pica, a type of emesis (23,37), abdominal afferent vagal nerve activity increases 2 h after cisplatin treatment (13). Miller et al (25) clearly demonstrated that emetic drugs excite neurons in the AP.…”

Section: Discussionmentioning

confidence: 99%

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

et al. 2004

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Cancer chemotherapy-induced nausea and vomiting have been demonstrated to involve humoral as well as neuronal mechanisms. A leading role of serotonin (5-hydroxytryptamine, 5-HT) in these mechanisms is supported by inhibition of the emesis by 5-HT 3 receptor antagonists. We compared the effects of granisetron, a selective 5-HT 3 receptor antagonist, and vagotomy on c-fos mRNA expression in the nucleus of the solitary tract (NTS) and the area postrema (AP) of the rat caudal brainstem by means of in situ hybridization. The expression of c-fos mRNA in the NTS and AP was signifi cantly elevated 2 h after cisplatin administration. The induction of c-fos expression by cisplatin in the NTS was signifi cantly inhibited by pretreatment with granisetron. In contrast, the c-fos expression in the AP did not differ between the cisplatin group and the granisetron-treated cisplatin group. The degree of the induction of c-fos mRNA expression in both the AP and NTS was similar between the vagotomy and sham operation groups. Our results suggest that the expression of c-fos mRNA in the NTS may be specifi cally controlled by 5-HT 3 receptors and that nonspecifi c humoral factors, such as modulation of transcriptional activity, play an important role in c-fos expression in the AP after vagotomy.Neuronal sites and signal substances involved in cancer chemotherapy-induced nausea and vomiting have been identifi ed neurochemically (20). Serotonin type 3 receptor (5-HT 3 receptor) antagonists protect against emesis in experimental animal models as well as in cisplatin-treated patients with cancer (35). Autoradiographic studies of 5-HT in the central nervous system showed that binding sites with the strongest affi nity for 5-HT 3 receptors are located in the nucleus of the solitary tract (NTS) and the area postrema (AP) of the caudal brainstem (33).However, considerable evidence supports the hypothesis that cytotoxic drug-induced emesis is mediated by local 5-HT release in the intestinal wall (4,14,15,27,28). 5-HT has a potent depolarizing action on the vagal afferent nerve (18,34). It has been proposed that anticancer drugs cause 5-HT release from enterochromaffin (EC) cells to activate the 5-HT 3 receptors on the afferent vagal nerve fi bers (1,26). These afferent fi bers may project to the dorsal vagal complex, which also expresses 5-HT 3 receptors on its central terminals (20,33). The vomiting center receives input from the afferent vagal fi bers to evoke an emetic refl ex (1,20). The vagus is the major nerve involved in the detection of emetic stimuli, and the abdominal vagus contains approximately 80-90% of the afferent fi bers (3). Electrical

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Section: Discussionmentioning

confidence: 99%

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

et al. 2004

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“…This phenomenon may be mediated by inhibition of Na-KATPase activity [80], leading to a rise in vascular smooth muscle Na + content, which, in turn, enhances Ca 2+ influx. Interestingly, increased dietary calcium intake ameliorates lead-induced HTN, and a low-calcium diet increases the voluntary consumption of lead in rats [81], enhances the effect of lead on BP [82], and reduces lead clearance [83] Effect of lead on protein kinase C Protein kinase C (PKC) isoforms (a family of serinethreonine kinases) regulate numerous vascular functions, such as contractility, blood flow, vascular cell growth, and permeability. Exposure to lead has been shown to increase PKC activity in lead-exposed workers [84].…”

Section: Increased Vascular Tissue Calcium Content In Lead-induced Hymentioning

confidence: 99%

Lead-induced hypertension: Role of oxidative stress

Vaziri

Sica

2004

Current Science Inc

110

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Chronic, low-level lead exposure causes hypertension in both animals and humans. The pathogenesis of lead-induced hypertension is multifactorial, including such diverse mechanisms as: inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species (ROS), leading to a functional deficiency in nitric oxide; heightened sympathetic activity and plasma norepinephrine together with depressed vascular and elevated renal beta-adrenergic receptor density; elevated plasma angiotensin-converting enzyme (ACE) activity, plasma renin activity (PRA), angiotensin II (Ang-II), and aldosterone levels; increased kininase I and kininase II activities; lead-induced inhibition of vascular smooth muscle Na(+)-K+ ATPase, leading to a rise in cellular Na+ and, hence, Ca2+; and a possible rise in endothelin and thromboxane generation. In this article, we present an overview of the epidemiology and proposed underlying mechanisms of lead-induced hypertension.

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“…Biochemical mechanisms regulate calcium homeostatically and directly, but operate passively on related nonessential metals as a consequence of environmental trace occurences and, presumably, as a result of differences in chemical properties (Ericson et a!., 1979; Patterson, 1%5). Although lead is not a member of the calcium group in the periodic table, it shows similarities to barium and calcium and is partially regulated by calcium metabolism (Settle and Patterson, 1980;Snowden and Sanderson, 1974 Some research indicates that nonessential metals are discriminated against relative to related nutritious metals as the metals are transferred through biological systems. Alkaline earth metal concentrations were shown to increase in the order calcium > strontium > barium as the metals were transferred through food chains (Hardy et al, 1969).…”

Section: Introductionmentioning

confidence: 99%

Concentrations and Discrimination of Chemically Related Metals in a Food Chain

Lemons

Kennington

1983

Chemistry and Ecology

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Concentrations of the related elements calcium, strontium, barium, and lead were determined in soil extract, consumer stomach contents, and consumers in lead polluted and unpolluted areas. Discrimination against the nonessential metals relative to the nutritious metal calcium, as the metals were transferred through a trophic pathway was determined. Discrimination of metals varied systematically as a function of degree of nonessential element similarity to calcium. The existence of systematic trends of discrimination may facilitate the assessment of natural levels of some toxic elements (e.g. lead) in organisms.

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Lead Pica Produced in Rats

Cited by 38 publications

References 18 publications

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

Effects of granisetron and vagotomy on c-fos mRNA expression in the rat medulla oblongata as assessed by in situ hybridization

Lead-induced hypertension: Role of oxidative stress

Concentrations and Discrimination of Chemically Related Metals in a Food Chain

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