Inhibition of Prostaglandin Biosynthesis

Lands, William E.M.; Rome, Leonard H.

doi:10.1007/978-94-011-9648-2_3

Cited by 85 publications

(62 citation statements)

References 197 publications

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“…Evidence for a prostaglandin generating system at the hypothalamic level is that the precursor fatty acids cross the blood brain barrier (Alfin-Slater & Aftergood, 1968) and that hypothalamic centres concerned with regulation of food intake have been demonstrated to accumulate labelled linoleic acid when given intragastrically (Panksepp, 1975). Since paracetamol is a specific inhibitor of brain prostaglandin synthetase (Flower & Vane, 1972), the longer time lag in reversing anorectic activity of arachidonic acid shown in this study (Figure 1) (Lands, Letellier, Rome & Vanderhoek, 1973). Is there any pathological state where there is derangement of prostaglandin generating systems and resultant hyperphagia?…”

Section: Resultsmentioning

confidence: 80%

Anorectic Activity of Prostaglandin Precursors

Doggett

Jawaharlal

1977

British J Pharmacology

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1 Intraperitoneal and intragastric (i.g.) administration of prostaglandin precursors arachidonic (2 mg, 15 mg/kg, i.p.; 30 mg/kg, i.g.), linolenic (100 mg/kg, i.p.; 200 mg/kg, i.g.) and linoleic (15, 100 mg/kg, i.p.; 100 mg/kg, i.g.) acids to 22 h food‐deprived rats inhibits food intake. 2 This anorexia is similar to that induced by prostaglandin F2α (1 mg/kg, i.p.). 3 At anorectic doses these fatty acids do not cause pyrexia, in fact arachidonic acid causes hypothermia. 4 Prior treatment with indomethacin (15 mg/kg) and paracetamol (50 mg/kg) specifically reverses the anorexia and the behavioural satiety induced by the three fatty acids, while not affecting prostaglandin F2α‐induced suppression of food intake. 5 Results of the present experiments suggest that both physiological and pharmacological modification of appetite could be brought about through an effect on prostaglandin generating systems.

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Section: Resultsmentioning

confidence: 80%

Anorectic Activity of Prostaglandin Precursors

Doggett

Jawaharlal

1977

British J Pharmacology

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“…The observed 7.6% decrease in total PC (Table V) therefore supports the above hypothesis. It has been demonstrated that unsaturated fatty acids such as linoleic and oleic acid will both competitively and nonreversibly inhibit prostaglandin cyclooxygenase (18,19). If the phospholipase activities stimulated by thrombin were to release these fatty acids, the production of prostaglandins G2 and H2, and thromboxane A2 would be inhibited.…”

Section: Resultsmentioning

confidence: 99%

Selective release of archidonic acid from the phospholipids of human platelets in response to thrombin.

Bills¹,

Smith²,

Silver³

1977

J. Clin. Invest.

399

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“…During scavenging of free radicals it is converted to dehydroascorbic acid, DHA, in serum and in the mitochondrial fractions of various tissues [11]. It is also a co-factor in the biosynthesis and post-translational modification of collagen due to interaction with proline hydroxylase [12,13], and has been demonstrated to affect immune function [14], platelet activation [15], prostaglandin synthesis [16] and the polyol pathway [3]. These observations suggest apossible close interrelationship between AA metabolism and pathways known to be influenced by the diabetic process.…”

mentioning

confidence: 99%

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation

et al. 1991

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Summary. Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1+19.3 vs 55.6 _+ 20.0, p < 0.01, vs 82.9 _+ 30.9 gmol/1, p < 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87+0.46 vs 0.61 + 0.26, p < 0.01, vs 0.38 + 0.14, p < 0.001). At three weeks, ascorbate concentrations rose in all groups (p < 0.0001) and was maintained in control subjects (151.5 + 56.3 ~tmol/1), but fell in both diabetic groups by six weeks (p<0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p < 0.0001) but rose again in the diabetic groups by six weeks (p < 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p < 0.05). No significant changes were observed in fructosamine concentrations in any group during the study. Diabetes mellitus is associated with a major disturbance of ascorbic acid metabolism which is only partially corrected by ascorbate supplementation.Key words: Ascorbic acid, dehydroascorbic acid, diabetes mellitus, free radical activity, oxidative stress.Reduced levels and altered metabolic turnover of ascorbic acid (AA, vitamin C) have been reportedin severaltissues in experimen tally induced diabetes [1-3] and in diabeticpatients [4]. There are reports that high dose vitamin C regimens are associated with reversal of early signs of retinopathy [5] and normalisation of capillary strength in diabetes mellitus [6]. In the elderly non-diabetic population AA is often deficient and may be correctable by supplementation [7] -this problem might be of particular significance in elderly diabetic patients who are reported to show more rapid progress of some diabetic complications [8].Ascorbic acid functions as an important component of cellular defence against oxygen toxicity and lipid peroxidation caused by free radical mechanisms [9,10]. During scavenging of free radicals it is converted to dehydroascorbic acid, DHA, in serum and in the mitochondrial fractions of various tissues [11]. It is also a co-factor in the biosynthesis and post-translational modification of collagen...

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Inhibition of Prostaglandin Biosynthesis

Cited by 85 publications

References 197 publications

Anorectic Activity of Prostaglandin Precursors

Anorectic Activity of Prostaglandin Precursors

Selective release of archidonic acid from the phospholipids of human platelets in response to thrombin.

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation

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