Lois S. Gallon

Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats

Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid content, were fed to partially nephrectomized rats; the effects were compared to those of feeding beef tallow. All three oils had favorable effects on progression of renal failure, salmon oil on kidney histology as well. The changes induced in platelet production of thromboxane A2, and in the renal production of various eicosanoids may explain the protective role of these oils.

Protective effect of polyunsaturated fatty acid supplementation in apoferritin induced murine glomerulonephritis.

The effects of increasing two dietary polyunsaturated fatty acids, eicosapentaenoic and linoleic, on the glomerulonephritis induced by repeated injections of apoferritin in the mouse were studied. Urinary protein excretion was measured serially; serum creatinine, aortic and renal production of eicosanoids and kidney histology were measured at sacrifice at 8 weeks. Both high EPA and LA feedings were associated with lesser proteinuria, normalization of renal function and profound changes in the tissue production of prostaglandin and thromboxane, which may explain their protective effect in this model of renal disease.

Measurement of prostaglandin E3 and other eicosanoids in biologic samples using high pressure liquid chromatography and radioimmunoassay.

A method to measure PGE3 in biologic samples is described. Complete resolution of PGE3 from PGE1 and PGE2 is achieved by reversephase high pressure liquid chromatography. Quantification is carried out by radioimmunoassay using an antibody directed against PGE2 that has high cross-reactivity with PGE3. Using this method, a marked increase in PGE3 production by mouse kidney tissue and in rat urine was demonstrated after supplemental feeding of omega-3 fatty acids. This method can also be applied to measurement of 6-keto-PGF1 alpha and TXB2 in the same samples.

Persistent enhancement of bile acid synthesis in guinea pigs following stimulation of cholesterol catabolism in neonatal life.

Cholesterol catabolism to bile acids was stimulated in neonatal guinea pigs by feeding 1.11% cholestyramine (CT)-containing diet for 8 weeks. The animals were then switched to standard laboratory diet for an additional 4 weeks. At the end of the laboratory diet period: a) CT-pre-treated guinea pigs continued to excrete significantly higher (p less than 0.05) amounts of bile acids, b) the activity of hepatic 7 alpha-hydroxylase was significantly elevated (p less than 0.01) in CT-pre-treated animals, and c) isolated hepatocytes from CT-pre-treated guinea pigs secreted significantly higher (p less than 0.05) amounts of bile acid when compared to controls during a 4-hour incubation. These data provide biochemical support for our contention that stimulation of cholesterol catabolism during neonatal life can have effects that persist into adult life.

Effect of Specific Estrogens on Prostaglandin Synthesis in Aorta and Thrombocytes of Female Pigeons

Abstract The effect of two major natural estrogens (estrone and 17β-estradiol) on prostaglandin biosynthesis from [14C]arachidonic acid in thrombocytes and aorta of female pigeons was compared with that of a male sex hormone (testosterone). In the aorta, 17β-estradiol stimulated the synthesis of 6-keto PGF1α and PGF2α but markedly reduced the synthesis of PGE2. Estrone on the other hand stimulated the synthesis of PGE2. Testosterone stimulated the synthesis of all prostaglandins in the aorta. In the thrombocytes, 17β-estradiol decreased aggregatory response to arachidonic acid and synthesis of thromboxane B2. Estrone on the other hand increased aggregatory response to arachidonic acid. Testosterone decreased the synthesis of thromboxane B2. These studies have documented markedly different effects of estrone and 17β-estradiol on prostaglandin metabolism in aorta and thrombocytes of female pigeons. Furthermore, it is suggested that testosterone when administered to female pigeons might cause favorable effects through decrease in (a) plasma lipid levels and (b) the synthesis of thromboxane B2 in thrombocytes.

Enhancement of Thrombocyte Aggregation and Thromboxane B2 Synthesis by Diethylstilbestrol

Effect of diethylstilbestrol administration on thrombocyte aggregation and thromboxane B2 synthesis was investigated in atherosclerosis-susceptible pigeons. Platelet aggregatory response to arachidonic acid and synthesis of thromboxane B2 from 14C-arachidonic acid was enhanced in thrombocytes derived from diethylstilbestrol-treated pigeons. Platelet total phospholipid concentration was increased in pigeons with diethylstilbestrol treatment. Enhanced thromboxane synthesis might be responsible for increased platelet aggregation, which in turn might contribute to the severe atherosclerosis noted following diethylstilbestrol treatment in several avian species.

Renal prostaglandin production is increased during abdominal sepsis in the rat and unaffected by the infusion of different amino acid formulations

Renal prostaglandin (PG) production was studied in 32 laparotomized (control) and 33 septic rats (cecal ligation and puncture). Control and septic rats were infused for 18 hr with 5% glucose or 5% glucose and one of three amino acid formulations containing 22, 35, or 45% branched chain amino acids. When comparing renal PG production from endogenous precursors in septic versus control rats, significant increases (P less than 0.01) could be detected for PGE2, 6-keto-PGF1 alpha, and TxB2. The infusion of either 5% glucose alone or 5% glucose with 4.25% of any of the three amino acid formulations tested did not change renal PG production in either control or septic rats.

Prostaglandins in the Bronchoalveolar Lavage Fluid

Prostaglandins are naturally occurring substances that act as local, potent hormones.‘ The lung is one of the major sites for prostaglandin synthesis and degradation. Various stimuli cause the release of prostaglandins from the lung, but the role of these released substances is only beginning to unfold. Prostaglandins are involved in many physiological events. Traditionally, prostaglandins have been characterized as a major cause of the initiation and perpetuation of inflammatory responses. Recently, some classes of prostaglandins have been shown to have anti-inflammatory properties. This is particularly true for prostaglandin of the E class (PGE). PGE has been shown to be immunoregulatory, acting as a feedback inhibitor of T cell aggregation and an inhibitor of macrophage cytotoxicity? For example, increased activity of PGE-producing cells in the peripheral blood has been shown to be a contributing cause of anergy in some patients with sarcoidosis? The role of PGE in granuloma formation is beginning to be understood. PGE is decreased in concentration in granulomas? The exogenous administration of PGE inhibits the induction and elicitation phase of the cell-mediated response of Schistosoma mansoni egg-induced pulmonary granuloma^.^ Bronchoalveolar lavage (BAL) is a widely used technique for sampling lung fluid in the distal airways. Recently, we described a technique that allowed us to quantitate the volume of lung fluid retrieved and to thus report lavage results per ml of lung fluid.6 We measured the amounts of PGE in normal volunteers and patients with active pulmonary sarcoidosis.