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PubMed1986

Release of endotoxin from bacteria exposed to ciprofloxacin and its prevention with polymyxin B.

An in vitro system for studying the phenomenon of antibiotic-induced release of endotoxin from gram-negative bacteria is described. Endotoxin was measured by a quantitative limulus lysate microassay. Using a strain of Escherichia coli, ciprofloxacin was shown to cause an immediate and sustained increase in endotoxin release compared to control cultures whereas gentamicin did not, despite an equally rapid bactericidal effect. The potential value of the anti-endotoxin effect of polymyxin B was examined using a polymyxin B resistant strain of Klebsiella aerogenes. Ciprofloxacin alone caused endotoxin release, but when given with polymyxin B significantly less endotoxin was detected. These results indicate that in antibiotic-induced endotoxin release, the rate of cell death is less important than the site of antibiotic effect, and suggest that ciprofloxacin may act directly on the cell wall as well as on DNA gyrase. It is possible that polymyxin B could be used to reduce the extent of endotoxin release, and that this would be of clinical benefit.

Cell Wall↗
PubMed1996

IL-1 is an important mediator for microcirculatory changes in endotoxin-induced intestinal mucosal damage.

Although small intestine is frequently injured in endotoxin shock, the exact pathological sequence has not been fully understood. The major objective of this study is to elucidate the role of interleukin (IL)-1 in endotoxin-induced microcirculatory disturbance of rat small intestine. Mucosal and submucosal microvessels of the rat ileum were observed by intravital microscope with a high speed video camera system and the attenuating effect of E5090, an inhibitor of IL-1 generation, on endotoxin-induced intestinal microcirculatory disturbances was investigated. Endotoxin infusion produced significant mucosal damage, but before these morphological changes became significant, microvascular stasis in villi, decreased red blood cell velocity, and increased leukocyte adherence to venular walls were observed in intestinal microcirculatory beds 30 min after endotoxin administration. Intestinal IL-1alpha levels were also significantly increased at that time. Endotoxin treatment enhanced chemiluminescence activity from neurophils and rapidly mobilized CD18 on leukocytes. E5090, which suppressed the IL-1 production in intestinal mucosa, attenuated the microcirculatory disturbances induced by endotoxin, and significantly reduced the subsequent mucosal damage. E5090 also attenuated the increased chemiluminescence activity and CD18 expression on leukocytes. In conclusion, the production of IL-1alpha is enhanced in the intestinal mucosa during endotoxin infusion. IL-1 may be an important mediator of microcirculatory changes, including decreased red blood cell velocity and increased leukocyte sticking and its activation, leading to the mucosal damage.

Acrylates↗
PubMed1999

Acute effects of vitamin A on the kinetics of endotoxin in conscious rabbits.

BACKGROUND: Vitamin A reduces the pathophysiological effects of endotoxin in animals, but the mechanism and the lowest effective dose are not clear. METHODS: An intravenous bolus of endotoxin 20 microg. kg(-1) was given to 30 rabbits. In 10 of them, 1000 IE. kg(-1) retinyl palmitate was injected intravenously 1 h before the endotoxin and in another 10 rabbits 1 h after the endotoxin. A one-compartment open model was fitted to the time-concentration profile of endotoxin in plasma. RESULTS: The half-life of endotoxin was half as long when vitamin A was given for prophylaxis (median 35 min) and for treatment (33 min) than in the controls (67 min; p < 0.004). The plasma concentrations of immunoglobulin G and M endotoxin-core antibodies, the leucocyte count and the acid-base balance did not differ between the groups during the experiment, but the pyrogenic reaction was more pronounced in the controls. CONCLUSION: A fairly low dose of vitamin A reduced the half-life of endotoxin.

Analysis of Variance↗
PubMed2001

Urinary endotoxin excretion and urinary tract infection following kidney transplantation.

Following kidney transplantation, urine endotoxin levels were measured among 44 patients and compared to bacterial cultures. Urine samples were collected either via transurethral catheters or - after removal of the catheter on postoperative day 4 - by midstream void. In a control group of ten healthy volunteers, urine endotoxin levels were measured daily for 10 days. Urinary endotoxin concentration was measured by means of a chromogenically modified Limulus amebocyte lysate (LAL) test. The levels among patients with positive bacteriological findings (n = 21) were always elevated ( > 0.7 EU/ml). Furthermore, there was a marked, statistically significant difference in endotoxin values between samples with bacterial growth and samples with fungal or without any growth (P < 0.001). All 21 of the 44 patients with urinary tract infection (UTI) were endotoxin-positive. Seven more patients who received antibiotics had elevated urinary endotoxin levels, but no bacterial growth in the urine culture. No bacterial infection or significant urinary endotoxin was found in the control group. In summary, the detection of urinary endotoxin in samples obtained by either suprapubic/transurethral catheters or midstream void is an early, sensitive, and specific means of diagnosis that can be carried out even during antibiotic treatment.

Bacteria↗
PubMed2002

Endotoxin stimulates fecal pellet output in rats through a neural mechanism.

The effects of endotoxin on fecal pellet output and the neural mechanisms involved in this response were investigated in conscious rats. E. coli endotoxin (40 micro g/kg i.p.) significantly increased fecal excretion for 3 h after the injection. Water content in feces was not modified by endotoxin. Ablation of primary afferent neurons by systemic administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats prevented the stimulatory effect of endotoxin and so did abdominal vagotomy. Adrenoceptor blockade with phentolamine (5 mg/kg i.p.) + propranolol (3 mg/kg i.p.) did not modify pellet output in endotoxin-treated rats while muscarinic receptor blockade with atropine (1 mg/kg i.p.) abolished the stimulatory effect of endotoxin. Finally, the increase in pellet output induced by endotoxin was prevented in animals receiving the substance P receptor antagonist D-Pro2, D-Trp7,9-substance P (2 mg/kg i.p.) or the NO-synthase inhibitor L-NAME (10 mg/kg i.p.). None of the above treatments modified pellet output in saline-treated rats. These observations indicate that endotoxin increases fecal pellet output through a nervous reflex in which capsaicin-sensitive afferent neurons and the release of excitatory (acetylcholine and substance P) and inhibitory (NO) neurotransmitters in the colonic wall are involved.

Animals↗
PubMed2006

Exposure-response relationship between endotoxin exposure and lung function impairment in cotton textile workers.

OBJECTIVES: Preventive workplace regulations are so far not based on an ubiquitously accepted threshold for airborne endotoxin in the bioaerosol. METHODS: In a cross-sectional study, 150 employees of a cotton spinning mill underwent lung function testing. Furthermore, in a random subset of 75 textile workers cross-shift lung function test and methacholine challenges were performed. Airborne current endotoxin exposure was classified as "low", "medium", and "high" ( 100- 450 Endotoxin Units (EU)/m(3), respectively) based on endotoxin activity. RESULTS: The exposure-response relationship between current endotoxin exposure and prevalence of an obstructive ventilation pattern was significant (test for linear trend: P = 0.019); the adjusted odds ratio for high endotoxin exposure was 11.22 (95% confidence interval 1.03-121.17). Within individuals, FEV(1)/FVC% was significantly reduced after the shift (paired t test: P = 0.009) but not related to current endotoxin exposure. Twelve workers showed bronchial hyperresponsiveness (8.1% before and 12.2% after the work shift; Fisher's exact test: P = 0.021). CONCLUSION: The study among German cotton textile workers suggests an exposure-dependent effect of current endotoxin exposure on lung function impairment with significant effects above 450 EU/m(3).

Adult↗
PubMed1996

Effects of endotoxin on tone and pressure-responsiveness of preglomerular juxtamedullary vessels.

Endotoxin might affect renal vasoreactivity, but in vivo this is difficult to assess (systemic influences). Therefore, we used the in vitro blood-perfused juxtamedullary nephron preparation to study early changes in preglomerular vascular reactivity induced by exposure to endotoxin. Pressure-evoked vasomotor responses were determined videometrically by measuring steady-state inside vessel diameters at a perfusion pressure of 60 or 120 mmHg. Intraluminal application of endotoxin (primary contact with endothelium) for 120 min elicited an early (within 30 min) and sustained approximately 25% vasoconstriction from arcuate artery to the distal portions of the afferent arterioles; autoregulatory responses, indicated by pressure-induced vasoconstriction, were unchanged. When topically applied, endotoxin (primary contact with smooth muscle cells) had no vasomotor effects. Significant constrictions, and increases in autoregulatory responses were obtained when the preparation was taken from kidneys from endotoxin-treated rats. Endotoxin had no effect on efferent arteriolar dimensions. Such preferential preglomerular early vasoconstriction is consistent with the early increase in renal resistance and parallel decrease in renal blood flow and glomerular filtration observed during endotoxin shock in vivo. Our results support the concept of local, endothelium-mediated effects of endotoxin on renal vessels.

Animals↗
PubMed1985

Is platelet activating factor (PAF) a mediator of endotoxin shock?

To determine whether endogenous PAF contributes to the pathogenesis of endotoxin shock, CV-3988, a specific PAF antagonist, was injected i.v. to rats before, simultaneously with or after endotoxin. CV-3988 (5 mg/kg i.v.) injected 5 min before the endotoxin completely inhibited endotoxin (15 mg/kg i.v.)-induced hypotension, and CV-3988 (0.05-1 mg/kg i.v.) injected 7-10 min after the endotoxin rapidly reversed endotoxin-induced hypotension. A combination of CV-3988 (10 mg/kg) with endotoxin (5 mg/kg) administered i.v. improved the survival rate for 20 h or more. CV-3988 (0.05-1 mg/kg i.v.) rapidly reversed the PAF (1 microgram/kg i.v.)-induced hypotension. These findings strongly suggest that endogenous PAF may play a pivotal role in the pathogenesis of endotoxin shock.

Animals↗
PubMed1995

Comparison of the induction of cyclooxygenase and nitric oxide synthase by endotoxin in endothelial cells and macrophages.

Endotoxin causes the expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2. We have compared the ability of endotoxin to increase the activities of these enzymes in bovine aortic endothelial cells and the macrophage cell line (J774.2). Endotoxin (1 microgram ml-1; for 24 h) caused a time-dependent increase in the accumulation of cyclooxygenase metabolites from endogenous arachidonic acid, in both cell types. Cyclooxygenase activity towards exogenous arachidonic acid (30 microM; for 15 min) was also increased in both cell types. Endothelial cells and macrophages also contained comparable amounts of cyclooxygenase-2 protein after incubation with endotoxin for 24 h which was prevented by pretreatment with cycloheximide (10 micrograms ml-1; 30 min prior to endotoxin). Endotoxin for 24 h caused a time-dependent increase in nitrite accumulation in macrophages, but not in endothelial cells. Thus, endotoxin increased cyclooxygenase activity and induced cyclooxygenase-2 protein in endothelial cells and macrophages. Endotoxin also increased NO synthase activity in macrophages, but not in endothelial cells.

Amino Acid Oxidoreductases↗
PubMed1991

Endotoxin hepatotoxicity augmented by ethanol.

To determine whether alcohol increases endotoxin hepatotoxicity, we administered ethanol (4.8 g/kg body wt in 4 ml of water) to rats through a gastric tube, then immediately injected endotoxin (2, 2.5, or 3 mg/kg body wt). In the rats pretreated with ethanol, the injection of 2 mg/kg body wt of endotoxin induced a slight rise of serum transaminase. However, when 2.5 mg/kg body wt of endotoxin was given, there were no significant histopathological or biochemical differences between the rats pretreated with ethanol and those pretreated with water. Moreover, there was no significant difference in mortality rates between the rats pretreated with ethanol and the controls when 3 mg/kg body wt (LD50) of endotoxin was injected. These results suggest that acute administration of alcohol enhances endotoxin hepatotoxicity when the dose of endotoxin is small, but that the effect of alcohol is masked when larger doses of endotoxin are given.

Animals↗
PubMed1991

Role of free radicals and platelet-activating factor in the genesis of intestinal motor disturbances induced by Escherichia coli endotoxins in rats.

The effects of IV administration of Escherichia coli endotoxin on intestinal myoelectric activity was investigated in conscious fasted rats chronically implanted with nichrome electrodes in the duodenojejunum. These effects were compared with those of platelet-activating factor and were evaluated in animals pretreated with a specific platelet-activating factor antagonist, BN 52021, indomethacin, a selective prostaglandin E2 antagonist, SC 19220, and several free radical scavengers. Intravenous administration of endotoxin (E. coli S.O111:B4) at a dose of 50 micrograms/kg suppressed the migrating myoelectric complexes, which were replaced by continuous rhythmic clusters of rapidly propagated spike bursts for 114.7 +/- 19.9 minutes. Intraperitoneal platelet-activating factor (25 micrograms/kg) also inhibited the migrating myoelectric complex pattern for 146.1 +/- 24.1 minutes. Previous IV administration of BN 52021 (50 mg/kg-1) abolished the motor alterations induced by platelet-activating factor and significantly reduced to 43.1 +/- 12.2 minutes those induced by endotoxin (P less than 0.01). Indomethacin (10 mg/kg IP), injected before endotoxin or platelet-activating factor, also significantly reduced the duration of migrating myoelectric complex inhibition to 45.6 +/- 7.8 and 47.7 +/- 8.3 minutes, respectively (P less than 0.01). SC 19220 significantly reduced the effects of platelet-activating factor from 151.8 +/- 26.4 to 67.4 +/- 14.7 min (P less than 0.01). Superoxide dismutase (15,000 U/kg IV) injected before either endotoxin or platelet-activating factor shortened the migrating myoelectric complex inhibition to 45.7 +/- 9.9 and 72.9 +/- 10.4 minutes, respectively (P less than 0.01). Allopurinol and dimethylsulfoxide administered orally at 50 mg/kg 1 hour before endotoxin reduced the migrating myoelectric complex inhibition to 42.5 +/- 6.5 and 38.2 +/- 6.4 minutes, respectively (P less than 0.01). They also reduced platelet-activating factor-induced intestinal myoelectric alterations to 68.5 +/- 10.6 and 31.7 +/- 6.1 minutes, respectively (P less than 0.01). It is concluded that endogenous release of platelet-activating factor is partly responsible for the intestinal motor alterations induced by endotoxin, these effects being also mediated through the release of prostaglandins and free radicals. However, prostaglandins, as well as free radicals, appear to be partly involved in the platelet-activating factor-induced action of E. coli endotoxin on intestinal motility.

Animals↗
PubMed1994

Changes in the activities of protein kinases A, C, and M in dog heart and liver following endotoxin administration.

Changes in the activities of protein kinase A (cAMP-dependent), protein kinase C (Ca2+/phospholipid-dependent), and protein kinase M (Ca2+/calmodulin-dependent) in dog heart and liver were studied 4 hr following endotoxin injection. Protein kinases A and C were extracted and partially purified by DEAE-cellulose chromatography. Protein kinase M was extracted and partially purified by DEAE-cellulose, DEAE-Sephacel, and calmodulin-Sepharose chromatography. The results indicate that in the heart, both type I (eluted at low ionic strength) and type II (eluted at high ionic strength) protein kinase A activities were unchanged after endotoxin administration. Cardiac cytosolic protein kinase C activity was increased by 50% (p < 0.05) while the membrane-associated protein kinase C activity remained unaltered following endotoxin injection. Cardiac protein kinase M activity was decreased by 38.5% (p < 0.01) post endotoxin. In the liver, type I protein kinase A activity was unaffected while type II protein kinase A activity was decreased by 34% (p < 0.01) following endotoxin injection. Hepatic cytosolic and membrane-associated protein kinase C activities were inhibited by 37% (p < 0.01) and 53% (p < 0.01), respectively, 4 hr postendotoxin. Hepatic protein kinase M activity was decreased by 61% (p < 0.01) after endotoxin administration. These data indicate that the activities of various protein kinases in the heart and liver were modified by endotoxin administration. Since protein kinases regulate cell function through phosphorylation of various substrate proteins, a modification on protein kinase activities may contribute to the development of organ dysfunction in endotoxin shock.

Animals↗
PubMed1986

Effects of bacterial endotoxin and platelet activating factor (PAF) on human platelet aggregation in native whole blood.

The effect of bacterial endotoxins E. coli 0111:B4 or S. minnesota and platelet activating factor (1-0-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine) on platelet aggregation in native whole blood (NWB) were evaluated by impedance aggregometry. In the absence of anticoagulants the patterns of impedance changes associated with aggregation were distinct from those of clotting. Both E. coli 0111:B4 and S. minnesota endotoxins shortened the time to clot formation, but impedance changes suggestive of accelerated platelet aggregation were minimal or absent. In contrast, PAF caused an increased impedance, with oscillations characteristic of aggregation, which in some instances was superseded by the smooth impedance change associated with clotting. E. coli 0111:B4 endotoxin blocked aggregation and delayed the onset of clotting after PAF, whereas S. minnesota endotoxin accelerated platelet aggregation by PAF in ten of thirteen experiments. Incubation of E. coli 0111:B4 endotoxin and PAF markedly enhanced aggregation by PAF, whereas the effect of S. minnesota was variable. Although E. coli 0111:B4 and S. minnesota endotoxins accelerated clotting but not platelet aggregation of human NWB in vitro, their interaction with PAF is complex, depending on the type of endotoxin and individual reactivity. The findings suggest that endotoxin could interact with PAF to significantly augment possible hemorrhagic and/or thrombotic complications of septic shock in humans.

Anticoagulants↗
PubMed1986

Differential alteration of lipoxygenase and cyclooxygenase metabolism by rat peritoneal macrophages induced by endotoxin tolerance.

Altered macrophage arachidonic acid metabolism may play a role in endotoxic shock and the phenomenon of endotoxin tolerance induced by repeated injections of endotoxin. Studies were initiated to characterize both lipoxygenase and cyclooxygenase metabolite formation by endotoxin tolerant and non-tolerant macrophages in response to 4 different stimuli, i.e. endotoxin, glucan, zymosan, and the calcium ionophore A23187. In contrast to previous reports of decreased prostaglandin synthesis by tolerant macrophages, A23187-stimulated immunoreactive (i) leukotriene (LT)C4/D4 and prostaglandin (PG)E2 production by tolerant cells was greater than that by non-tolerant controls (p less than 0.001). However, A23187-stimulated i-6-keto-PGF1 alpha levels were lower in tolerant macrophages compared to controls. Stimulation of prostaglandin and thromboxane (Tx)B2 synthesis by endotoxin or glucan was significantly less in tolerant macrophages compared to controls (p less than 0.05). iLTC4/D4 production was not significantly stimulated by endotoxin or glucan, but was stimulated by zymosan in the non-tolerant cells. Synthesis of iLTB4 by control macrophages was stimulated by endotoxin (p less than 0.01). These results demonstrate that arachidonic acid metabolism via the lipoxygenase and cyclooxygenase pathways in macrophages is differentially altered by endotoxin tolerance.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Sex differences in hypothalamic-pituitary-adrenal responding to endotoxin challenge in the neonate: reversal by gonadectomy.

Exposure to endotoxin is known to activate hypothalamic-pituitary-adrenal (HPA) responses in both adult and neonatal animals. We have previously reported that female rat pups exhibit greater HPA responses to endotoxin challenge than males. It is unclear, however, whether observed gender differences at this early age are mediated by gonadal factors. In the present investigation we assessed the effects of neonatal gonadectomy on HPA responses to endotoxin challenge in the developing rat. On the first day of life Long-Evans rat pups were gonadectomized or subjected to sham surgery. On the third day of life the pups were injected i.p. with 0.05 mg/kg Salmonella enteritidis endotoxin. Four hours following injection, trunk blood and tissues were collected for determination of plasma hormones and median eminence corticotropin-releasing hormone (CRH) content. Intact female rat pups were found to exhibit greater plasma adrenocorticotrophic hormone (ACTH) and corticosterone responses to endotoxin challenge compared with male animals. Plasma corticosterone levels, both total and free steroid, were markedly altered by removal of gonads such that responding to endotoxin was elevated in males, while it was reduced in females. In contrast, ACTH responding in male pups was not altered following gonadectomy, whereas female ACTH responses were significantly reduced compared with endotoxin-treated intact controls. CRH levels in the median eminence were reduced following endotoxin challenge to an equivalent extent in both male and female pups and this effect was partially attenuated by the removal of gonadal hormones. These data suggest that sex differences in HPA responses to immune challenge may be mediated at different levels of the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1996

Alterations in macrophage G proteins are associated with endotoxin tolerance.

Previous studies have suggested that endotoxin tolerance induces macrophage desensitization to endotoxin through altered guanine nucleotide regulatory (G) protein function. In the present study the binding characteristics of the nonhydrolyzable GTP analogue GTP gamma [35S] to macrophage membranes from endotoxin tolerant and control rats were determined. Membranes were prepared from peritoneal macrophages harvested from rats 72 h after two sequential daily doses of vehicle or Salmonella enteritidis endotoxin (100 micrograms/kg on day 1 and 500 micrograms/kg on day 2). GTP gamma [35S] bound to a single class of sites that were saturable and displaceable in control and endotoxin tolerant macrophage membranes. The maximum specific binding of GTP gamma [35S] was significantly (P < 0.01) decreased in membranes from tolerant rats compared to control (Bmax = 39 +/- 7 pmol/mg protein in control vs. 11 +/- 2 pmol/mg protein in endotoxin tolerant; n = 5). There were no significant differences in the Kd values. To determine whether the reduced GTP gamma S binding was due to decreases in G proteins, macrophage membrane G protein content was determined by western blotting with specific antisera to Gi1,2 alpha, Gi3 alpha, Gs alpha, and the beta subunit of G. Scanning densitometric analysis demonstrated differential decreases in tolerant macrophage membrane G proteins. Gi3 alpha was reduced the most to 48 +/- 8% of controls (n = 3), and this reduction was significant compared to those of other G proteins. Gi1,2 alpha and G beta were reduced to 73 +/- 5% (n = 3) and 65 +/- 4% (n = 3) of control values, respectively. Gs alpha(L) and Gs alpha(H) were reduced to 61 +/- 5% (n = 3) and 68 +/- 3% (n = 3) of control, respectively. These results demonstrate that endotoxin tolerant macrophages exhibit decreased membrane GTP binding capacity and differential reductions in the content of specific G proteins. The cellular mechanisms leading to such alterations in G proteins and their functional significance in the acquisition of endotoxin tolerance merit further investigation.

Animals↗
PubMed1995

Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis.

Tumor necrosis factor-alpha (TNF alpha), a cytokine that is produced in a variety of inflammatory diseases associated with cholestasis, is believed to be the primary mediator of the systemic effects of endotoxin. Thus, we have investigated the role of TNF alpha in the pathogenesis of endotoxin-induced cholestasis in intact animals, and in the uptake of taurocholate by cultured hepatocytes. Male Sprague-Dawley rats received either intravenous (IV) endotoxin (7.5 mg/kg) or monoclonal anti-TNF alpha antibody followed by endotoxin. Basal bile flow and bile salt excretion were measured for a 2-hour period, after which all animals received an IV bolus of taurocholate (10 mumol/100 g body weight). Endotoxin decreased basal bile flow by 41% and bile salt stimulated bile flow by 38% (n = 12; P < .01). Basal bile salt excretion was decreased 86% after endotoxin administration. Passive immunization with anti-TNF alpha antibody blocked this endotoxin-associated cholestasis. In addition, rat hepatocytes were isolated and cultured in the presence of either endotoxin (10 micrograms/mL) or TNF alpha (100 ng/mL) for 24 hours. These primary hepatocyte cultures exhibited a dose- and time-dependent, noncompetitive, inhibition of taurocholate uptake. We postulate that TNF alpha is an important mediator of the cholestasis of sepsis.

Animals↗
PubMed1990

Effects of endotoxin infusion on circulating levels of eicosanoids, progesterone, cortisol, glucose and lactic acid, and abortion in pregnant cows.

The effects of Escherichia coli endotoxin infusions (1.0 or 2.5 micrograms kg-1 over 6 h) on pregnancy were investigated in cows in the first, second and third trimester of gestation. Endotoxin increased the plasma levels of prostaglandins (PGs), thromboxane B2 and cortisol, and decreased progesterone. The severity of the clinical signs and the magnitude of the increases in plasma PGs, thromboxane B2 and cortisol tended to depend on the dose of endotoxin, but were independent of the gestation period. There was hyperglycemia followed by hypoglycemia and lactic acidemia. Hyperglycemia and lactic acidemia were significant only at the high dose of endotoxin. Endotoxin infusion at both doses caused a preferential mobilization of oleic acid from adipose tissue, and also had some effects on the mobilization of palmitic and stearic acids during the post-infusion period. The cows in the first trimester of gestation were more sensitive to the abortifacient effect of endotoxin than cows in the second and third trimester of gestation. The results of this study indicate that the mechanism of endotoxin-induced abortion in cows initially involves a prolonged release of PGF2 alpha and its subsequent stimulant effect on uterine smooth muscle contraction and luteolytic effect leading to a gradual decline in the plasma levels of progesterone. It was concluded that pregnancy terminates in the absence of an adequate level of progesterone, especially during the first trimester of gestation, when progesterone of extraluteal origin is not yet available, coupled with the PGF2 alpha-induced propulsive contraction of the uterus. In addition, the metabolic and circulatory failures in severe cases of endotoxemia, especially at the high dose of endotoxin, resulting either directly or indirectly via the release of various autacoids, catecholamines and cortisol, may also contribute to the termination of pregnancy at any stage of gestation.

Abortion, Veterinary↗