Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model

Chalmeh, Aliasghar; Badiei, Khalil; Pourjafar, Mehrdad; Nazifi, Saeed

doi:10.1007/s00011-012-0551-6

Cited by 12 publications

(5 citation statements)

References 28 publications

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“…This indicates hyperglycemia is not causal to LPS-induced hyperinsulinemia and substantiates data from others demonstrating LPS directly acts on the pancreas (Vives-Pi et al, 2003;Bhat et al, 2014). Rationale for why marked hyperinsulinemia occurs is not clear, but insulin is important for immune cell glucose uptake and development during activation (Shimizu et al, 1983;Helderman, 1984;Calder et al, 2007;Maratou et al, 2007), and recent reports indicate that it has potent antiinflammatory actions (Chalmeh et al, 2013). Moreover, circulating NEFA were substantially blunted in LPS-Eu pigs, and this is likely due to insulin's potent antilipolytic role (Vernon, 1992).…”

Section: Discussionsupporting

confidence: 72%

Estimating glucose requirements of an activated immune system in growing pigs

Kvidera

Horst

Mayorga

et al. 2017

Journal of Animal Science

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Activated immune cells become obligate glucose utilizers, and a large i.v. lipopolysaccharide (LPS) dose causes insulin resistance and severe hypoglycemia. Therefore, study objectives were to quantify the amount of glucose needed to maintain euglycemia following an endotoxin challenge as a proxy of leukocyte glucose requirements. Fifteen fasted crossbred gilts (30.3 ± 1.7 kg) were bilaterally jugular catheterized and assigned 1 of 2 i.v. bolus treatments: control (CON; 10 mL sterile saline; = 7) or LPS challenge + euglycemic clamp (LPS-Eu; 055:B5; 5 μg/kg BW; 50% dextrose infusion to maintain euglycemia; = 8). Following administration, blood glucose was determined every 10 min and dextrose infusion rates were adjusted in LPS-Eu pigs to maintain euglycemia for 8 h. Pigs were fasted for 8 h prior to the bolus and remained fasted throughout the challenge. Rectal temperature was increased in LPS-Eu pigs relative to CON pigs (39.8 vs. 38.8°C; < 0.01). Relative to the baseline, CON pigs had 20% decreased blood glucose from 300 to 480 min postbolus ( = 0.01) whereas circulating glucose content in LPS-Eu pigs did not differ ( = 0.96) from prebolus levels. A total of 116 ± 8 g of infused glucose was required to maintain euglycemia in LPS-Eu pigs. Relative to CON pigs, overall plasma insulin, blood urea nitrogen, β-hydroxybutrate, lactate, and LPS-binding protein were increased in LPS-Eu pigs (295, 108, 29, 133, and 13%, respectively; ≤ 0.04) whereas NEFA was decreased (66%; < 0.01). Neutrophils in LPS-Eu pigs were decreased 84% at 120 min postbolus and returned to CON levels by 480 min ( < 0.01). Overall, lymphocytes, monocytes, eosinophils, and basophils were decreased in LPS-Eu pigs relative to CON pigs (75, 87, 70, and 50%, respectively; ≤ 0.05). These alterations in metabolism and the large amount of glucose needed to maintain euglycemia indicate nutrient repartitioning away from growth toward the immune system. Glucose is an important fuel for the immune system, and data from this study established that the glucose requirements of an intensely and acutely activated immune system in growing pigs are approximately 1.1 g/kg BW/h.

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Section: Discussionsupporting

confidence: 72%

Estimating glucose requirements of an activated immune system in growing pigs

Kvidera

Horst

Mayorga

et al. 2017

Journal of Animal Science

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“…However, this is not unprecedented, as the magnitude of APP production can be impaired during severe malnourishment (Doherty et al, 1993;Reid et al, 2002). Circulating insulin is also acutely increased during inflammation Kvidera et al, 2017a,b) and recent reports suggest insulin actually has potent anti-inflammatory effects (Chalmeh et al, 2013); however, differences in feed intake (and thus circulating nutrients, a major driver of insulin secretion) make this interpretation difficult. Utilizing an insulin-to-DMI ratio allows us to quantify the amount of circulating insulin per unit of DMI.…”

Section: Discussionmentioning

confidence: 99%

Characterizing effects of feed restriction and glucagon-like peptide 2 administration on biomarkers of inflammation and intestinal morphology

Kvidera

Horst

Fernández

et al. 2017

Journal of Dairy Science

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Inadequate feed consumption reduces intestinal barrier function in both ruminants and monogastrics. Objectives were to characterize how progressive feed restriction (FR) affects inflammation, metabolism, and intestinal morphology, and to investigate if glucagon-like peptide 2 (GLP2) administration influences the aforementioned responses. Twenty-eight Holstein cows (157 ± 9 d in milk) were enrolled in 2 experimental periods. Period 1 [5 d of ad libitum (AL) feed intake] served as baseline for period 2 (5 d), during which cows received 1 of 6 treatments: (1) 100% of AL feed intake (AL100; n = 3), (2) 80% of AL feed intake (n = 5), (3) 60% of AL feed intake (n = 5), (4) 40% of AL feed intake (AL40; n = 5), (5) 40% of AL feed intake + GLP2 administration (AL40G; 75 µg/kg of BW s.c. 2×/d; n = 5), or (6) 20% of AL feed intake (n = 5). As the magnitude of FR increased, body weight and milk yield decreased linearly. Blood urea nitrogen and insulin decreased, whereas nonesterified fatty acids and liver triglyceride content increased linearly with progressive FR. Circulating endotoxin, lipopolysaccharide binding protein, haptoglobin, serum amyloid A, and lymphocytes increased or tended to increase linearly with advancing FR. Circulating haptoglobin decreased (76%) and serum amyloid A tended to decrease (57%) in AL40G relative to AL40 cows. Cows in AL100, AL40, and AL40G treatments were euthanized to evaluate intestinal histology. Jejunum villus width, crypt depth, and goblet cell area, as well as ileum villus height, crypt depth, and goblet cell area, were reduced (36, 14, 52, 22, 28, and 25%, respectively) in AL40 cows compared with AL100 controls. Ileum cellular proliferation tended to be decreased (14%) in AL40 versus AL100 cows. Relative to AL40, AL40G cows had improved jejunum and ileum morphology, including increased villus height (46 and 51%), villus height to crypt depth ratio (38 and 35%), mucosal surface area (30 and 27%), cellular proliferation (43 and 36%), and goblet cell area (59 and 41%). Colon goblet cell area was also increased (48%) in AL40G relative to AL40 cows. In summary, progressive FR increased circulating markers of inflammation, which we speculate is due to increased intestinal permeability as demonstrated by changes in intestinal architecture. Furthermore, GLP2 improved intestinal morphology and ameliorated circulating markers of inflammation. Consequently, FR is a viable model to study consequences of intestinal barrier dysfunction and administering GLP2 appears to be an effective mitigation strategy to improve gut health.

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“…The NSAID flunixin inhibits the enzyme cyclooxygenase and therefore blocks the synthesis of the eicosanoid inflammatory mediators, such as PGs [ 15 , 16 ]. Furthermore, flunixin has antioxidative properties [ 17 ], and inhibits the activation of NF‑κB [ 18 ] and the increase in cytokine levels [ 19 , 20 ]. In LPS-treated mice, for instance, flunixin inhibited the increase in TNFA, interleukin 1β, and interleukin 10 [ 19 ].…”

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confidence: 99%

“…However, flunixin is unable to directly bind the LPS molecule [ 21 ]. The use of flunixin for the treatment of endotoxemia relies on its modulatory function on acute hemodynamic changes [ 20 ], i.e. changes in systemic blood pressure, cardiac output, and organ perfusion.…”

mentioning

confidence: 99%

Inhibition of lipopolysaccharide-induced suppression of luteal function in isolated perfused bovine ovaries

Storni

Bollwein

Hankele

et al. 2022

Journal of Reproduction and Development

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Recently, we observed that lipopolysaccharide (LPS) suppresses corpus luteum (CL) function in isolated perfused ovaries. It remained unclear if this suppression was due to increased luteal PGF 2α secretion or LPS-induced apoptosis. Therefore, possible impacts of PGF 2α and LPS were inhibited by a non-steroidal anti-inflammatory drug (flunixin) and an endotoxin-binding agent (polymyxin B), respectively. Bovine ovaries with a mid-cycle CL were collected immediately after slaughter and perfused for 240 min. After 50 min of equilibration, either flunixin or polymyxin B (5 μg/ml of each) were added to the perfusion medium of six ovaries, respectively. All ovaries (n = 12) were treated with E. coli LPS (0.5 μg/ml) 60 min after the onset of perfusion, and received 500 I.U. of hCG after 210 min of perfusion. Progesterone and PGF 2α were measured in the effluent perfusate every 10 and 30 min, respectively. Biopsies of the CL were collected every 60 min to determine the mRNA expression of the cytokine TNFA and factors of apoptosis ( CASP3 , -8 ). Flunixin-treatment inhibited the increase of PGF 2α after LPS-challenge that was observed in the polymyxin B-treated (PX-LPS) ovaries. After hCG-stimulation, progesterone secretion increased (P < 0.05) in group PX-LPS but not in the flunixin-treated (F-LPS) ovaries. Compared to initial values before LPS-challenge, luteal mRNA expression of TNFA and CASP3 was increased (P < 0.05) in group F-LPS at 120 and 180 min, respectively, and those of CASP8 was decreased (P < 0.05) in PX-LPS at 60 and 120 min after LPS-treatment. In conclusion, although flunixin managed to inhibit PGF 2α , it did not suffice to successfully prevent LPS-induced apoptosis. However, endotoxin-binding polymyxin B resulted in luteal responsiveness to hCG after LPS-challenge.

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Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model

Abstract: Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine.

Cited by 12 publications

References 28 publications

Estimating glucose requirements of an activated immune system in growing pigs

Estimating glucose requirements of an activated immune system in growing pigs

Characterizing effects of feed restriction and glucagon-like peptide 2 administration on biomarkers of inflammation and intestinal morphology

Inhibition of lipopolysaccharide-induced suppression of luteal function in isolated perfused bovine ovaries

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