Anti-inflammatory effects of retinoids and carotenoid derivatives on caspase-3–dependent apoptosis and efferocytosis of bovine neutrophils

Duquette, Stephanie; Fischer, Carrie D.; Feener, Troy; Muench, Gregory; Morck, Douglas W.; Barreda, Daniel R.; Nickerson, James G.; Buret, André G.

doi:10.2460/ajvr.75.12.1064

Cited by 23 publications

(25 citation statements)

References 55 publications

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“…Removal of β-carotene, particularly natural sources, such as alfalfa, from diets has resulted in the simultaneous, albeit unintended, removal of the naturally present β-carotene copolymers and their associated benefits. The positive effects on growth performance and health observed with OxBC in these trials coupled with similar findings in previous trials in swine (Hurnik et al, 2011; Chen et al, 2020), poultry (Kang et al, 2018) and dairy calves (Duquette et al, 2014) demonstrate that re-introduction of very low amounts of β-carotene oxygen copolymer into feeds can beneficially support the health and productivity of livestock and substantially reduce the need for in-feed antibiotics.…”

Section: Discussionsupporting

confidence: 81%

“…Results from studies in an experimental model of bovine respiratory disease (BRD) and in gestating/lactating sows demonstrate an anti-inflammatory action for OxBC. In the experimental BRD trial, animals that received dietary supplementation with OxBC had a significant increase in anti-inflammatory or pro-resolution activity in the lung (Duquette et al, 2014) while OxBC-supplementation in gestating/lactating sows led to reductions in the concentration of pro-inflammatory cytokines, TNFα and IL-8 in colostrum and milk (Chen et al, 2020). Reduced inflammation may also be partly responsible for the observed reduction in intestinal lesion severity in C. perfringens-challenged broilers (Kang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…OxBC exhibits dual immunological activities relating to: a) enhancing innate immune detection and response to pathogens (Johnston et al, 2014) and, b) an anti-inflammatory/pro-resolution action that limits the extent of over-zealous immune responses and reduces the level of background inflammation (Duquette et al, 2014; Chen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Effect of oxidized β-carotene-oxygen copolymer compound on health and performance of pre- and post-weaned pigs

Kinh

Riley²,

Nickerson³

et al. 2020

Preprint

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The discovery of naturally occurring, biologically active β-carotene-oxygen copolymer compounds in spontaneously oxidized β-carotene has stimulated interest in their potential health benefits. The copolymers, formed in Nature or synthetically by the air-oxidation of β-carotene, possess beneficial immune modulating activities that previously had been attributed to β-carotene itself. Support for these benefits is provided by previous studies showing that supplementation in feed with low parts-per-million levels of copolymer-rich, fully oxidized β-carotene (OxBC) helped reduce the negative impact of subclinical necrotic enteritis in broilers and improved growth in weaned piglets. To further assess these potential benefits, two trials were conducted in swine raised under commercial conditions in Vietnam. Trial 1, a 140-day full-grow, post-wean study with 500 28-day-old pigs, compared 2, 4 or 8 ppm OxBC against both an unsupplemented and an antibiotic control group. OxBC and antibiotics each improved growth rate, feed efficiency, and body weight compared to the control. Animals receiving 4 and 8 ppm OxBC performed better than did animals on antibiotics. In starter pigs, OxBC reduced the occurrence of diarrhea dose-dependently (4 and 8 ppm) and to a greater extent than did antibiotics. Trial 2, a 49-day study with 420 piglets, was conducted in two-stages. In Stage 1 (pre-wean), OxBC in the transition (creep) feed produced a dose-dependent trend toward increased body weight over 21 days, reaching significance at the highest inclusion level (16 ppm). In Stage 2 (post-wean), body weight gain showed a dose-dependent trend and was significant for both 8 ppm OxBC and the antibiotics at 28 days post-wean. Feed conversion was better at 8 ppm OxBC and for the antibiotic group. These findings support the concept that β-carotene-oxygen copolymers help optimize immune function, and provide validation for the effectiveness of this strategy in enhancing animal performance in the absence of in-feed antibiotics.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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Effect of oxidized β-carotene-oxygen copolymer compound on health and performance of pre- and post-weaned pigs

Kinh

Riley²,

Nickerson³

et al. 2020

Preprint

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“…The E3 ubiquitin ligase mouse double minute homolog 2 (MDM2), whose gene is transcriptionally activated by p53, can act as a direct negative regulator of NFκB by binding and inhibiting p65RelA [ 45 ]. Furthermore, ATRA-p53-induced neutrophil apoptosis may reduce inflammation in acne [ 46 – 48 ]. ATRA has also been shown to induce apoptosis and suppression of NFκB signalling in adult T cell leukaemia cells [ 49 ].…”

Section: Retinoic Acidmentioning

confidence: 99%

p53: key conductor of all anti-acne therapies

Melnik

2017

J Transl Med

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This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin’s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.

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“…The second discovery relates to the biological activity of the compound mixture, which is termed oxidised β-carotene (OxBC). In vitro and in vivo studies demonstrated the presence of immune modulating activities for OxBC, including the ability to (1) prime the innate immune system and (2) limit the extent of inflammation (7,8) . Furthermore, the newly discovered copolymers were shown to be responsible for the innate immunological activities of OxBC, while the norisoprenoids appeared to be inert with regard to immunological activity (7) .…”

mentioning

confidence: 99%

Effects of maternal supplementation with fully oxidised β-carotene on the reproductive performance and immune response of sows, as well as the growth performance of nursing piglets

Chen

Zhang

et al. 2020

Br J Nutr

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The present study was conducted to evaluate the impact of dietary fully oxidised β-carotene (OxBC, C40H60O15) supplementation during the perinatal period on immune status and productivity in a sow model. At day 85 of pregnancy, 150 sows were allocated to one of three dietary treatments with fifty sows per treatment. The three experimental diets were supplemented with 0, 4 or 8 mg/kg OxBC in the basal diet. The feeding trial was conducted from gestation day 85 until day 21 of lactation. Dietary OxBC supplementation greatly enhanced colostrum IgM, IgA and IgG levels, and the IgM and IgG content of 14-d milk. Dietary OxBC supplementation decreased the TNF-α and IL-8 levels in colostrum, as well as the TNF-α and IL-18 levels in 14-d milk. There was also a tendency towards an increase in the soluble CD14 level in 14-d milk. Although dietary treatments did not affect average daily feed intake nor backfat thickness loss during lactation, dietary OxBC supplementation tended to enhance litter weight and individual piglet weight at weaning. There was a trend towards increased lactose concentration in 14-d milk with increasing dietary OxBC. It is concluded that dietary supplementation with OxBC during the perinatal period enhances the lactose concentration of sow milk and the immune status of sows, which is reflected by improved cytokine status and immunoglobulin concentrations in colostrum and milk, and thus tending to increase litter weight and individual piglet weight at weaning. The results also provide a scientific nutritional reference for perinatal mothers due to the biological similarity between pigs and humans.

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Anti-inflammatory effects of retinoids and carotenoid derivatives on caspase-3–dependent apoptosis and efferocytosis of bovine neutrophils

Cited by 23 publications

References 55 publications

Effect of oxidized β-carotene-oxygen copolymer compound on health and performance of pre- and post-weaned pigs

Effect of oxidized β-carotene-oxygen copolymer compound on health and performance of pre- and post-weaned pigs

p53: key conductor of all anti-acne therapies

Effects of maternal supplementation with fully oxidised β-carotene on the reproductive performance and immune response of sows, as well as the growth performance of nursing piglets

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