{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:53:23Z","timestamp":1762102403949},"reference-count":33,"publisher":"American Veterinary Medical Association (AVMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"s001\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To evaluate effects of poly(ADP-ribose) polymerase-1 (PARP1) inhibitors on the production of tumor necrosis factor-\u03b1 (TNF-\u03b1) by interferon-\u03b3 (IFN-\u03b3)\u2013 and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of horses as an in vitro model of inflammation in horses.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s002\">\n<jats:title>SAMPLE<\/jats:title>\n<jats:p>1,440 samples of PBMCs from 6 healthy research horses.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s003\">\n<jats:title>PROCEDURES<\/jats:title>\n<jats:p>From heparinized whole blood samples, PBMC cultures were obtained. An initial dose-response trial on 48 PBMC samples from 2 horses (24 samples each) was used to determine concentrations of IFN-\u03b3 and LPS for use as low- and high-level stimulation concentrations. Seventy-two PBMC samples from 6 horses were assigned equally to 1 of 4 PARP1 inhibition categories: no PARP1 inhibitor (PARP1 inhibition control); 2-((<jats:italic>R<\/jats:italic>)-2-methylpyrrolidin-2-yl)-1<jats:italic>H<\/jats:italic>-benzimidazole-4-carbozamide dihydrochloride (ABT888);4-(3-(1-(cyclopropanecarbonyl)piperazine-4-carbonyl)-4-fluorobenzyl)phthalazin-1(2<jats:italic>H<\/jats:italic>)-one (AZD2281); or <jats:italic>N<\/jats:italic>-(6-oxo-5,6-dihydrophenanthridin-2-yl) -<jats:italic>N,N<\/jats:italic>-dimethylacetamide hydrochloride (PJ34). Samples of PBMCs from each horse and each PARP1 inhibition category were then assigned to 1 of 3 levels of IFN-\u03b3 and LPS stimulation: none (control), low stimulation, or high stimulation. After a 24-hour incubation period, a TNF-\u03b1 ELISA was used to measure TNF-\u03b1 concentration in the supernatant. Results were compared across treatments and for each horse. Data were analyzed with repeated-measures ANOVA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s004\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Median TNF-\u03b1 concentration was significantly lower for PJ34-treated, high-level stimulated PBMCs than for PARP1 inhibition control, high-level stimulated PBMCs; however, no other meaningful differences in TNF-\u03b1 concentration were detected among the inhibition and stimulation combinations.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s005\">\n<jats:title>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:title>\n<jats:p>Findings suggested that PJ34 PARP1 inhibition may reduce TNF-\u03b1 production in horses, a potential benefit in reducing inflammation and endotoxin-induced damage in horses.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.80.7.663","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T13:02:40Z","timestamp":1561640560000},"page":"663-669","source":"Crossref","is-referenced-by-count":2,"title":["In vitro effects of poly(ADP-ribose) polymerase inhibitors on the production of tumor necrosis factor-\u03b1 by interferon- \u03b3 \u2013 and lipopolysaccharide-stimulated peripheral blood mononuclear cells of horses"],"prefix":"10.2460","volume":"80","author":[{"given":"Cristina","family":"Cacciolatti","sequence":"first","affiliation":[{"name":"1Dipartimento di Scienze Veterinarie, Universit\u00e0 degli Studi di Torino, Grugliasco, TO, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirella L.","family":"Meyer-Ficca","sequence":"additional","affiliation":[{"name":"2Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Pennsylvania, PA 19104."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise L.","family":"Southwood","sequence":"additional","affiliation":[{"name":"3Department of Clinical Studies\u2013New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph G.","family":"Meyer","sequence":"additional","affiliation":[{"name":"2Department of Animal Biology and Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Pennsylvania, PA 19104."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Bertolotti","sequence":"additional","affiliation":[{"name":"1Dipartimento di Scienze Veterinarie, Universit\u00e0 degli Studi di Torino, Grugliasco, TO, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Zarucco","sequence":"additional","affiliation":[{"name":"1Dipartimento di Scienze Veterinarie, Universit\u00e0 degli Studi di Torino, Grugliasco, TO, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Equine Vet J","first-page":"296","article-title":"Survival and complication rates in 300 horses undergoing surgical treatment of colic. 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