{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:17:50Z","timestamp":1751429870848,"version":"3.41.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100021828","name":"DAAD","doi-asserted-by":"publisher","award":["A\/09\/04633"],"award-info":[{"award-number":["A\/09\/04633"]}],"id":[{"id":"10.13039\/100021828","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Higher Education, Sudan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Neurotoxicity is a common feature of elapid snake envenomation. There are limited studies on the toxicity of Naja nubiae venom, the Nubian spitting cobra, from north-east Africa.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used the chick biventer cervicis nerve-muscle preparation to demonstrate the neurotoxic effect of N. nubiae venom and to compare it with the potent neurotoxic cobra Naja melanoleuca venom. Venoms were separated by successive reverse-phase high-performance liquid chromatography (RP-HPLC) runs and the molecular mass of the neurotoxins was determined by matrix-assisted laser desorption\/ionization time of flight mass spectrometry (MALDI-TOF MS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Both venoms caused time-dependent inhibition of nerve-mediated twitches with a t90 value of 22.2\u00b11.9\u00a0min and 12.9\u00b11.2\u00a0min for N. nubiae and N. melanoleuca venoms, respectively. Prior incubation of some commercial antivenom (EchiTab-Plus-ICP [Costa Rica], CSL, Parkville, Victoria, Australia) and snake venom antisera [India]) did not prevent the neurotoxic effect of N. nubiae venom. The chromatographic separation of N. nubiae and N. melanoleuca venoms followed by MALDI-TOF MS analysis revealed that short-chain \u03b1-neurotoxin accounted for 8.4% of N. nubiae and 14.8% of N. melanoleuca whole venoms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>N. nubiae venom, which was previously known as cytotoxic venom, exhibits considerable in vitro neurotoxic effects on chick nerve-muscle preparations that may have consequences for antivenom development in north-east Africa.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/trstmh\/trae116","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T11:44:10Z","timestamp":1732707850000},"page":"688-696","source":"Crossref","is-referenced-by-count":0,"title":["The neurotoxic effect of <i>Naja nubiae<\/i> (Serpentes: Elapidae) venom from Sudan"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-7467","authenticated-orcid":false,"given":"Huda","family":"Khalid","sequence":"first","affiliation":[{"name":"Faculty of Science, University of Khartoum Department of Zoology, , P.O. Box 321 , Khartoum ,","place":["Sudan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maowia M","family":"Mukhtar","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum Department of Immunology, , P.O. 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Two cases","volume":"68","author":"Blaylock","year":"1985","journal-title":"S Afr Med J"},{"issue":"10","key":"2025070113063587800_bib5","first-page":"e2302","article-title":"Neurotoxicity in snakebite\u2014the limits of our knowledge","volume":"7","author":"Ranawaka","year":"2013","journal-title":"PLoS Med"},{"issue":"5","key":"2025070113063587800_bib6","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/00034983.1980.11687380","article-title":"Malumfashi endemic diseases research project. XIII. 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