Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology
Snake envenoming causes rapid systemic and local effects that often result in fatal or long-term disability outcomes. It seems likely that acute phase and inflammatory responses contribute to these haemorrhagic, coagulopathic, neurotoxic, nephrotoxic and local tissue destructive pathologies. However...
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MDPI AG
2022-03-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/14/4/229 |
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| author | Jaffer Alsolaiss Chloe A. Evans George O. Oluoch Nicholas R. Casewell Robert A. Harrison |
| author_facet | Jaffer Alsolaiss Chloe A. Evans George O. Oluoch Nicholas R. Casewell Robert A. Harrison |
| author_sort | Jaffer Alsolaiss |
| collection | DOAJ |
| description | Snake envenoming causes rapid systemic and local effects that often result in fatal or long-term disability outcomes. It seems likely that acute phase and inflammatory responses contribute to these haemorrhagic, coagulopathic, neurotoxic, nephrotoxic and local tissue destructive pathologies. However, the contributory role of acute phase/inflammatory responses to envenoming is under-researched and poorly understood—particularly for envenoming by sub-Saharan African venomous snakes. To provide data to help guide future studies of human patients, and to explore the rationale for adjunct anti-inflammatory medication, here we used an in vivo murine model to systematically assess acute phase and inflammatory responses of mice to ten African snake venoms. In addition to investigating snake species-specific effects of venom on the cardiovascular system and other key organs and tissues, we examined the response to intravascular envenoming by acute phase reactants, including serum amyloid A, P-selectin and haptoglobin, and several cytokines. Venoms of the spitting (<i>Naja nigricollis</i>) and forest (<i>N. melanoleuca</i>) cobras resulted in higher acute phase and inflammatory responses than venoms from the other cobras, mambas and vipers tested. <i>Naja nigricollis</i> venom also stimulated a 100-fold increase in systemic interleukin 6. Thin blood films from venom-treated mice revealed species-specific changes in red blood cell morphology, indicative of membrane abnormalities and functional damage, lymphopenia and neutrophil leukocytosis. Our ex vivo assays with healthy human blood treated with these venoms identified that <i>N. nigricollis</i> venom induced marked levels of haemolysis and platelet aggregation. We conclude that African snake venoms stimulate very diverse responses in this mouse model of acute systemic envenoming, and that venoms of the African cobras <i>N. nigricollis</i> and <i>N. melanoleuca</i>, in particular, cause marked inflammatory and non-specific acute phase responses. We also report that several African snake venoms cause haemolytic changes. These findings emphasise the importance of understanding acute responses to envenoming, and that further research in this area may facilitate new diagnostic and treatment approaches, which in turn may lead to better clinical outcomes for snakebite patients. |
| first_indexed | 2024-03-09T04:09:36Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T04:09:36Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-5a9191cb8c754611aa388e5fa61e20122023-12-03T14:01:44ZengMDPI AGToxins2072-66512022-03-0114422910.3390/toxins14040229Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite PathologyJaffer Alsolaiss0Chloe A. Evans1George O. Oluoch2Nicholas R. Casewell3Robert A. Harrison4Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UKCentre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UKKenya Snakebite Research & Intervention Centre, Institute of Primate Research, Karen, P.O. Box 24481, Nairobi 00502, KenyaCentre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UKCentre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UKSnake envenoming causes rapid systemic and local effects that often result in fatal or long-term disability outcomes. It seems likely that acute phase and inflammatory responses contribute to these haemorrhagic, coagulopathic, neurotoxic, nephrotoxic and local tissue destructive pathologies. However, the contributory role of acute phase/inflammatory responses to envenoming is under-researched and poorly understood—particularly for envenoming by sub-Saharan African venomous snakes. To provide data to help guide future studies of human patients, and to explore the rationale for adjunct anti-inflammatory medication, here we used an in vivo murine model to systematically assess acute phase and inflammatory responses of mice to ten African snake venoms. In addition to investigating snake species-specific effects of venom on the cardiovascular system and other key organs and tissues, we examined the response to intravascular envenoming by acute phase reactants, including serum amyloid A, P-selectin and haptoglobin, and several cytokines. Venoms of the spitting (<i>Naja nigricollis</i>) and forest (<i>N. melanoleuca</i>) cobras resulted in higher acute phase and inflammatory responses than venoms from the other cobras, mambas and vipers tested. <i>Naja nigricollis</i> venom also stimulated a 100-fold increase in systemic interleukin 6. Thin blood films from venom-treated mice revealed species-specific changes in red blood cell morphology, indicative of membrane abnormalities and functional damage, lymphopenia and neutrophil leukocytosis. Our ex vivo assays with healthy human blood treated with these venoms identified that <i>N. nigricollis</i> venom induced marked levels of haemolysis and platelet aggregation. We conclude that African snake venoms stimulate very diverse responses in this mouse model of acute systemic envenoming, and that venoms of the African cobras <i>N. nigricollis</i> and <i>N. melanoleuca</i>, in particular, cause marked inflammatory and non-specific acute phase responses. We also report that several African snake venoms cause haemolytic changes. These findings emphasise the importance of understanding acute responses to envenoming, and that further research in this area may facilitate new diagnostic and treatment approaches, which in turn may lead to better clinical outcomes for snakebite patients.https://www.mdpi.com/2072-6651/14/4/229snakebiteenvenomingAfrican cobra venomsex vivo human bloodin vivo murine modelacute phase proteins |
| spellingShingle | Jaffer Alsolaiss Chloe A. Evans George O. Oluoch Nicholas R. Casewell Robert A. Harrison Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology Toxins snakebite envenoming African cobra venoms ex vivo human blood in vivo murine model acute phase proteins |
| title | Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology |
| title_full | Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology |
| title_fullStr | Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology |
| title_full_unstemmed | Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology |
| title_short | Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology |
| title_sort | profiling the murine acute phase and inflammatory responses to african snake venom an approach to inform acute snakebite pathology |
| topic | snakebite envenoming African cobra venoms ex vivo human blood in vivo murine model acute phase proteins |
| url | https://www.mdpi.com/2072-6651/14/4/229 |
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