Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities
Snake venom is considered a “toxin arsenal”, and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators. Sinonatrix annularis is a type of non-venomous snake that was re...
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| Format: | Article |
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Elsevier
2022-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222012896 |
| _version_ | 1811221064084094976 |
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| author | Qi Lian Lipeng Zhong Kepu Fu Yuxin Ji Xiangyue Zhang Chunju Liu Chunhong Huang |
| author_facet | Qi Lian Lipeng Zhong Kepu Fu Yuxin Ji Xiangyue Zhang Chunju Liu Chunhong Huang |
| author_sort | Qi Lian |
| collection | DOAJ |
| description | Snake venom is considered a “toxin arsenal”, and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators. Sinonatrix annularis is a type of non-venomous snake that was reported to contain an “inhibitor cocktail”, including phospholipase A2 inhibitors (PLIs), metalloproteinase inhibitors (SVMPIs), and small serum protein (SSP). However, the sequences and activities of these components remain obscure. In this study, we performed envenomation challenges on S. annularis using venoms from Deinagkistrodon acutus, Agkistrodon halys and Naja atra. In brief, the maximum injected amount of venom was 360 mg/kg for D. acutus, 72 mg/kg for A. halys, and 18 mg/kg for N. atra. The mRNA expression of the inhibitors PLIα, PLIβ, PLIγ, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate from S. annularis (LH) was prepared and used to evaluate its inhibitory effect on snake venoms. As a result, LH showed significant neutralization of venom PLA2, mitigated hemorrhage, venom-induced muscle damage, and system toxicity. In the presence of LH, envenomated mice exhibited attenuated inflammation, apoptosis, oxidative damage, and mitigated changes in serum biochemical markers caused by venom. The study reveals the secret of “natural immunity” in snakes, namely, the “antivenom”, which consists of an inhibitor proteome or cocktail. |
| first_indexed | 2024-04-12T07:53:06Z |
| format | Article |
| id | doaj.art-4c290da55ce3497682722ad4963a0f83 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T07:53:06Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-4c290da55ce3497682722ad4963a0f832022-12-22T03:41:33ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113900Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activitiesQi Lian0Lipeng Zhong1Kepu Fu2Yuxin Ji3Xiangyue Zhang4Chunju Liu5Chunhong Huang6College of Basic Medical Sciences, Nanchang University, Nanchang 330006, Jiangxi Province, ChinaClinical Laboratory Center, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaCollege of Basic Medical Sciences, Nanchang University, Nanchang 330006, Jiangxi Province, ChinaCollege of Basic Medical Sciences, Nanchang University, Nanchang 330006, Jiangxi Province, ChinaCollege of Basic Medical Sciences, Nanchang University, Nanchang 330006, Jiangxi Province, ChinaAffiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaCollege of Basic Medical Sciences, Nanchang University, Nanchang 330006, Jiangxi Province, China; Correspondence to: No. 461, Bayi Avenue, Nanchang 330006, Jiangxi Province, China.Snake venom is considered a “toxin arsenal”, and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators. Sinonatrix annularis is a type of non-venomous snake that was reported to contain an “inhibitor cocktail”, including phospholipase A2 inhibitors (PLIs), metalloproteinase inhibitors (SVMPIs), and small serum protein (SSP). However, the sequences and activities of these components remain obscure. In this study, we performed envenomation challenges on S. annularis using venoms from Deinagkistrodon acutus, Agkistrodon halys and Naja atra. In brief, the maximum injected amount of venom was 360 mg/kg for D. acutus, 72 mg/kg for A. halys, and 18 mg/kg for N. atra. The mRNA expression of the inhibitors PLIα, PLIβ, PLIγ, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate from S. annularis (LH) was prepared and used to evaluate its inhibitory effect on snake venoms. As a result, LH showed significant neutralization of venom PLA2, mitigated hemorrhage, venom-induced muscle damage, and system toxicity. In the presence of LH, envenomated mice exhibited attenuated inflammation, apoptosis, oxidative damage, and mitigated changes in serum biochemical markers caused by venom. The study reveals the secret of “natural immunity” in snakes, namely, the “antivenom”, which consists of an inhibitor proteome or cocktail.http://www.sciencedirect.com/science/article/pii/S0753332222012896Sinonatrix annularisRNA-seq librarySnake venomInhibitors of toxinsGene expression |
| spellingShingle | Qi Lian Lipeng Zhong Kepu Fu Yuxin Ji Xiangyue Zhang Chunju Liu Chunhong Huang Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities Biomedicine & Pharmacotherapy Sinonatrix annularis RNA-seq library Snake venom Inhibitors of toxins Gene expression |
| title | Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities |
| title_full | Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities |
| title_fullStr | Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities |
| title_full_unstemmed | Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities |
| title_short | Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities |
| title_sort | hepatic inhibitors expression profiling of venom challenged sinonatrix annularis and antidotal activities |
| topic | Sinonatrix annularis RNA-seq library Snake venom Inhibitors of toxins Gene expression |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222012896 |
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