Non-compartmental toxicokinetic studies of the Nigerian Naja nigricollis venom

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2022-06-01 DOI:10.1016/j.toxcx.2022.100122
Auwal A. Bala , Sani Malami , Yusuf Abubakar Muhammad , Binta Kurfi , Ismaila Raji , Sanusi Muhammad Salisu , Mustapha Mohammed , George Oche Ambrose , Murtala Jibril , Jacob A. Galan , Elda E. Sanchez , Basheer A.Z. Chedi
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Abstract

Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria Naja nigricollis venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We found that N. nigricollis venom contained sixteen venom protein families following a mass spectrometric analysis of the whole venom. Most of these proteins belong to the three-finger toxins family (3FTx) and venom phospholipase A2 (PLA2) with molecular weight ranging from 3 to 16 kDa. Other venom protein families were in small proportions with higher molecular weights. The N. nigricollis venom was rapidly absorbed at 0.5 h, increased after 1 h and continued to decrease until the 16th hour (Tmax), where maximum concentration (Cmax) was observed. This was followed by a decrease in concentration at the 32nd hour. The venom of N. nigricollis was found to have high volume of distribution (1250 ± 245 mL) and low clearance (29.0 ± 2.5 mL/h) with an elimination half-life of 29 h. The area under the curve (AUC) showed that the venom remaining in the plasma over 32 h was 0.0392 ± 0.0025 mg h.L−1, and the mean residence time was 43.17 ± 8.04 h. The pharmacometrics simulation suggests that the venom toxins were instantly and rapidly absorbed into the extravascular compartment and slowly moved into the central compartment. Our study demonstrates that Nigerian N. nigricollis venom contains low molecular weight toxins that are well absorbed into the blood and deep tissues. The venom could be detected in rabbit blood 48 h after intramuscular envenoming.

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尼日利亚黑瘤蛇毒液的非室室毒性动力学研究
蛇咬伤(SBE)是一个被忽视的公共卫生问题,特别是在亚洲、拉丁美洲和非洲。人们对毒液的毒性动力学,特别是非洲蛇的毒性动力学认识不足。为了模拟蛇咬伤的可能场景,我们采用酶联免疫吸附试验(ELISA)方法研究了北尼日利亚奈贾黑毛线虫毒液单次肌肉注射后家兔的毒动力学参数。我们在R包PK中使用了一种经过开发和验证的非区隔方法来确定毒液的毒性动力学参数,随后使用药物计量学建模来预测毒素在生物系统中的运动。通过质谱分析,我们发现黑毛线虫毒液含有16个毒液蛋白家族。这些蛋白大多属于三指毒素家族(3FTx)和毒液磷脂酶A2 (PLA2),分子量在3 ~ 16 kDa之间。其他毒蛋白科所占比例较小,分子量较高。黑毛线虫毒液在0.5 h被迅速吸收,1 h后呈上升趋势,并持续下降至第16小时(Tmax),此时观察到最大浓度(Cmax)。随后在第32小时浓度下降。黑螺旋体毒液分布量大(1250±245 mL),清除率低(29.0±2.5 mL/h),消除半衰期为29 h。曲线下面积(AUC)显示,黑螺旋体毒液在32 h内残留量为0.0392±0.0025 mg h. l−1;平均停留时间为43.17±8.04 h。药理学模拟表明,毒液毒素瞬间迅速被吸收到血管外腔室,缓慢进入中央腔室。我们的研究表明,尼日利亚黑毛线虫毒液含有低分子量的毒素,很好地吸收到血液和深层组织。兔肌注48 h后血中可检出毒。
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来源期刊
Toxicon: X
Toxicon: X Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
6.50
自引率
0.00%
发文量
33
审稿时长
14 weeks
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