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镓标记的伊朗肥尾蝎毒液的制备及生物学评价

Preparation and Biological Evaluation of Gallium- Labeled Iranian Hemiscorpius Lepturus Scorpion Venom.

作者信息

Jalali Amir, Zahmatkesh Mona Haddad, Jalilian Amir Reza, Borujeni Amir Taheri, Alirezapour Behrouz

机构信息

Department of Toxicology, School of Pharmacy and Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Department of Nuclear Pharmacy, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.

出版信息

Curr Radiopharm. 2020;13(2):99-106. doi: 10.2174/1874471012666190828155227.

Abstract

BACKGROUND

The Hemiscorpius lepturus (H. lepturus) is a deadly scorpion species living in the southern Iran.

OBJECTIVE

H. lepturus induces delayed toxicity symptoms and understanding the long term biodistribution/ biokinetic of the venom is of great interest in toxicology.

METHODS

A Ga-67 labeled venom was prepared using a DOTA -conjugated venom followed by radiolabeling using 67GaCl3 at 40°C for 90 min. The purification of the radiolabeled venom was performed using size exclusion-chromatography (radiochemical purity 71%). The radiolabeled venom was stable in the final solution in the presence of human serum at 37°C for 72 hours. The tissue distribution was studied in blood, heart, liver, spleen, muscle, brain, kidney, intestine and skin tissues at the intervals of 1, 4, 24, 48 and 72 hours using tissue counting and SPECT imaging.

RESULTS

The radiolabeled venom mixture obtained with an estimated molar activity of 0.52 MBq/μg. The main accumulation tissues during the first 72 hours were kidneys, blood, liver, intestines, stomach and skin, respectively. Therefore, it is likely that H. lepturus' clinical effects and renal toxicity are primary and caused by direct effects of the H. lepturus venom.

CONCLUSION

The results have largely shown the direct clinical effects on the studied tissues during the 72-hour period and antivenom administration can strongly alleviate the toxicity effects as early as 72 hours in the management of the patients.

摘要

背景

细尾半蝎是一种生活在伊朗南部的致命蝎种。

目的

细尾半蝎会引发延迟性中毒症状,了解其毒液的长期生物分布/生物动力学在毒理学中具有重要意义。

方法

使用与DOTA偶联的毒液制备Ga-67标记的毒液,然后在40°C下用67GaCl3进行放射性标记90分钟。使用尺寸排阻色谱法对放射性标记的毒液进行纯化(放射化学纯度为71%)。放射性标记的毒液在37°C下于含有人类血清的最终溶液中72小时内保持稳定。在1、4、24、48和72小时的时间间隔,使用组织计数和SPECT成像研究血液、心脏、肝脏、脾脏、肌肉、大脑、肾脏、肠道和皮肤组织中的组织分布。

结果

获得的放射性标记毒液混合物的估计摩尔活度为0.52 MBq/μg。在最初的72小时内,主要的蓄积组织分别是肾脏、血液、肝脏、肠道、胃和皮肤。因此,细尾半蝎的临床效应和肾毒性很可能是原发性的,由细尾半蝎毒液的直接作用引起。

结论

结果在很大程度上显示了在72小时内对所研究组织的直接临床效应,在患者治疗中,抗蛇毒血清给药可早在72小时就有力地减轻毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7527549/94e30d1e3709/CRP-13-99_F1.jpg

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