Marimastat attenuates local tissue damage induced by Indonesian Trimeresurus insularis and Calloselasma rhodostoma venoms in a mouse skin model

Sofyantoro, Fajar and Susanto, Benadya Aprilia and Damayanti, Fitriana and Wihatma, Ghea Navali and Ahmad Rusmili, Muhamad Rusdi and Al Habsyi, Muhammad Kadzim and Pradani, Mutiara Puri and Syarif, Anindya Sisilia and Aisiyah, Riska Nur and Raizma, Alda Zaenida Nurul and Mutawakkil, Muhammad Ahyf and Sadewo, Imran and Nuriliani, Ardaning and Nuringtyas, Tri Rini and Yudha, Donan Satria and Raharjo, Slamet and Purwestri, Yekti Asih (2026) Marimastat attenuates local tissue damage induced by Indonesian Trimeresurus insularis and Calloselasma rhodostoma venoms in a mouse skin model. The Journal of Veterinary Medical Science, 88 (10). pp. 1625-1635. ISSN 0916-7250 E-ISSN 1347-7439

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Official URL: https://www.jstage.jst.go.jp/article/jvms/88/10/88...

Abstract

Snakebite-induced local tissue damage remains a challenge in snakebite envenoming management because venom toxins rapidly disrupt vascular and extracellular matrix integrity at the bite site. This study evaluated the inhibitory effect of marimastat, an inhibitor of zinc-dependent metalloproteinases, against local tissue damage induced by Indonesian Trimeresurus insularis and Calloselasma rhodostoma venoms in a mouse skin model. The minimum hemorrhagic dose (MHD) of C. rhodostoma venom was determined in BALB/c mice and estimated to be 7.07 µg, while the MHD of T. insularis was adopted from a previous study. Mice received intradermal injections of venom at 2× MHD, either alone or pre-incubated with marimastat at venom:marimastat ratios of 1:1, 1:5, and 1:10 based on MHD equivalents. Macroscopic hemorrhage and histopathological changes, including erythrocyte extravasation, inflammatory cell infiltration, and collagen degradation, were assessed three hours after injection. Both venoms induced marked hemorrhagic lesions and tissue damage. Marimastat reduced venom-induced hemorrhage in both models, with near-complete inhibition in the T. insularis 1:10 group and complete inhibition in the C. rhodostoma 1:10 group. Marimastat also decreased erythrocyte extravasation, inflammatory infiltration, and collagen degradation, indicating preservation of microvascular and dermal matrix integrity. These findings support the central role of snake venom metalloproteinases in local viperid tissue damage and highlight marimastat as a promising adjunctive treatment for reducing venom-induced skin injury.

Item Type:	Article (Journal)
Uncontrolled Keywords:	hemorrhage, marimastat, metalloproteinase, snakebite, venom
Subjects:	R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy Kulliyyah of Pharmacy > Department of Basic Medical Sciences
Depositing User:	Dr Muhamad Rusdi Ahmad Rusmili
Date Deposited:	13 Oct 2026 16:20
Last Update:	13 Oct 2026 16:20
Queue Number:	2026-10-Q5560
URI:	http://irep.iium.edu.my/id/eprint/131864
Indexed In:	SCOPUS, ERA, Google Scholar

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