Keni Raghuvir, Gourishetti Karthik, Kinra Manas, Nayak Pawan G, Shenoy Rekha, Nandakumar Krishnadas, Jagdale Rajesh N, Raghavendra K V, Ahmed Syed Mushtaq
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104 Karnataka India.
Juggat Pharma, Jagdale Industries Pvt. Ltd., Bengaluru, 560078 Karnataka India.
3 Biotech. 2020 Oct;10(10):443. doi: 10.1007/s13205-020-02429-5. Epub 2020 Sep 18.
Botroclot is a marketed preparation containing hemocoagulase, which is an enzyme having coagulant activity, isolated from the snake This formulation is used in dental surgeries and other minor surgical wounds. However, the formulation remains untested in diabetic wounds. Hence, we proposed a study for the topical application of Botroclot in high-fat diet (HFD) + Streptozotocin (STZ) induced diabetic rats. HFD was fed initially to rats which facilitates the development of insulin resistance. Thereafter, an injection of STZ (40 mg/kg, i.p.) was given. This resulted in the development of diabetes with elevated fasting glucose and impaired glucose tolerance. After stabilization of blood glucose values, wounds were created by punch biopsy on the dorsal side of the palm of the rat to mimic the diabetic wounds frequently seen in the case of humans. Later, the application of Botroclot on these wounds was carried out for 15 days. Topical application of hemocoagulase improved the wound closure and there was a gradual decrease in inflammatory markers and a substantial increase in collagen deposition occurred. Histopathological findings indicated the same, with an increase in granulation tissue suggesting that the topical application moderately improves the wound healing in diabetic rats. We conclude that Botroclot can have a mild to moderate effect in improving collagen deposition and thus wound contraction, improving wound closure in diabetic wounds in rats. This study also establishes the basis for exploration of agents from venom-based sources in diabetic wound healing.
凝血酶是一种已上市的制剂，含有从蛇中分离出的具有凝血活性的酶——血凝酶。该制剂用于牙科手术和其他小型手术伤口。然而，该制剂在糖尿病伤口中尚未经过测试。因此，我们提出了一项关于在高脂饮食（HFD）+链脲佐菌素（STZ）诱导的糖尿病大鼠中局部应用凝血酶的研究。最初给大鼠喂食高脂饮食以促进胰岛素抵抗的发展。此后，注射链脲佐菌素（40mg/kg，腹腔注射）。这导致了糖尿病的发生，空腹血糖升高且糖耐量受损。在血糖值稳定后，通过在大鼠手掌背部进行打孔活检来制造伤口，以模拟人类常见的糖尿病伤口。之后，在这些伤口上应用凝血酶15天。局部应用血凝酶改善了伤口愈合，炎症标志物逐渐减少，胶原蛋白沉积显著增加。组织病理学结果表明了同样的情况，肉芽组织增加表明局部应用适度改善了糖尿病大鼠的伤口愈合。我们得出结论，凝血酶在改善胶原蛋白沉积从而促进伤口收缩、改善大鼠糖尿病伤口的愈合方面可产生轻度至中度的效果。本研究还为探索基于毒液来源的药物在糖尿病伤口愈合中的应用奠定了基础。
