Botrops derived hemocoagulase formulation a probable agent for diabetic wound healing
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ORIGINAL ARTICLE
Botrops derived hemocoagulase formulation a probable agent for diabetic wound healing Raghuvir Keni1 · Karthik Gourishetti1 · Manas Kinra1 · Pawan G. Nayak1 · Rekha Shenoy1 · Krishnadas Nandakumar1 · Rajesh N. Jagdale2 · K. V. Raghavendra2 · Syed Mushtaq Ahmed2 Received: 3 April 2020 / Accepted: 5 September 2020 © The Author(s) 2020
Abstract Botroclot is a marketed preparation containing hemocoagulase, which is an enzyme having coagulant activity, isolated from the snake Botrops atrox. 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. Keywords Hemocoagulase · Botrops atrox · Venom · Diabetic wound
Introduction Diabetic wounds are a common issue seen with patients. As compared to wound healing in healthy individuals, healing of the wound is delayed in case of diabetic patients. Physiologically the reason is due to impaired blood flow, diabetic neuropathy and impaired immune function. Whereas at a molecular level, the impaired cytokine production, impaired fibroblast and other cell migration and chronic inflammation The authors, Raghuvir Keni and Karthik Gourishetti, have contributed equally. * Krishnadas Nandakumar [email protected] 1
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
2
are associated with the delay in wound healing (Patel et al. 2019). Diabetic wound healing and diabetic ulcers remain an unaddressed area with no agents other than Becaplermin (Steed 1995) available to hasten the healing of wounds, howe
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