Topically Applied Cmt-2 Enhances Wound Healing in Streptozotocin Diabetic Rat Skin

Abstract

Delayed wound healing is one of the complications of diabetes mellitus, exhibited by increased wound collagenase and decreased granulation tissues. The current study compared wound healing in normal and diabetic rats, and the effects of topically applied 1% or 3% concentrations of chemically modified tetracycline-2 (CMT-2) on 6-mm circular full-thickness skin wounds healed by secondary intention. On day 7 after wounding, tissues were removed for biochemical analysis and histology. The wound granulation tissue hydroxyproline was less in the untreated diabetic rat with increased collagenase and gelatinase. Treating the diabetic rat wounds with 3% CMT-2 increased the wound hydroxyproline and decreased activities of gelatinase and collagenase. There was a delay in wound filling by granulation tissue in diabetic rats. In CMT-2-treated diabetic rats, the volume of granulation tissue was greater than that in untreated diabetic rats. CMT-2 appears to normalize wound healing in diabetic rats and may be a valuable adjunct in the treatment of chronic wounds.

The wound healing property of ethanolic extract of <i>Michelia champaca</i> flowers in diabetic rats

“…Intrinsic factors comprising cell-surface receptors, growth factors such as platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-1), transforming growth factor (TGF-β), and cell adhesion molecules such as integrins play a significant role in the coordination of intricate events during normal wound healing. 19 Diabetes is one of the factors affecting the normal course of wound healing. Diabetic wound healing is characterized by a delay in cellular infiltration and formation of granulation tissue, decreased wound collagen content, diminished wound tensile strength and prolonged epithelialization time.…”

“…Full-thickness cutaneous wounds which heal by secondary intention form granulation tissue which serves to fill the dermal defect and provide a structural framework for the deposition of newly synthesized collagen. 19 The fullthickness wound in diabetic rats is clinically relevant and comparable with impaired wound healing in human diabetes mellitus. 27 In this study, the rate of wound contraction was significantly (p<0.05) reduced in diabetic controls; MC extract showed better rate of wound contraction at 400 mg/kg oral dose.…”

“…6 Inhibition of collagenases can also increase the rate of wound filling by granulation tissue and the amount of collagen. 19 MC may stimulate cellular proliferation and migration through an as yet unknown mechanism. This was evident in the histological studies.…”

Inhibition of human gelatinases (matrix metalloproteinase-2 and matrix metalloproteinase-9) activity by zinc oxide: a possible mechanism to enhance wound healing.

“…However, the activities of MMP‐2 and MMP‐9 were shown to be increased in diabetic healing‐impaired mice when compared with non‐diabetic non‐healing‐impaired mice 8 . Topical application of chemically modified tetracycline‐2, an inhibitor of MMP activity, enhanced wound healing in diabetic rats 9 . These data indicate that elevated levels of MMPs may impair wound healing.…”

Wound Healing in Aged Normal and Ovariectomized Rats: Effects of Chemically Modified Doxycycline (CMT‐8) on MMP Expression and Collagen Synthesis

“…Tetracycline and its non‐antimicrobial derivative, CMT‐8, are able to inhibit bone loss in ovariectomized rats (for review see Sasaki et al 3). A recent study by Ramamurthy et al 4 has shown enhanced wound healing in diabetic rats with topically applied CMT‐2. In this study we describe the effect of oral administration of CMT‐8 or estrogen on the healing of skin wounds in aged female rats, 120 days post ovariectomy (OVX).…”