Mesalazine based topical hydrogel formulation enhances anti-oxidant and cytokine activity in wounded STZ-induced mice
Abstract
Background: The present study is targeted to elucidate the wound healing potential of mesalazine in STZ induced diabetic mice by comparing various antioxidant, pro-inflammatory cytokine levels and other wound healing parameters at 3,7 and 14th day.
Methods: Full thickness excisional wounds of 6mm size were created on the dorsal side of STZ induced mice and topical treatment of mesalazine based different hydrogels was applied for 14 days. Wound tissues were excised on day 3, 7 and 14 for various wound healing parameters.
Results: Delayed in wound healing was observed in diabetic group which eventually got accelerated after application of ethosome based mesalazine loaded hydrogel designated as D5 in study. Significant wound contraction rate was observed in D5 group and tissue hydroxyproline and tensile strength was also elevated after treatment with mesalazine loaded ethosomal hydrogel. The level of ROS was found to be significantly decreased in SOD, CAT and GSH experiment. LPO level were found to be elevated in D5 group. Finding of levels of pro-inflammatory cytokine suggested significant decrease and showed significant elevation in vascular endothelial growth factor (VEGF).
Conclusion: D5 group of ethosome based mesalazine loaded hydrogel showed promising results in controlling all the factors to their normal range and was effective in accelerating wound 51healing in diabetic mice.
Keywords: Diabetic wounds; hydrogels; antioxidants; cytokines; VEGF; Mesalazine
Keywords:
Diabetic wounds, hydrogels, antioxidants, cytokines, VEGF, MesalazineDOI
https://doi.org/10.22270/jddt.v12i2.5384References
Bajpai S, Mishra M, Kumar H, Tripathi K, Singh SK, Pandey HP, Singh RK, “Effect of selenium on connexin expression, angiogenesis, and antioxidant status in diabetic wound healing” Biol Trace Elem Res, 2011; 144(1):327-38. https://doi.org/10.1007/s12011-011-9097-7
Brem H, Tomic-Canic M, “Cellular and molecular basis of wound healing in diabetes. J Clin Investig, 2007; 117(5):1219-22. https://doi.org/10.1172/JCI32169
Patel S, Srivastava S, Singh MR, Singh D, “Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing” Biomed Pharmacother, 2019; 112:108615. https://doi.org/10.1016/j.biopha.2019.108615
Cho H, Blatchley MR, Duh EJ and Gerecht S, “Acellular and cellular approaches to improve diabetic wound healing” Adv Drug Deliv Rev, 2018; 146:267–288. https://doi.org/10.1016/j.addr.2018.07.019
Moura J, Madureira P, Leal EC, Fonseca AC, Carvalho E, “Immune aging in diabetes and its implications in wound healing” Clin Immunol, 2019; 200:43–54. https://doi.org/10.1016/j.clim.2019.02.002
Liu J, Zheng H, Poh PS, “Hydrogels for engineering of perfusable vascular networks” Int J Mol Sci, 2015; 16:15997-16016. https://doi.org/10.3390/ijms160715997
Chen S, Shi J, Zhang M, Chen Y, Wang X, Zhang L, Tian Z, Yan Y, Li Q, Zhong W, Xing M, “Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing” Sci Rep, 2015; 5:18104.
Tong C, Hao H, Xia L, Liu J, Ti D, Dong L, Hou Q, Song H, Liu H, Zhao Y, Fu X, “Hypoxia pretreatment of bone marrow-derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hind limb ischemia” Wound Repair Regen, 2016; 24:45-56. https://doi.org/10.1111/wrr.12369
Lai HJ, Kuan CH, Wu HC, Tsai JC, Chen TM, Hsieh DJ, Wang TW, “Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing” Acta Biomater, 2014; 10:4156-4166. https://doi.org/10.1016/j.actbio.2014.05.001
Borges RS, Castle SL, “The antioxidant properties of salicylate derivatives: A possible new mechanism of anti-inflammatory activity” Bioorganic Med Chem Lett, 2015; 25(21):4808-11. https://doi.org/10.1016/j.bmcl.2015.07.001
Kaufman J, Griffiths TA, Surette MG, Ness S, Rioux KP, “Effects of Mesalamine (5-5-Aminosalicylic Acid) on Bacterial Gene Expression” Inflamm Bowel Dis, 2009; 15(7):985-96. https://doi.org/10.1002/ibd.20876
Moura RM, Hartmann RM, Licks F, Schemitt EG, Colares JR, do Couto Soares M, Fillmann LS, Fillmann HS, Marroni NP, “Antioxidant effect of mesalazine in the experimental colitis model induced by acetic acid” J Coloproctol (Rio J), 2016; 36:139-48. https://doi.org/10.1016/j.jcol.2016.03.003
Zhao M, Zhou J, Chen YH, Yuan L, Yuan MM, Zhang XQ, Hu Y, Yu H, “Folic acid promotes wound healing in diabetic mice by suppression of oxidative stress” J Nutr Sci Vitaminol, 2018; 64(1):26-33. https://doi.org/10.3177/jnsv.64.26
Xiong X, Liang J, Xu Y, Liu J, Liu Y, “The wound healing effects of the Tilapia collagen peptide mixture TY001 in streptozotocin diabetic mice” J Sci Food Agric, 2020; 100(7):2848-58. https://doi.org/10.1002/jsfa.10104
Banerjee P, Suguna L, Shanthi C, “Wound healing activity of a collagen-derived cryptic peptide” Amino Acids, 2015; 47:317–328. https://doi.org/10.1007/s00726-014-1860-6
Rashed AN, Afifi FU, Disi AM, “Simple evaluation of the wound healing activity of a crude extract of Portulaca oleracea L. (growing in Jordan) in Mus musculus JVI-1” J Ethnopharmacol, 2003; 88(2 Suppl 3):131-6. https://doi.org/10.1016/S0378-8741(03)00194-6
Beauchamp C, Fridovich I, “Superoxide dismutase: improved assays and an assay applicable to acrylamide gels” Anal Biochem, 1971; 44(1):276-287. https://doi.org/10.1016/0003-2697(71)90370-8
Ohkawa H, Ohishi N, Yagi K, “Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction” Anal Biochem, 1979; 95(2):351-358. https://doi.org/10.1016/0003-2697(79)90738-3
Aebi H, “Catalase in-vitro” Methods Enzymolo, 1984; 105:121-126. https://doi.org/10.1016/S0076-6879(84)05016-3
Mokrasch LC, Teschke EJ, “Glutathione content of cultured cells and rodent brain regions: a specific fluorometric assay” Anal Biochem, 1984; 140(2):506-509. https://doi.org/10.1016/0003-2697(84)90201-X
Baynes JW, “Role of oxidative stress in development of complications in diabetes” Diabetes, 1991; 40:405–412. https://doi.org/10.2337/diab.40.4.405
Werner S, Grose R, “Regulation of wound healing by growth factors and cytokines” Physiol Rev, 2003; 83:835–870. https://doi.org/10.1152/physrev.2003.83.3.835
Charlton A, Garzarella J, Jandeleit-Dahm KA, Jha JC, “Oxidative stress and inflammation in renal and cardiovascular complications of diabetes” Biology (Basel), 2021; 10(1):18. https://doi.org/10.3390/biology10010018
Managlia E, Katzman RB, Brown JB, Barrett TA, “Antioxidant properties of mesalamine in colitis inhibit phosphoinositide 3-kinase signaling in progenitor cells” Inflamm Bowel Dis, 2013; 19(10):2051-60. https://doi.org/10.1097/MIB.0b013e318297d741
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