Research Article
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Does Low Dose N-Acetylcysteine Administration Enhance Diabetic Wound Healing?

Year 2021, , 117 - 131, 31.03.2021
https://doi.org/10.18185/erzifbed.845095

Abstract

The aim of this study to establish the effect of systemic N-acetylcysteine (NAC) administration on the oxidative–antioxidative balance, inflammatory markers, and collagen production during wound healing in diabetes. A total of 24 male Wistar albino rats were randomly divided into 4 groups: control, streptozotocin-induced diabetic model, NAC treatment group, and streptozotocin-induced diabetic model with NAC treatment. The dorsal circular wound model was created in model rats and systemic NAC application (IP, 60 mg/kg) was performed for 7 days in rats in the treatment groups. Lipid peroxidation, antioxidative parameters, NOx levels, and amount of collagen in wound tissue were determined by spectrophotometric methods. Inflammatory markers of wound tissue were detected by ELISA. In the wound tissues of untreated diabetic rats, lipid peroxidation and inflammatory markers were significantly increased. Superoxide dismutase and catalase activities, glutathione and NOx levels, and collagen production were significantly reduced. Following systemic NAC administration, antioxidant status and NOx levels were significantly improved and lipid peroxidation and inflammatory marker levels were remarkably reduced. Additionally, in the diabetic model-NAC treatment group, collagen production and wound contraction were significantly increased. Systemic NAC administration accelerates wound healing in diabetes by reducing oxidative stress and inflammation and increasing collagen production. As a consequence, systemic NAC therapy can be effective in ameliorating wound healing in diabetes.

Supporting Institution

Giresun Üniversitesi BAP

Project Number

FEN-BAP-A-150219-66

Thanks

The author thanks Giresun University Central Research Laboratory Application and Research Center (GRUMLAB) and the former director of the center Assoc. Prof. Dr. Murat YOLCU for their support.

References

  • Adil M., Amin S.S., Mohtashim M., 2018. “N-acetylcysteine in dermatology”, Indian J. Dermatol. Venereol. Leprol. 84, 652-659.
  • Aebi H., 1984. “Catalase in vitro”, Methods Enzymol. 105, 121-126.
  • Aktunc E., Ozacmak V.H., Ozacmak H.S., Barut F., Buyukates M., Kandemir O., Demircan N., 2010. “N-acetyl cysteine promotes angiogenesis and clearance of free oxygen radicals, thus improving wound healing in an alloxan-induced diabetic mouse model of incisional wound”, Clin. Exp. Dermatol. 35, 902-909.
  • Aldini G., Altomare A., Baron G., Vistoli G., Carini M., Borsani L., Sergio F., 2018. “N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why”, Free Radi.c Res. 52, 751-762.
  • AlMatar M., Batool T., Makky E.A., 2016. “Therapeutic Potential of N-Acetylcysteine for Wound Healing, Acute Bronchiolitis, and Congenital Heart Defect”, Curr. Drug. Metab. 17, 156-167.
  • Aykaç G., Uysal M., Yalçin A.S., Koçak-Toker N., Sivas A., Öz H., 1985. “The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats” Toxicology. 36, 71-76.
  • Boniakowski A.E., Kimball A.S., Jacobs B.N., Kunkel S.L., Gallagher K.A., 2017. “Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing”, J. Immunol. 199, 17-24.
  • Brocke T. and Barr J., 2020. “The History of Wound Healing” Surg. Clin. North. Am., 100, 787-806.
  • Buege J.A. and Aust S.D., 1978. “Microsomal lipid peroxidation”. Methods Enzymol. 52, 302-310.
  • Cano-Sanchez M., Lancel S., Boulanger E., Neviere R., 2018. “Targeting Oxidative Stress and Mitochondrial Dysfunction in the Treatment of Impaired Wound Healing: A Systematic Review”, Antioxidants (Basel). 7, 98. de Andrade K.Q., Moura F.A., dos Santos J.M., de Araújo O.R., de Farias Santos J.C., Goulart M.O., 2015. “Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine”, Int. J. Mol. Sci. 16, 30269-30308.
  • Demir E.O., Cakmak G.K., Bakkal H., Turkcu U.O., Kandemir N., Demir A.S., Tascilar O., 2011. “N-acetyl-cysteine improves anastomotic wound healing after radiotherapy in rats”, J. Invest. Surg. 24, 151-158. den Dekker A., Davis F.M., Kunkel S.L., Gallagher K.A., 2019. “Targeting epigenetic mechanisms in diabetic wound healing”, Transl. Res. 204, 39-50.
  • Deveci M., Gilmont R.R., Dunham W.R., Mudge B.P., Smith D.J., Marcelo C.L., 2005. “Glutathione enhances fibroblast collagen contraction and protects keratinocytes from apoptosis in hyperglycaemic culture”, Br. J. Dermatol. 152: 217-224.
  • Dunnill C., Patton T., Brennan J., Barrett J., Dryden M., Cooke J., Leaper D., Georgopoulos N.T., 2017. “Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process”, Int. Wound J. 14, 89-96.
  • Ezhilarasu H., Vishalli D., Dheen S.T., Bay B.H., Srinivasan D.K., 2020. “Nanoparticle-Based Therapeutic Approach for Diabetic Wound Healing”, Nanomaterials (Basel). 10, 1234.
  • Fard M.T., Arulselvan P., Karthivashan G., Adam S.K., Fakurazi S., 2015. “Bioactive Extract from Moringa oleifera Inhibits the Pro-inflammatory Mediators in Lipopolysaccharide Stimulated Macrophages”, Pharmacogn. Mag. 11, 556-563.
  • Fui L.W., Lok M.P.W., Govindasamy V., Yong T.K., Lek T.K., Das A.K., 2019. “Understanding the multifaceted mechanisms of diabetic wound healing and therapeutic application of stem cells conditioned medium in the healing process”, J. Tissue Eng. Regen. Med. 13, 2218-2233.
  • Güntürk I., Yazici C., Köse S.K., Dağli F., Yücel B., Yay A.H., 2019. “The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin-induced nephrotoxicity: a rat model”, Turk J. Med. Sci. 49, 1789-1799.
  • Ismael M.A., Talbot S., Carbonneau C.L., Beauséjour C..M, Couture R., 2008. “Blockade of sensory abnormalities and kinin B(1) receptor expression by N-acetyl-L-cysteine and ramipril in a rat model of insulin resistance”, Eur. J. Pharmacol. 589, 66-72.
  • Janeczek M., Moy L., Riopelle A., Vetter O., Reserva J., Tung R., Swan J., 2019. “The Potential Uses of N-acetylcysteine in Dermatology: A Review”, J. Clin. Aesthet. Dermatol. 12, 20-26.
  • Kaneto H., Kajimoto Y., Miyagawa J., Matsuoka T., Fujitani Y., Umayahara Y., Hanafusa T., Matsuzawa Y., Yamasaki Y., Hori M., 1999. “Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity”, Diabetes. 48, 2398-2406.
  • Kim J.H., Yang B., Tedesco A., Lebig E.G.D., Ruegger P.M., Xu K., Borneman J., Martins-Green M., 2019. “High Levels of Oxidative Stress and Skin Microbiome are Critical for Initiation and Development of Chronic Wounds in Diabetic Mice”, Sci. Rep. 9, 19318.
  • Kitano T., Yamada H., Kida M., Okada Y., Saika S., Yoshida M., 2017. “Impaired Healing of a Cutaneous Wound in an Inducible Nitric Oxide Synthase-Knockout Mouse”, Dermatol. Res. Pract. 2017, 2184040.
  • Lasram M.M., Dhouib I.B., Annabi A., El Fazaa S., Gharbi N., 2015. “A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development”, Clin. Biochem. 48, 1200-1208.
  • Li J., Chou H., Li L., Li H., Cui Z., 2020. “Wound healing activity of neferine in experimental diabetic rats through the inhibition of inflammatory cytokines and nrf-2 pathway”, Artif. Cells Nanomed. Biotechnol. 48, 96-106.
  • Li W., Li W., Leng Y., Xiong Y., Xue R., Chen R., Xia Z., 2020. “Mechanism of N-acetylcysteine in alleviating diabetic myocardial ischemia reperfusion injury by regulating PTEN/Akt pathway through promoting DJ-1”, Biosci. Rep. 40, BSR20192118.
  • Li Y. and Lee P.I., 2010. “Controlled nitric oxide delivery platform based on S-nitrosothiol conjugated interpolymer complexes for diabetic wound healing”, Mol. Pharm. 7, 254-266.
  • Luc K., Schramm-Luc A., Guzik T.J., Mikolajczyk T.P., 2017. “Oxidative stress and inflammatory markers in prediabetes and diabetes”, J. Physiol. Pharmacol. 70, doi: 10.26402/jpp.2019.6.01.
  • Malone-Povolny M.J., Maloney S.E., Schoenfisch M.H., 2019. “Nitric Oxide Therapy for Diabetic Wound Healing”, Adv. Healthc. Mater. 8, e1801210.
  • Mikolka P., Kopincova J., Mikusiakova L.T., Kosutova P., Calkovska A., Mokra D., 2016. “Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury”, Adv. Exp. Med. Biol. 934, 63-75.
  • Miranda K.M., Espey M.G., Wink D.A., 2001. “A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite”, Nitric Oxide. 5, 62-71.
  • Moreno M.L., Escobar J., Izquierdo-Álvarez A., Gil A., Pérez S, Pereda J., Zapico I., Vento M., Sabater L., Marina A., Martínez-Ruiz A., Sastre J., 2014. “Disulfide stress: a novel type of oxidative stress in acute pancreatitis”, Free Radic. Bio.l Med. 70, 265-277.
  • Muhammad A.A., Arulselvan P., Cheah P.S., Abas F., Fakurazi S., 2016. “Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model”, Drug Des. Devel. Ther. 10, 1715-1730.
  • Ozkaya H., Omma T., Bag Y.M., Uzunoglu K., Isildak M., Duymus M.E., Kismet K., Senes M., Fidanci V., Celepli P., Hucumenoglu S., Aral Y., 2019. “Topical and Systemic Effects of N-acetyl Cysteine on Wound Healing in a Diabetic Rat Model”, Wounds. 31, 91-96.
  • Ponrasu T. and Suguna L., 2012. “Efficacy of Annona squamosa on wound healing in streptozotocin-induced diabetic rats” Int. Wound J. 9, 613-623.
  • Ribeiro G., Roehrs M., Bairros A., Moro A., Charão M., Araújo F., Valentini J., Arbo M., Brucker N., Moresco R., Leal M., Morsch V., Garcia S.C., 2011. “N-acetylcysteine on oxidative damage in diabetic rats”, Drug and Chemical Toxicology. 34, 467-474.
  • Samuni Y., Goldstein S., Dean O.M., Berk M., 2013. “The chemistry and biological activities of N-acetylcysteine”, Biochim. Biophys. Acta.1830, 4117-4129.
  • Schneider R. Jr., Bandiera S., Souza D.G., Bellaver B., Caletti G., Quincozes-Santos A., Elisabetsky E., Gomez R., 2017. “N-acetylcysteine Prevents Alcohol Related Neuroinflammation in Rats”, Neurochem. Res. 42, 2135-2141.
  • Shen F.C., Weng S.W., Tsao C.F., Lin H.Y., Chang C.S., Lin C.Y., Lian W.S., Chuang J.H., Lin T.K., Liou C.W., Wang P.W., 2018. “Early intervention of N-acetylcysteine better improves insulin resistance in diet-induced obesity mice”, Free Radic. Res. 52, 1296-1310.
  • Sun Y., Oberley L.W., Li Y., 1988. “A simple method for clinical assay of superoxide dismutase”, Clin. Chem. 34, 497-500.
  • Thi P.L., Lee Y., Tran D.L., Thi T.T.H., Kang J.I., Park K.M., Park K.D., 2020. “In situ forming and reactive oxygen species-scavenging gelatin hydrogels for enhancing wound healing efficacy”, Acta Biomater.103, 142-152.
  • Tort S., Demiröz F.T., Coşkun Cevher Ş., Sarıbaş S., Özoğul C., Acartürk F., 2020. “The effect of a new wound dressing on wound healing: Biochemical and histopathological evaluation”, Burns. 46, 143-155.
  • Wang T., Mao X., Li H., Qiao S., Xu A., Wang J., Lei S.., Liu Z, Ng K.F., Wong G.T., Vanhoutte P.M., Irwin M.G., Xia Z., 2013. “N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes”, Free Radic. Biol. Med. 63, 291-303.
  • Westby M., Norman G., Vedhara K., Game F., Cullum N., 2020. “Psychosocial and behavioural prognostic factors for diabetic foot ulcer development and healing: a systematic review”, Diabet. Med. 37, 1244–1255.
  • Witte M.B., Thornton F.J., Tantry U., Barbul A., 2002. “L-Arginine supplementation enhances diabetic wound healing: involvement of the nitric oxide synthase and arginase pathways”, Metabolism. 51, 1269-1273.
  • Wu G., Bazer F.W., Burghardt R.C., Johnson G.A., Kim S.W., Knabe D.A., Li P., Li X., McKnight J.R., Satterfield M.C., Spencer T.E., 2011. “Proline and hydroxyproline metabolism: implications for animal and human nutrition”, Amino Acids. 40, 1053-1063.
  • Yilmaz B., Türkçü G., Şengül E., Gül A., Özkurt F.E., Akdağ M., 2015. “Efficacy of N-Acetylcysteine on Wound Healing of Nasal Mucosa” J. Craniofac. Surg. 26, e422-426
  • Zayed M.A., Wei X., Park K.M., Belaygorod L., Naim U., Harvey J., Yin L., Blumer K., Semenkovich C.F., 2017. “N-Acetylcysteine accelerates amputation stump healing in the setting of diabetes” FASEB J. 31, 2686-2695.

Düşük Dozda N-Asetilsistein Uygulaması Diyabetik Yara İyileşmesini Hızlandırır mı?

Year 2021, , 117 - 131, 31.03.2021
https://doi.org/10.18185/erzifbed.845095

Abstract

Oksidatif stres ve kalıcı inflamasyon, diyabetik yara komplikasyonlarının gelişmesinde önemli rol oynar. N-Asetilsistein (NAC), antioksidan özelliklerinden dolayı yara iyileşmesini hızlandıran bir amino asit türevidir. Bu çalışmanın amacı, sistemik NAC uygulamasının diyabetik yara iyileşmesinde oksidatif stres, inflamatuar belirteçler ve kollajen üretimi üzerindeki etkisini değerlendirmektir. Wistar sıçanlarda diyabet indüksiyonu, streptozotosinin intraperitoneal olarak uygulanmasıyla yapılmıştır. Diyabetik sıçanlarda dorsal dairesel bir yara oluşturulmuştur. NAC'nin yara iyileştirme potansiyelini değerlendirmek için denekler intraperitoneal olarak NAC (60 mg / kg) ile tedavi edilmiştir. Diyabetik sıçanların yara dokularında lipid peroksidasyonu ve inflamatuar belirteçler önemli ölçüde artmıştır (p<0.05). Diyabetik grupta süperoksit dismutaz ve katalaz aktiviteleri, glutatyon ve NOx seviyeleri ve kollajen üretimi anlamlı olarak azalmıştır (p<0.05). NAC uygulaması, diyabetik gruba kıyasla, tedavi edilen diyabetik grupta antioksidan durumu ve NOx düzeylerini arttırmış, lipid peroksidasyonunu ve inflamatuar belirteç düzeylerini düşürmüştür (p<0.05). Ayrıca diyabetik NAC tedavi grubunda kollajen üretimi anlamlı olarak artmış ve yara alanı diyabetik gruba göre anlamlı olarak küçülmüştür (p<0.05). Düşük doz NAC uygulamasının, oksidatif stresi ve inflamasyonu azaltarak ve kollajen üretimini artırarak diyabetik yara iyileşmesinde etkili olduğu bulunmuştur.

Project Number

FEN-BAP-A-150219-66

References

  • Adil M., Amin S.S., Mohtashim M., 2018. “N-acetylcysteine in dermatology”, Indian J. Dermatol. Venereol. Leprol. 84, 652-659.
  • Aebi H., 1984. “Catalase in vitro”, Methods Enzymol. 105, 121-126.
  • Aktunc E., Ozacmak V.H., Ozacmak H.S., Barut F., Buyukates M., Kandemir O., Demircan N., 2010. “N-acetyl cysteine promotes angiogenesis and clearance of free oxygen radicals, thus improving wound healing in an alloxan-induced diabetic mouse model of incisional wound”, Clin. Exp. Dermatol. 35, 902-909.
  • Aldini G., Altomare A., Baron G., Vistoli G., Carini M., Borsani L., Sergio F., 2018. “N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why”, Free Radi.c Res. 52, 751-762.
  • AlMatar M., Batool T., Makky E.A., 2016. “Therapeutic Potential of N-Acetylcysteine for Wound Healing, Acute Bronchiolitis, and Congenital Heart Defect”, Curr. Drug. Metab. 17, 156-167.
  • Aykaç G., Uysal M., Yalçin A.S., Koçak-Toker N., Sivas A., Öz H., 1985. “The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats” Toxicology. 36, 71-76.
  • Boniakowski A.E., Kimball A.S., Jacobs B.N., Kunkel S.L., Gallagher K.A., 2017. “Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing”, J. Immunol. 199, 17-24.
  • Brocke T. and Barr J., 2020. “The History of Wound Healing” Surg. Clin. North. Am., 100, 787-806.
  • Buege J.A. and Aust S.D., 1978. “Microsomal lipid peroxidation”. Methods Enzymol. 52, 302-310.
  • Cano-Sanchez M., Lancel S., Boulanger E., Neviere R., 2018. “Targeting Oxidative Stress and Mitochondrial Dysfunction in the Treatment of Impaired Wound Healing: A Systematic Review”, Antioxidants (Basel). 7, 98. de Andrade K.Q., Moura F.A., dos Santos J.M., de Araújo O.R., de Farias Santos J.C., Goulart M.O., 2015. “Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine”, Int. J. Mol. Sci. 16, 30269-30308.
  • Demir E.O., Cakmak G.K., Bakkal H., Turkcu U.O., Kandemir N., Demir A.S., Tascilar O., 2011. “N-acetyl-cysteine improves anastomotic wound healing after radiotherapy in rats”, J. Invest. Surg. 24, 151-158. den Dekker A., Davis F.M., Kunkel S.L., Gallagher K.A., 2019. “Targeting epigenetic mechanisms in diabetic wound healing”, Transl. Res. 204, 39-50.
  • Deveci M., Gilmont R.R., Dunham W.R., Mudge B.P., Smith D.J., Marcelo C.L., 2005. “Glutathione enhances fibroblast collagen contraction and protects keratinocytes from apoptosis in hyperglycaemic culture”, Br. J. Dermatol. 152: 217-224.
  • Dunnill C., Patton T., Brennan J., Barrett J., Dryden M., Cooke J., Leaper D., Georgopoulos N.T., 2017. “Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process”, Int. Wound J. 14, 89-96.
  • Ezhilarasu H., Vishalli D., Dheen S.T., Bay B.H., Srinivasan D.K., 2020. “Nanoparticle-Based Therapeutic Approach for Diabetic Wound Healing”, Nanomaterials (Basel). 10, 1234.
  • Fard M.T., Arulselvan P., Karthivashan G., Adam S.K., Fakurazi S., 2015. “Bioactive Extract from Moringa oleifera Inhibits the Pro-inflammatory Mediators in Lipopolysaccharide Stimulated Macrophages”, Pharmacogn. Mag. 11, 556-563.
  • Fui L.W., Lok M.P.W., Govindasamy V., Yong T.K., Lek T.K., Das A.K., 2019. “Understanding the multifaceted mechanisms of diabetic wound healing and therapeutic application of stem cells conditioned medium in the healing process”, J. Tissue Eng. Regen. Med. 13, 2218-2233.
  • Güntürk I., Yazici C., Köse S.K., Dağli F., Yücel B., Yay A.H., 2019. “The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin-induced nephrotoxicity: a rat model”, Turk J. Med. Sci. 49, 1789-1799.
  • Ismael M.A., Talbot S., Carbonneau C.L., Beauséjour C..M, Couture R., 2008. “Blockade of sensory abnormalities and kinin B(1) receptor expression by N-acetyl-L-cysteine and ramipril in a rat model of insulin resistance”, Eur. J. Pharmacol. 589, 66-72.
  • Janeczek M., Moy L., Riopelle A., Vetter O., Reserva J., Tung R., Swan J., 2019. “The Potential Uses of N-acetylcysteine in Dermatology: A Review”, J. Clin. Aesthet. Dermatol. 12, 20-26.
  • Kaneto H., Kajimoto Y., Miyagawa J., Matsuoka T., Fujitani Y., Umayahara Y., Hanafusa T., Matsuzawa Y., Yamasaki Y., Hori M., 1999. “Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity”, Diabetes. 48, 2398-2406.
  • Kim J.H., Yang B., Tedesco A., Lebig E.G.D., Ruegger P.M., Xu K., Borneman J., Martins-Green M., 2019. “High Levels of Oxidative Stress and Skin Microbiome are Critical for Initiation and Development of Chronic Wounds in Diabetic Mice”, Sci. Rep. 9, 19318.
  • Kitano T., Yamada H., Kida M., Okada Y., Saika S., Yoshida M., 2017. “Impaired Healing of a Cutaneous Wound in an Inducible Nitric Oxide Synthase-Knockout Mouse”, Dermatol. Res. Pract. 2017, 2184040.
  • Lasram M.M., Dhouib I.B., Annabi A., El Fazaa S., Gharbi N., 2015. “A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development”, Clin. Biochem. 48, 1200-1208.
  • Li J., Chou H., Li L., Li H., Cui Z., 2020. “Wound healing activity of neferine in experimental diabetic rats through the inhibition of inflammatory cytokines and nrf-2 pathway”, Artif. Cells Nanomed. Biotechnol. 48, 96-106.
  • Li W., Li W., Leng Y., Xiong Y., Xue R., Chen R., Xia Z., 2020. “Mechanism of N-acetylcysteine in alleviating diabetic myocardial ischemia reperfusion injury by regulating PTEN/Akt pathway through promoting DJ-1”, Biosci. Rep. 40, BSR20192118.
  • Li Y. and Lee P.I., 2010. “Controlled nitric oxide delivery platform based on S-nitrosothiol conjugated interpolymer complexes for diabetic wound healing”, Mol. Pharm. 7, 254-266.
  • Luc K., Schramm-Luc A., Guzik T.J., Mikolajczyk T.P., 2017. “Oxidative stress and inflammatory markers in prediabetes and diabetes”, J. Physiol. Pharmacol. 70, doi: 10.26402/jpp.2019.6.01.
  • Malone-Povolny M.J., Maloney S.E., Schoenfisch M.H., 2019. “Nitric Oxide Therapy for Diabetic Wound Healing”, Adv. Healthc. Mater. 8, e1801210.
  • Mikolka P., Kopincova J., Mikusiakova L.T., Kosutova P., Calkovska A., Mokra D., 2016. “Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury”, Adv. Exp. Med. Biol. 934, 63-75.
  • Miranda K.M., Espey M.G., Wink D.A., 2001. “A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite”, Nitric Oxide. 5, 62-71.
  • Moreno M.L., Escobar J., Izquierdo-Álvarez A., Gil A., Pérez S, Pereda J., Zapico I., Vento M., Sabater L., Marina A., Martínez-Ruiz A., Sastre J., 2014. “Disulfide stress: a novel type of oxidative stress in acute pancreatitis”, Free Radic. Bio.l Med. 70, 265-277.
  • Muhammad A.A., Arulselvan P., Cheah P.S., Abas F., Fakurazi S., 2016. “Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model”, Drug Des. Devel. Ther. 10, 1715-1730.
  • Ozkaya H., Omma T., Bag Y.M., Uzunoglu K., Isildak M., Duymus M.E., Kismet K., Senes M., Fidanci V., Celepli P., Hucumenoglu S., Aral Y., 2019. “Topical and Systemic Effects of N-acetyl Cysteine on Wound Healing in a Diabetic Rat Model”, Wounds. 31, 91-96.
  • Ponrasu T. and Suguna L., 2012. “Efficacy of Annona squamosa on wound healing in streptozotocin-induced diabetic rats” Int. Wound J. 9, 613-623.
  • Ribeiro G., Roehrs M., Bairros A., Moro A., Charão M., Araújo F., Valentini J., Arbo M., Brucker N., Moresco R., Leal M., Morsch V., Garcia S.C., 2011. “N-acetylcysteine on oxidative damage in diabetic rats”, Drug and Chemical Toxicology. 34, 467-474.
  • Samuni Y., Goldstein S., Dean O.M., Berk M., 2013. “The chemistry and biological activities of N-acetylcysteine”, Biochim. Biophys. Acta.1830, 4117-4129.
  • Schneider R. Jr., Bandiera S., Souza D.G., Bellaver B., Caletti G., Quincozes-Santos A., Elisabetsky E., Gomez R., 2017. “N-acetylcysteine Prevents Alcohol Related Neuroinflammation in Rats”, Neurochem. Res. 42, 2135-2141.
  • Shen F.C., Weng S.W., Tsao C.F., Lin H.Y., Chang C.S., Lin C.Y., Lian W.S., Chuang J.H., Lin T.K., Liou C.W., Wang P.W., 2018. “Early intervention of N-acetylcysteine better improves insulin resistance in diet-induced obesity mice”, Free Radic. Res. 52, 1296-1310.
  • Sun Y., Oberley L.W., Li Y., 1988. “A simple method for clinical assay of superoxide dismutase”, Clin. Chem. 34, 497-500.
  • Thi P.L., Lee Y., Tran D.L., Thi T.T.H., Kang J.I., Park K.M., Park K.D., 2020. “In situ forming and reactive oxygen species-scavenging gelatin hydrogels for enhancing wound healing efficacy”, Acta Biomater.103, 142-152.
  • Tort S., Demiröz F.T., Coşkun Cevher Ş., Sarıbaş S., Özoğul C., Acartürk F., 2020. “The effect of a new wound dressing on wound healing: Biochemical and histopathological evaluation”, Burns. 46, 143-155.
  • Wang T., Mao X., Li H., Qiao S., Xu A., Wang J., Lei S.., Liu Z, Ng K.F., Wong G.T., Vanhoutte P.M., Irwin M.G., Xia Z., 2013. “N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes”, Free Radic. Biol. Med. 63, 291-303.
  • Westby M., Norman G., Vedhara K., Game F., Cullum N., 2020. “Psychosocial and behavioural prognostic factors for diabetic foot ulcer development and healing: a systematic review”, Diabet. Med. 37, 1244–1255.
  • Witte M.B., Thornton F.J., Tantry U., Barbul A., 2002. “L-Arginine supplementation enhances diabetic wound healing: involvement of the nitric oxide synthase and arginase pathways”, Metabolism. 51, 1269-1273.
  • Wu G., Bazer F.W., Burghardt R.C., Johnson G.A., Kim S.W., Knabe D.A., Li P., Li X., McKnight J.R., Satterfield M.C., Spencer T.E., 2011. “Proline and hydroxyproline metabolism: implications for animal and human nutrition”, Amino Acids. 40, 1053-1063.
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There are 47 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Makaleler
Authors

Emine Gülçeri Güleç Peker 0000-0001-7244-0281

Project Number FEN-BAP-A-150219-66
Publication Date March 31, 2021
Published in Issue Year 2021

Cite

APA Güleç Peker, E. G. (2021). Does Low Dose N-Acetylcysteine Administration Enhance Diabetic Wound Healing?. Erzincan University Journal of Science and Technology, 14(1), 117-131. https://doi.org/10.18185/erzifbed.845095