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Effect of photobiomodulation therapy on inflammatory cytokines in healing dynamics of diabetic wounds: a systematic review of preclinical studies

Karkada G, Maiya GA, Houreld NN, Arany P, Rao Kg M, Adiga S, et al.

Arch Physiol Biochem, 2020 Dec 28.
PMID: 33370535 DOI: 10.1080/13813455.2020.1861025

CONTEXT: Delayed wound healing in diabetes mellitus (DM) is due to the overlapping phases of the healing process. The prolonged inflammation and altered levels of inflammatory cytokines lead to deformed cell proliferation. Photobiomodulation alleviates the expression of inflammatory cytokines and promotes tissue repair, thereby restoring the wound healing process.
OBJECTIVE: To find out the effect of photobiomodulation therapy (PBMT) in the healing dynamics of diabetic wounds with particular emphasis on interleukin-6, interleukin-1β, and tumour necrosis factor-α.
METHODS: Scientific databases searched using keywords of the population: DM, intervention: PBMT, and outcomes: inflammatory cytokines.
RESULTS: We have included five preclinical studies in the present systematic review for qualitative analysis. These studies evaluated the effect of PBMT at different wavelengths, dosage, and time on wound healing in DM.
CONCLUSIONS: The systematic review concludes that PBMT regulates inflammatory cytokines levels, enhances cell proliferation, and migration, thereby improving the wound healing properties.
Effect of Photobiomodulation Therapy on Oxidative Stress Markers in Healing Dynamics of Diabetic Neuropathic Wounds in Wistar Rats

Karkada G, Maiya GA, Arany P, Rao M, Adiga S, Kamath SU

Cell Biochem Biophys, 2021 Jul 30.
PMID: 34331219 DOI: 10.1007/s12013-021-01021-9

BACKGROUND: Prolonged and overlapping phases of wound healing in diabetes are mainly due to the redox imbalance resulting in the chronicity of the wound. Photobiomodulation therapy works on the principle of absorption of photon energy and its transduction into a biological response in the living tissue. It alleviates the cellular responses, thereby improving the mechanism of wound healing in diabetes.
OBJECTIVE: To find out the effect of photobiomodulation therapy of dosage 4 J/cm2 in the healing dynamics of diabetic neuropathic wounds in Wistar rats and its relation with oxidative stress markers.
METHODOLOGY: Diabetes was induced using Streptozotocin of 60 mg/kg of body weight to eighteen female Wistar rats. Neuropathy was induced by the sciatic nerve crush injury followed by an excisional wound of 2 cm2 on the back of the animal. Experimental group animals were treated with dosage 4 J/cm2 of wavelength 655 and 808 nm, and control group animals were kept unirradiated. The biomechanical, histopathological, and biochemical changes were analysed in both groups.
RESULTS: There was a reduction in mean wound healing time and an increased rate of wound contraction in the experimental group animals compared to its control group. The experimental group showed improved redox status, and histopathological findings revealed better proliferative cells, keratinisation, and epithelialization than un-irradiated controls.
CONCLUSIONS: Photobiomodulation therapy of dosage 4 J/cm2 enhanced the overall wound healing dynamics of the diabetes-induced neuropathic wound and optimised the oxidative status of the wound, thereby facilitating a faster healing process.
Dose-Response Relationship of Photobiomodulation Therapy on Matrix Metalloproteinase in Healing Dynamics of Diabetic Neuropathic Ulcers-An in vivo Study

Karkada G, Maiya GA, Arany P, Rao Kg M, Adiga S, Kamath SU

Photochem Photobiol, 2023;99(4):1172-1180.
PMID: 36477863 DOI: 10.1111/php.13754

Individuals with diabetic foot ulcers have overlapped the inflammatory, proliferative and remodeling phase, making the tissue vulnerable to delayed healing responses. We aimed to establish the dose-response relationship of photobiomodulation therapy of different doses and matrix metalloproteinases in the healing dynamics of diabetic neuropathic ulcers. Diabetes was induced in 126 Albino Wistar rats, and neuropathy was induced to the hind paw by a sciatic nerve injury method. An excisional wound was created on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12 and 15 J cm-2 and wavelength 655 nm and 808 nm was irradiated. Photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 showed better wound healing properties with optimized levels of matrix metalloproteinases-1 and 8. We observed a strong dose response in the experimental group treated with 6 and 8 J cm-2 . The findings from the present study conclude that photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 is suggestive of usefulness in diabetic neuropathic ulcer healing. Markers like matrix metalloproteinases may give a clear direction on response to the therapy. Based on the findings from the present study, we recommend to validate the findings for safety and efficacy in future through human prospective randomized controlled clinical trials.
Fulltext Dose-response relationship of photobiomodulation therapy and oxidative stress markers in healing dynamics of diabetic neuropathic ulcers in Wistar rats

Karkada G, Maiya GA, Arany P, Kg MR, Adiga S, Kamath SU

J Diabetes Metab Disord, 2023 Jun;22(1):393-400.
PMID: 37255770 DOI: 10.1007/s40200-022-01157-2

PURPOSE: Diabetic foot ulcers are reported to be the most expensive complications of diabetes, with high morbidity and mortality rates. If the necessary care is not provided for the wound to heal, the individual may end up amputating the affected feet. Photobiomodulation therapy is a promising non-pharmacological treatment option for wound healing. The objective of the present study is to establish a dose-response relationship between photobiomodulation therapy and oxidative stress markers in the healing dynamics of diabetic neuropathic ulcers in Wistar rats.
METHODOLOGY: Diabetic neuropathy was induced in 126 Albino Wistar rats. An excisional wound of an area of 2cm2 was made on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12, and 15 J/cm2 of wavelengths 655 and 808 nm was irradiated. The control group animals were kept un-irradiated. The outcome measures were assessed during wound healing's inflammatory, proliferative and remodelling phases.
RESULTS: In the experimental group, animals treated with photobiomodulation therapy at doses of 4, 6, and 8 J/cm2 showed better wound healing dynamics. Photobiomodulation therapy modulated the reactive oxygen species and antioxidant levels, thereby improving the oxidative status of the wound.
CONCLUSION: Photobiomodulation therapy of dosages 4, 6, and 8 J/cm2 is effective and is a promising adjuvant modality in treating diabetic neuropathic ulcers. There was a strong dose-response relationship in the experimental groups treated with 4, 6 and 8 J/ cm2.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-022-01157-2.