Prednisolone is a glucocorticoid with anti-inflammatory and immunomodulatory effects. Prednisolone crosses the cell membrane and binds to cytoplasmic glucocorticoid receptors. This binding causes the receptor to dissociate from heat shock protein 90 and translocate into the nucleus. By binding to glucocorticoid response elements, Prednisolone promotes anti-inflammatory gene transcription. Prednisolone inhibits the activation of inflammatory transcription factors such as NF-κB. This reduces the release of inflammatory mediators including prostaglandins, leukotrienes, and cytokines. Prednisolone also suppresses inflammatory processes such as capillary dilation, leukocyte migration, and phagocytosis. Prednisolone can be used in studies related to rheumatoid arthritis, COVID-19, autoimmune diseases, and acute leukemia[1-4].
In vitro, treatment of CCRF-CEM cells with 700µM Prednisolone for 24-48 hours decreased MDR1 protein expression[5]. Treatment of pluripotent stem cell-derived skeletal muscle myogenic cultures with 10µM Prednisolone for 7 days promoted myofiber maturation[6]. Treatment of CCRF-CEM cells with 700µM Prednisolone for 12-48 hours time-dependently induced cell apoptosis[7].
In vivo, mdx mice received subcutaneous neck implantation of slow-release pellets delivering 0.8-1.3mg/kg Prednisolone for 60 consecutive days. Prednisolone reduced tibial ultimate load, decreased cortical bone cross-sectional area, and reduced cortical thickness[8]. KM mice received 15mg/kg Prednisolone intragastrically every other day for 2 consecutive weeks. Prednisolone narrowed the tibial growth plate, reduced trabecular bone volume, thinned cortical bone, and increased the number of TRAP-positive osteoclasts on the trabecular bone surface[9]. During the establishment of a contact hypersensitivity model by applying 0.15% 2,4-dinitrofluorobenzene (DNFB) in acetone-olive oil solution (3:1) to ears weekly for a total of 5 applications, BALB/c mice received topical application of 10μL 0.1% or 0.3% Prednisolone to both sides of both ears twice per week for 4 consecutive weeks. Prednisolone inhibited DNFB-induced ear swelling, suppressed the increase in transepidermal water loss, and inhibited the absolute increases in ear skin triglycerides and cholesterol as well as the total lipid increase[10].
References:
[1] Tfelt-Hansen P, Daugaard D, Lassen LH, et al. Prednisolone reduces nitric oxide-induced migraine. Eur J Neurol. 2009 Oct;16(10):1106-11.
[2] Derendorf H, Rohdewald P, Möllmann H, et al. Pharmacokinetics of prednisolone after high doses of prednisolone hemisuccinate. Biopharm Drug Dispos. 1985 Oct-Dec;6(4):423-32.
[3] Jusko WJ, Rose JQ. Monitoring prednisone and prednisolone. Ther Drug Monit. 1980;2(2):169-76.
[4] Gilchrist FJ, Ahmad AN, Batchelor HK, et al. A review of prednisolone prescribing for children with acute asthma in the UK. J Asthma. 2016 Aug;53(6):563-6.
[5] Talebi M, Bahar Aghdam S, Azimi A, et al. Regulatory effect of resveratrol and prednisolone on MDR1 protein expression in acute lymphoblastic leukemia cell line (CCRF-CEM). Asian Pac J Cancer Prev. 2019 Apr;20(4):1171-1176.
[6] Al Tanoury Z, Zimmerman JF, Rao J, et al. Prednisolone rescues Duchenne muscular dystrophy phenotypes in human pluripotent stem cell-derived skeletal muscle in vitro. PNAS. 2021 Jul 6;118(28):e2022960118.
[7] Ghasemi A, Khanzadeh T, Zadi Heydarabad M, et al. Evaluation of BAX and BCL-2 gene expression and apoptosis induction in acute lymphoblastic leukemia cell line CCRF-CEM after high-dose prednisolone treatment. Asian Pac J Cancer Prev. 2018;19(8):2319-2323.
[8] Novotny SA, Warren GL, Lin AS, et al. Prednisolone treatment and restricted physical activity further compromise bone of mdx mice. J Musculoskelet Neuronal Interact. 2012 Mar;12(1):16-23.
[9] Sun B, Sun J, Han X, et al. Immunolocalization of MMP 2, 9 and 13 in prednisolone induced osteoporosis in mice. Histol Histopathol. 2016;31(6):647-656.
[10] Ueda Y, Sone T, Inagaki N, et al. Effects of Prednisolone on the Cutaneous Reaction and Skin Barrier Function in Mice Treated with a Hapten. Biol Pharm Bull. 2003 May;26(5):618-621.