International immunopharmacology · 2025
Immune regulation of TLR4/MYD88/ NF-κB/AP1/IL-6 pathway and modulation of aldosterone/PPARα receptors by eplerenone and fenofibrate in ovarian ischemia reperfusion induced injury.
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Refaie Marwa Monier Mahmoud, Abdel-Hakeem Elshymaa A, Shehata Sayed, Elsaghir Shereen Mohammed Mohammed, Mokhemer Sahar Ahmed, Ahmed Nagwa Zenhom Mustafa, Elsayed Samar Hisham, Mageed Aya Aly Ashraf Abdel, Mohamed Heba Reda, Shawky Heba A, Ali Doaa Mohamed Elroby
Аннотация
BACKGROUND: The immune system is deeply involved in the pathogenesis of different gynecological disorders including ovarian torsion that commonly occurs during surgical manipulation or within ovarian masses, affecting not only the ovaries, but it has remote effect on different organs particularly cardiac tissue. Early intervention and proper medical treatment are so important to preserve the ovaries and prevent distant organ damage. Accordingly, the aim of this work was to evaluate the possible ameliorative role of eplerenone (EPL) or fenofibrate (FEN) on ovarian and cardiac affection in an experimental model of ovarian ischemia/reperfusion (OIR).
METHOD: Fifty female Wistar albino rats were divided into five groups (n = 10); control, OIR induced group, OIR plus EPL (100 mg/kg), OIR plus FEN (300 mg/kg), OIR plus EPL (100 mg/kg) plus FEN (300 mg/kg).
RESULTS: OIR could induce ovarian injury with remote cardiac damage. Data of current study revealed significant increases of the cardiac enzymes, and malondialdehyde (MDA) levels but decreases of total anti-oxidant capacity (TAC) and reduced glutathione (GSH) levels. Moreover, there were increases in toll like receptor 4 (TLR4), myeloid differentiation primary response 88 (MYD88), activation protein 1 (AP1), interleukin 6 (IL-6), nuclear factor kappa b (NF-κB) and cleaved caspase-3 with abnormal histological features. However, EPL or FEN co-administration alone or in combination reversed OIR damaging effects by antagonizing aldosterone action by EPL, anti-inflammatory, anti-oxidant, and anti-apoptotic features with modulation of peroxisome proliferator activated receptor alpha (PPARα) by FEN and TLR4/MYD88/ NF-κB/AP1/IL-6 pathway. Interestingly, co-administration of both drugs showed more improvement than giving each one alone.
CONCLUSION: EPL and/or FEN had ameliorative properties against OIR induced harmful effects.
METHOD: Fifty female Wistar albino rats were divided into five groups (n = 10); control, OIR induced group, OIR plus EPL (100 mg/kg), OIR plus FEN (300 mg/kg), OIR plus EPL (100 mg/kg) plus FEN (300 mg/kg).
RESULTS: OIR could induce ovarian injury with remote cardiac damage. Data of current study revealed significant increases of the cardiac enzymes, and malondialdehyde (MDA) levels but decreases of total anti-oxidant capacity (TAC) and reduced glutathione (GSH) levels. Moreover, there were increases in toll like receptor 4 (TLR4), myeloid differentiation primary response 88 (MYD88), activation protein 1 (AP1), interleukin 6 (IL-6), nuclear factor kappa b (NF-κB) and cleaved caspase-3 with abnormal histological features. However, EPL or FEN co-administration alone or in combination reversed OIR damaging effects by antagonizing aldosterone action by EPL, anti-inflammatory, anti-oxidant, and anti-apoptotic features with modulation of peroxisome proliferator activated receptor alpha (PPARα) by FEN and TLR4/MYD88/ NF-κB/AP1/IL-6 pathway. Interestingly, co-administration of both drugs showed more improvement than giving each one alone.
CONCLUSION: EPL and/or FEN had ameliorative properties against OIR induced harmful effects.