Medhat Taha; Mohie Mahmoud Ibrahim; Sara T. Elazab; Alaa. M. Badawy; Ramy A. Abdelsalam; Abdullah A. Saati; Naeem F. Qusty; Omar Babateen; Omer Abdelbagi & Hendawy, M.

One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.

KEY WORDS: Diacerein; Renal ischemia; Dendritic cells; Oxidative stress; Inflammation; Apoptosis.

TAHA, M.; IBRAHIM, M. M.; ELAZAB, S. T.; BADAWY, A. M.; ABDELSALAM, R. A.; SAATI, A. A.; QUSTY, N. F.; BABATEEN, O.; ABDELBAGI, O. & HENDAWY, M. Diacerein mitigates renal ischemia/reperfusion injury via inhibition of renal inflammation, dendritic cells maturation and apoptosis: The role of TLR4/NF-κB/NLRP3/IL-1β signaling pathway. Int. J. Morphol., 41(2):625-633, 2023.