TLR4‐IN‐C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis

Document Type : Original Article


1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

2 Department of Pharmacology, Faculty of Pharmacy, Horus University, Egypt


Objective(s): Acute kidney injury (AKI) is a major component of isoproterenol (ISO) induced cardiorenal syndrome. In this study, we investigated the effect of TLR4‐IN‐C34 as a toll-like receptor (TLR)-4 inhibitor on ameliorating ISO-induced AKI and the possible molecular underlying pathways. 
Materials and Methods: The study included 4 groups: control group, ISO group (rats received 100 mg/kg ISO in 2 doses 24 hr apart, SC), ISO+C341 and ISO+C343 groups (rats received 1 or 3 mg/kg TLR4‐IN‐C34 respectively twice one hour before each ISO injection, IP). 
Results: Obtained results showed that TLR4‐IN‐C34 injection prior to ISO decreased serum creatinine level (P<0.05). Renal tissue histopathologic changes were markedly decreased by TLR4‐IN‐C34. Renal relative expression of MAPK and MyD88 mRNA decreased significantly in both ISO+C341 and ISO+C343 groups compared with the ISO group (P<0.05). Furthermore, TLR-IN-C34 lowered the inflammatory cytokines IL-8, IL-1β, and IL-12 renal levels (P<0.05). Immunostained kidney sections showed a marked decrease in NF-κb positive cells in addition to the apoptotic marker Bax (P<0.05) by the two tested doses of TLR4‐IN‐C34. On the other hand, the expression of the antiapoptotic marker Bcl-2 by renal cells was markedly increased. 
Conclusion: It can be concluded that TLR4-IN-C34 ameliorates ISO-induced AKI through anti-inflammatory anti-apoptotic effects and modulation of TLR4 signaling pathways.


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