Pharmacological inhibition of TLR4/NF‐κB with TLR4‐IN‐C34 attenuated microcystin‐leucine arginine toxicity in bovine Sertoli cells. Issue 6 (22nd January 2019)

• Record Type: Journal Article
• Authors: Adegoke, Elikanah Olusayo; Adeniran, Samson Olugbenga; Zeng, Yue; Wang, Xue; Wang, Hao; Wang, Chen; Zhang, Han; Zheng, Peng; Zhang, Guixue
• Is Part Of: Journal of applied toxicology. Volume 39:Issue 6(2019)
• Page Start: 832
• Page End: 843
• Publication Date: 2019-01-22
• Subjects: apoptosis -- blood‐testis barrier -- bovine -- microcystin‐LR -- mitochondrion -- mitophagy; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3771
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: This study investigated the pharmacological inhibition of the toll‐like receptor 4 (TLR4) genes as a measure to attenuate microcystin‐LR (MC‐LR) reproductive toxicity. Bovine Sertoli cells were pretreated with TLR4‐IN‐C34 (C34) for 1 hour. Thereafter the pretreated and non‐pretreated Sertoli cells were cultured in medium containing 10% heat‐activated fetal bovine serum + 80 μg/L MC‐LR for 24 hours to assess the ability of TLR4‐IN‐C34 to attenuate the toxic effects of MC‐LR. The results showed that TLR4‐IN‐C34 inhibited MC‐LR‐induced mitochondria membrane damage, mitophagy and downregulation of blood‐testis barrier constituent proteins via TLR4/nuclear factor‐kappaB and mitochondria‐mediated apoptosis signaling pathway blockage. The downregulation of the mitochondria electron transport chain, energy production and DNA replication related genes (mt‐ND2, COX‐1, COX‐2, ACAT, mtTFA) and upregulation of inflammatory cytokines (interleukin [IL]‐6, tumor necrosis factor‐α, IL‐1β, interferon‐γ, IL‐4, IL‐10, IL‐13 and transforming growth factor β1) were modulated by TLR4‐IN‐C34. Taken together, we conclude that TLR4‐IN‐C34 inhibits MC‐LR‐related disruption of mitochondria membrane, mitophagy and downregulation of blood‐testis barrier proteins of the bovine Sertoli cell via cytochrome c release and TLR4 signaling blockage. Abstract : Bovine Sertoli cells were pretreated with 10 μM TLR4‐IN‐C34 and thereafter exposed to 80 μg/L microcystin ‐leucine arginine (MC‐LR) for 24 h to assess its ameliorative effects. The results showed that TLR4‐IN‐C34 inhibited MC‐LR induced mitochondria membrane damage, mitophagy and downregulation of blood‐testis barrier constituent proteins via TLR4/NF‐kB and mitochondria mediated‐ apoptosis signaling pathways blockage. The mitochondria electron transport chain, energy production, DNA replication and inflammatory cytokines were also modulated by TLR4‐IN‐C34.