Lixisenatide protects doxorubicin-induced renal fibrosis by activating wNF-κB/TNF-α and TGF-β/Smad pathways

N.-F. Guo, Y.-J. Cao, X. Chen, Y. Zhang, Y.-P. Fan, J. Liu, X.-L. Chen

Department of Nephrology, the Affiliated Hospital of Nantong University, Nantong, China. chenxl8448@sina.com

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• Pharmacology

OBJECTIVE: The aim of this study was to investigate whether Lixisenatide, NF-kB/TNF-α, and TGF-β/Smad pathways exert clear regulatory roles in doxorubicin-induced renal fibrosis in rats, and to explore the possible underlying mechanism.
MATERIALS AND METHODS: 30 rats were randomly assigned into the sham group, the Doxorubicin (DOX) group and the Lixisenatide group, 10 in each group. Eight weeks after the specific animal procedure, serum and kidney samples of rats were collected. The serum levels of Cr and BUN were detected using relative commercial kits. The activities of malondialdehyde (MDA), total antioxidant capacity (T-AOC), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD) in kidney homogenate were accessed using commercial kits. Meanwhile, pathological lesions in kidney tissues were evaluated by HE staining, immune-histochemical staining and TUNEL assay, respectively. Also, the protein levels of relative genes in NF-kB/TNF-α, and TGF-β/Smad pathways in rat kidneys were determined by immune-histochemical staining and Western blot, respectively.
RESULTS: Rats in the Lixisenatide group showed significantly lower levels of Cr and BUN. Activities of T-AOC, CAT, GSH, and SOD in the Lixisenatide group were significantly higher, whereas MDA activity was significantly lower than in the DOX group. Lixisenatide treatment remarkably alleviated DOX-induced pathological lesions and cell apoptosis in kidneys. Furthermore, the protein levels of relative genes in NF-kB/TNF-α and TGF-β/Smad pathways in rat kidneys were significantly downregulated in the Lixisenatide group when compared with the DOX group.
CONCLUSIONS: Lixisenatide protects doxorubicin-induced renal fibrosis in rats by inhibiting NF-κB/TNF-α and TGF-β/Smad pathways.

This article has been retracted. The Publisher apologizes for any inconvenience this may cause. Retraction note in: Eur Rev Med Pharmacol Sci 2023; 27 (14): 6472-6472.

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