NAC attenuates adriamycin-induced nephrotic syndrome in rats through regulating TLR4 signaling pathway

H. Yao, Z.-Y. Cai, Z.-X. Sheng

Department of Renal Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. 471007299@qq.com

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• Pharmacology

OBJECTIVE: Nephrotic syndrome (NS) is a detrimental renal disease that affects a large population. It is suggested that Toll-like Receptor 4 (TLR4) signaling pathway plays an important role in NS. The aim of this study was to evaluate the immunosuppressive effect of N-acetylcysteine (NAC) in the treatment of NS elucidate its interaction with TLR4 pathway in a rat model.

MATERIALS AND METHODS: Rat NS model was constructed using the Bertain method by injecting adriamycin (4.5 mg/kg) intravenously at day 1, and injecting 2 mg/kg adriamycin (ADR) at day 7. NS rats were treatment with NAC of 150 mg/kg daily through gavage. Control rats received equivalent amounts of saline daily. Quantitative Real-time PCR was used to evaluate TLR4 expression in kidney tissues after treatments. Western blot analysis was used to evaluate NF-κBp65 expression. ELISA was used to evaluate the expression of immunological factors, including TNF-α, IL-6, and IL-1β.

RESULTS: Rat NS models demonstrated higher protein levels in urine, accompanied by an increased in the TLR4 level. After NAC treatment, TLR4 level was reduced. NAC treatment also attenuated the NF-κBp65 overexpression in NS rats. Concomitantly, TNF-α, IL-6, and IL-1β levels, which are indicators of immunological and informatory responses, were also decreased after NAC treatment.

CONCLUSIONS: NAC treatment ameliorated nephrotic syndrome in NS rat models by suppressing TLR4 signaling, as well as immunological and inflammatory responses.

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