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

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.