S-Allylcysteine (SAC) Exerts Renoprotective Effects via Regulation of TGF- β1/Smad3 Pathway Mediated Matrix Remodeling in Chronic Renal Failure

Abstract

<P>Background: S-Allylcysteine (SAC), an organosulfur phytochemical sourced from aged garlic extract, is well known for its varied biomedical applications, such as anti-oxidant, anti-inflammatory, and detoxification mechanisms. Despite this, the scientific findings on the defensive impact of SAC against kidney failure (KF) are still unclear. Therefore, in the current investigation, the animal model of KF was induced by adenine in Wistar rats, and the animals were divided into four groups as control, KF induction using adenine, SAC treated KF rats for an experimental duration of 8 weeks. <P> Methods: KF progression was assessed by various serum and tissue markers, and the results demonstrated that the renal functions’ markers, KIM-1 (kidney injury molecule-1), cystatin, NGAL (neutrophil gelatinase-associated lipocalin), were found increased in adenine-treated rats compared to control. In addition, the inflammatory markers, matrix proteins, and fibrosis signatures explicated by RT-PCR, ELISA demonstrated a profound increase. On the other hand, rats received SAC mitigated KF considerably (p < 0.001) with restored cellular functions. Besides, SAC pre-treatment abrogated the cytokines and pro-inflammatory signals (COX-2 and PGE2) in a dose-dependent manner. <P> Conclusion: Furthermore, the fibrosis signaling markers mediators, such as SMAD-2,-3 were increased with associated matrix proteins. Thus, the present study substantiated that SAC possesses a significant renoprotective effect that might have been demonstrated by the inhibition of the TGF-&#946;1/Smad3 signaling pathway.</P>