Diallyl disulfide ameliorates kidney damage associated with polycystic ovary syndrome by targeting STAT1/ NF-κB and Nrf2/HO-1 signaling

Abstract

Diallyl disulfide (DADS), a significant bioactive component of garlic, has many advantageous biological purposes. It is unknown how DADS affects renal disorder in PCOS patients. In a rat model of PCOS, our study postulated that DADS would safeguard against renal dysfunction possibly by combating NF-κB and enhancing Nrf2 dependent mechanism. Female Wistar rats were randomly divided into 4 groups (n = 8); normal control, PCO induced by letrozole (LET) (1mg kg-1day-1, p.o.), protective group; DADS (50 mg kg-1 day-1, p.o.) + LET, and therapeutic group; LET followed by DADS treatment. DADS significantly reduced serum creatinine, urea, body weight, hyperinsulinemia, hyperglycemia, hyperandrogenism, and dyslipidemia. In addition, DADS obviously diminished PCOS-induced elevations in STAT1, NF-κB, TNFα, and IL6 and increased IL10. Moreover, DADS significantly reduced oxidative stress markers (MDA and NOX4) and increased SOD, GST, and PON1 in renal tissue. Furthermore, DADS positively regulated the Nrf2, HO-1, and NQO1 genes. DADS up-regulates Bcl2 expression in cortical glomerular capillaries and renal tubules and down regulates the expression of caspase-3. Our research revealed that DADS significantly ameliorated kidney dysfunction and renal injury associated with PCOS. The antioxidant, anti-inflammatory, and anti-apoptotic properties of DADS may signify a crucial part of its applications in therapy. DADS may be a probable therapy in PCOS to lessen the linked kidney damage through targeting STAT1/ NF-κB and Nrf2/HO-1 signaling.