Therapeutic activity of green synthesized selenium nanoparticles from turmeric against cisplatin-induced oxido-inflammatory stress and cell death in mice kidney

Abstract

Cisplatin (CDDP) is a commonly prescribed chemotherapeutic agent; however, its associated nephrotoxicity limits its clinical efficacy and sometimes requires discontinuation of its use. The existing study was designed to explore the reno-therapeutic efficacy of turmeric (Tur) alone or conjugated with selenium nanoparticles (Tur-SeNPs) against CDDP-mediated renal impairment in mice and the mechanisms underlying this effect. Mice were orally treated with Tur extract (200 mg/kg) or Tur-SeNPs (0.5 mg/kg) for 7 days after administration of a single dose of CDDP (5 mg/kg, i.p.). N-acetyl cysteine NAC (100 mg/kg) was used as a standard antioxidant compound. The results revealed that Tur-SeNPs counteracted CDDP-mediated serious renal effects in treated mice. Compared with the controls, Tur or Tur-SeNPs therapy remarkably decreased the kidney index along with the serum levels of urea, creatinine, Kim-1, and NGAL of the CDDP-injected mice. Furthermore, Tur-SeNPs ameliorated the renal oxidant status of CDDP group demonstrated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and gene expression levels of HO-1. Noteworthy, lessening of renal inflammation was exerted by Tur-SeNPs via lessening of IL-6 and TNF-α besides down-regulation of NF-κB gene expression in mouse kidneys. Tur-SeNPs treatment also restored the renal histological features attained by CDDP challenge and hindered renal apoptosis through decreasing the Bax levels and increasing Bcl-2 levels. Altogether, these outcomes suggest that the administration of Tur conjugated with SeNPs is effective neoadjuvant chemotherapy to guard against the renal adverse effects that are associated with CDDP therapy.

Keywords: cisplatin; inflammation; nephrotoxicity; oxidative stress; selenium nanoparticles; turmeric extract.

Figure 1. Effects of orally administered turmeric (Tur), turmeric-loaded selenium nanoparticles (Tur-SeNPs), or N-acetyl cysteine (NAC) on renal function markers [(A) urea, (B) creatinine, (C) Kim-1, and (D) NGAL] and (E) kidney index in cisplatin (CDDP)-injected mice

Data are expressed as mean ± SD (n=7). a and b denote significant differences (P<0.05) compared with the untreated control and CDDP-treated groups, respectively.

Figure 2. Effects of orally administered turmeric (Tur), turmeric-loaded selenium nanoparticles (Tur-SeNPs), or N-acetyl cysteine (NAC) on the levels of non-enzymatic oxidative stress markers [(A) MDA, (B) NO, and (C) GSH] in the kidney of cisplatin (CDDP)-injected mice

Data are expressed as mean ± SD (n=7). a and b denote significant differences (P<0.05) compared with the untreated control and CDDP-treated groups, respectively.

Figure 3. Effects of orally administered turmeric (Tur), turmeric-loaded selenium nanoparticles (Tur-SeNPs), or N-acetyl cysteine (NAC) on the antioxidant enzymatic activities of (A) SOD, (B) CAT, (C) GPx, and (D) GR in the kidney of cisplatin (CDDP)-injected mice

Data are expressed as mean ± SD (n=7). a and b denote significant differences (P<0.05) compared with the untreated control and CDDP-treated groups, respectively.

Figure 4. Effects of orally administered turmeric (Tur), turmeric-loaded selenium nanoparticles (Tur-SeNPs), or N-acetyl cysteine (NAC) on the mRNA gene expression of hemeoxygenase (HO-1) in the kidney of cisplatin (CDDP)-injected mice

Data are expressed as mean ± SD (n=3 in duplicate). The mRNA levels were quantified with GAPDH as an internal control. a and b denote significant differences (P<0.05) compared with the untreated control and CDDP-treated groups, respectively.

Figure 5. Effects of orally administered turmeric (Tur), turmeric-loaded selenium nanoparticles (Tur-SeNPs), or N-acetyl cysteine (NAC) on the renal levels of (A) IL-6 and (B) TNF-α as well as (C) the mRNA gene expression of nuclear factor kappa-B (NF-κB) in the kidney of cisplatin (CDDP)-injected mice

Data are expressed as mean ± SD (n=7). The mRNA levels for NF-κB were quantified with GAPDH as an internal control. a and b denote significant differences (P<0.05) compared with the untreated control and CDDP-treated groups, respectively.

Figure 6. Effects of orally administered turmeric (Tur), turmeric-loaded selenium nanoparticles (Tur-SeNPs), or N-acetyl cysteine (NAC) on the levels of renal apoptotic markers [(A) Bcl-2 and (B) Bax] in cisplatin (CDDP)-injected mice

Data are expressed as mean ± SD (n=7). a and b denote significant differences (P<0.05) compared with the untreated control and CDDP-treated groups, respectively.

Figure 7. Effects of orally administered turmeric (Tur), turmeric-loaded selenium nanoparticles (Tur-SeNPs), or N-acetyl cysteine (NAC) on the renal histomorphological features of cisplatin (CDDP)-injected mice

(A) Photomicrograph of the renal tissue of the control group showing healthy kidney structure. (B) Photomicrograph of the renal tissue of mice treated with cisplatin (CDDP) showing shrunken glomeruli (yellow stars), cellular degeneration (white arrows), necrotic tubules (white stars), apoptosis (green arrows), and dilated tubules (blue arrows). (C) Photomicrograph of the renal tissue of CDDP-injected mice treated with turmeric (Tur) showing normal kidney structure. (D) Photomicrograph of the renal tissue of CDDP-injected mice treated with Tur-SeNPs showing damaged glomeruli (red stars) and hemorrhage (blue stars). (E) Photomicrograph of the renal tissue of CDDP-injected mice treated with NAC showing shrunken glomeruli (yellow stars), cellular degeneration (white arrows), apoptosis (green arrows), and inflammatory cell infiltration (orange arrows). Sections were stained with hematoxylin and eosin (× 400; scale bar = 100 µm).