Chitosan nanoencapsulation of Turbinaria triquetra metabolites in the management of podocyturia in nephrotoxic rats

Abstract

Cisplatin is a chemotherapeutic drug, which exhibits undesirable side effects. Chitosan nanoparticles are promising for drug delivery. The aim of this study was to determine the effect of the brown alga Turbinaria triquetra ethyl acetate fraction and polysaccharides, either loaded on chitosan nanoparticles or free, against podocyturia and cisplatin nephrotoxicity in rats. Sixty-six male rats were distributed into 11 equal groups: untreated control, chitosan (CSNPs), ethyl acetate fraction (EAE), polysaccharide (PS), EAE loaded on chitosan nanoparticles (EAE-CSNPs), PS loaded on chitosan nanoparticles (PS-CSNPs), Cisplatin or cis-diamminedichloroplatinum(II) (CDDP), CDDP + EAE, CDDP + PS, CDDP + EAE-CSNPs, and CDDP + PS-CSNPs. Serum urea, creatinine, creatinine clearance, renal malondialdehyde, nitric oxide, paraoxonase 1, renal nephrin, and podocin, and their renal mRNA gene expressions, as well as urinary nephrin and podocin were determined. The results indicated that the ethyl acetate fraction and polysaccharides, either free or loaded, efficiently attenuated podocyturia and cisplatin nephrotoxicity compared to the Cis group. However, the improvement was higher in the nephrotoxic groups treated with EAE-CSNPs and PS-CSNPs. The current study revealed that chitosan nanoencapsulation showed ameliorative effects against podocyturia and cisplatin nephrotoxicity in rats compared to free extracts, offering a new therapeutic strategy for attenuating podocyturia and CDDP-induced nephrotoxicity.

Keywords: Turbinaria Triquetra; Brown alga; Chitosan nanoparticles; Cisplatin; Nephrotoxicity; Podocyturia; Polysaccharide.

Fig. 1

Gallic acid standard curve.

Fig. 2

TEM micrographs of (A) CSNPs, (B) EAE-CSNPs and (C) PS-CSNPs.

Fig. 3

Mean value of (A) Serum urea (mg/dl), (B) Serum creatinine (mg/dl) and (C) Creatinine clearance (ml/min/kg bw) in different groups. There was no significance difference between the six first groups (control-PS-CSNPs). There was significance difference between Cis group and Cis + EAE and Cis + PS (p < 0.05*), while there was high significance between Cis group and Cis + EAE-CSNPs and Cis + PS-CSNPs (p < 0.001*). Error bars represent standard error.

Fig. 4

Mean value of (A) Renal MDA (nmol/g tissue), (B) Renal NO (nmol/g tissue) and (C) Renal PON 1(u/g tissue) in different groups. There was no significance difference between the six first groups (control-PS-CSNPs). There was significance difference between Cis group and Cis + EAE and Cis + PS (p < 0.05*), while there was high significance between Cis group and Cis + EAE-CSNPs and Cis + PS-CSNPs (p < 0.001*). Error bars represent standard error.

Fig. 5

Mean value of (A) Renal nephrin (ng/ml), (B) Renal podocin (ng/ml), (C) Relative expression of renal nephrin mRNA and (D) Relative expression of renal podocin mRNA in different studied groups. There was no significance difference between the six first groups (control-PS-CSNPs). There was significance difference between Cis group and Cis + EAE and Cis + PS (p < 0.05*), while there was high significance between Cis group and Cis + EAE-CSNPs and Cis + PS-CSNPs (p < 0.001*). Error bars represent standard error.

Fig. 6

Mean value of (A) Urinary nephrin (ng/ml) and (B) Urinary podocin (ng/ml) in different studied groups. There was no significance difference between the six first groups (control-PS-CSNPs). There was significance difference between Cis group and Cis + EAE and Cis + PS (p < 0.05*), while there was high significance between Cis group and Cis + EAE-CSNPs and Cis + PS-CSNPs (p < 0.001*). Error bars represent standard error.

Fig. 7

A photomicrograph of H&E stained section from rat kidney of (A) Control group, (B) Carrier group, (C) EAE group, (D) PS group, (E) EAE-CSNPs group and (F) PS-CSNPs group showed normal structure of the glomerulus (G), urinary space (Us) and tubules (T) (Magnification x 200).

Fig. 8

A photomicrograph of H&E stained section from rat kidney of (A) Cis group showed shrunken glomeruli (G) with dilated urinary space (Us), tubular epithelial cell degeneration (T), necrosis associated with interstitial inflammatory cells and interstitial hemorrhage, (B) Cis + EAE group, (C) Cis + PS group showed moderate ameliorative effect with slight atrophy of glomeruli (G), mild dilated urinary space (Us) and mild necrosis with mild inflammatory cells, (D) Cis + EAE-CSNPs group, (E) Cis + PS-CSNPs group showed marked ameliorative effect with slight atrophy of glomeruli (G) and mild dilated urinary space (Us) (Magnification x 200).