Renoprotective Effect of Platelet-Rich Plasma on Cisplatin-Induced Nephrotoxicity in Rats

Abstract

Platelet-rich plasma (PRP) has grown as an attractive biologic instrument in regenerative medicine for its powerful healing properties. It is considered as a source of growth factors that may induce tissue repairing and improve fibrosis. This product has proven its efficacy in multiple studies, but its effect on cisplatin-induced nephrotoxicity has not yet been elucidated. The present investigation was performed to estimate the protective impact of platelet-rich plasma against cisplatin- (CP-) evoked nephrotoxicity in male rats. Nephrotoxicity was induced in male Wistar rats by right uninephrectomy followed by CP administration. Uninephrectomized rats were assigned into four groups: (1) control group, (2) PRP group, (3) CP group, and (4) CP + PRP group. PRP was administered by subcapsular renal injection. Renal function, inflammatory cytokines, and growth factor level as well as histopathological investigation were carried out. Treatment with PRP attenuated the severity of CP-induced nephrotoxicity as evidenced by suppressed creatinine, blood urea nitrogen (BUN), and N-acetyl glucosaminidase (NAG) levels. Moreover, PRP depressed intercellular adhesion molecule-1 (ICAM-1), kidney injury molecule-1 (KIM-1), caspase-3, and transforming growth factor-beta 1 (TGF-β1) levels, while enhanced the epidermal growth factor (EGF) level. These biochemical results were reinforced by the histopathological investigation, which revealed restoration of normal renal tissue architectures. These findings highlight evidence for the possible protective effects of PRP in a rat model of CP-induced nephrotoxicity, suggesting a new avenue for using PRP to improve the therapeutic index of cisplatin.

Figure 1

Box and whisker plots showing the effect of PRP administration on serum Cr, BUN, and NAG levels in CP nephrotoxic rats. (a) Creatinine level. (b) Blood urea nitrogen (BUN). (c) N-acetyl-glucosaminidase (NAG). Data are expressed as median and interquartile range. Boxes refer to the 25th (bottom) and 75th (up) percentiles, and the median is the horizontal line inside. PRP: platelet-rich plasma (2410 × 10³ platelets/μL); CP: cisplatin (10 mg/kg). Treatments with different letters are significantly different at p ≤ 0.05.

Figure 2

Box and whisker plots showing the effect of PRP administration on renal ICAM-1, KIM-1, and caspase-3 levels in CP nephrotoxic rats. (a) ICAM-1: intercellular adhesion molecule-1. (b) KIM-1: kidney injury molecule-1. (c) Caspase-3. Data are expressed as median and interquartile range. Boxes refer to the 25th (bottom) and 75th (up) percentiles, and the median is the horizontal line inside. PRP: platelet-rich plasma (2410 × 10³ platelets/μL); CP: cisplatin (10 mg/kg). Treatments with different letters are significantly different at p ≤ 0.05.

Figure 3

Box and whisker plots showing the effect of PRP administration on renal TGF-β1 and EGF levels in CP nephrotoxic rats. (a) TGF-β1: transforming growth factor-beta 1; EGF: epidermal growth factor. Data are expressed as median and interquartile range. Boxes refer to the 25th (bottom) and 75th (up) percentiles, and the median is the horizontal line inside. PRP: platelet-rich plasma (2410 × 10³ platelets/μL); CP: cisplatin (10 mg/kg). Treatments with different letters are significantly different at p ≤ 0.05.

Figure 4

Effect of PRP administration on renal histopathology in CP nephrotoxic rats. Photomicrographs of sections from rat renal tissues. (a) Control group rats received saline showing normal histomorphological architectures. (b) PRP group rats received 1 m PRP elicited no histologic modification. (c, d, e) CP group rats received CP (10 mg/kg) showing (c) necrotic and shrunken glomerular tufts (star), minute peritubular spindle cells (thin arrow) beside sloughed tubular epithelium (thick arrow). (d) Necrotic areas (thick arrow) beside mesangial proliferative glomerulonephritis (star) and numerous casts in injured renal tubule lumina (thin arrow). (e) Interstitial fibrous streaks in corticomedullary junctions (star). (f) CP + PRP group showing a few delicate tubular casts (arrow) within the apparently normal renal tissues. Hematoxylin and eosin staining. Scale bar = 50 μm.