Platelet rich plasma mitigates silver nanoparticles induced - pulmonary fibrosis in Wister rats via CASPASE -3 &TWIST-1genes downregulation

Abstract

Abstract Silver nanoparticles (AgNPs) are widely known for their anticancer, anti-inflammatory, and antimicrobial uses. Still, hazardous usage of AgNPs can damage various tissues, including the lung and is considered as environmental toxin. The ability of platelet rich plasma (PRP) to lessen the pulmonary damage caused by AgNps is not widely recognized. The aim of this study was to evaluate the efficacy of PRP, a natural yet harmless biological substance, in reducing lung fibrosis and damage caused by AgNps in rats. Forty-eight adults male Wistar albino rats were divided into six groups; Group 1, donors for PRP; Group 2, control rats; Group 3, received AgNPs (10 mg kg-1 of body weight (BWt) once daily by intraperitoneal (i.p.) injection for4 successive weeks; Group 4, received AgNPs +PRP (0.5ml kg-1. BWt i.p.) two days / week after AgNPs for for 3 weeks); Group 5, AgNPs+ dexamethasone (0.5 mg kg -1 i.p) for for 4 weeks after AgNPs treatment; Group 6, recovery group received Ag-NPs and then left for another 4 weeks without treatment. This study included the assessment of; BWt, hydroxyproline level in lung tissue. In addition, Caspase-3, and TWIST -1 gene expression in lung tissue as markers for apoptosis and fibrosis, respectively, was assessed using Rt-PCR. Also, histological (H/E &Siris red staining) and immunohistochemical studies were conducted to detect the expression of inducible nitric oxide synthase (iNOS) and cluster of differentiation 68 (CD68) in lung tissue associated with histomorphometry studies. Significant increase in BWt was noted in AgNPs group when compared to AgNPs +PRP group (p<0.001). Hydroxyproline levels were markedly increased by AgNPs and decreased after PRP treatment (p<0.001). Caspase-3 and TWIST-1 genes were up-regulated in AgNPs group and significantly downregulated in AgNPs+PRP group. AgNPs induced deleterious changes in the lung tissues, including thickening of the interalveolar septa, collapse of the lung alveoli, diffuse lymphocytic infiltration and pulmonary fibrosis. This was also associated with increased alveolar macrophage CD68 expression and iNOS positivity in the cells lining the alveoli compared to AgNPs group. Treatment with PRP markedly improved histopathological and immunohistochemical picture. Surprisingly, the effect of PRP was comparable to dexamethasone. The herein study showed that treatment with PRP is a promising, natural, safe, and effective treatment against AgNPs induced lung fibrosis and injury by playing anti-apoptotic, anti-fibrotic, anti-inflammatory, and anti-oxidative stress roles.