Unfractionated bone marrow cells attenuate paraquat-induced glomerular injury and acute renal failure by modulating the inflammatory response

Abstract

The aim of this study was to evaluate the efficacy of unfractionated bone marrow cells (BMCs) in attenuating acute kidney injury (AKI) induced by paraquat (PQ) in a mouse model. PQ (55 mg/kg BW) was intraperitoneally injected into C57BL/6 female mice to induce AKI, including renal function failure, glomerular damage and renal tubule injury. Glomerular podocytes were the first target damaged by PQ, which led to glomerular injury. Upon immunofluorescence staining, podocytes depletion was validated and accompanied by increased urinary podocin levels, measured on days 1 and 6. A total of 5.4 × 106 BMCs obtained from the same strain of male mice were injected into AKI mice through the tail vein at 3, 24, and 48 hours after PQ administration. As a result, renal function increased, tubular and glomerular injury were ameliorated, podocytes loss improved, and recipient mortality decreased. In addition, BMCs co-treatment decreased the extent of neutrophil infiltration and modulated the inflammatory response by shifting from pro-inflammatory Th1 to an anti-inflammatory Th2 profile, where IL-1β, TNF-α, IL-6 and IFN-γ levels declined and IL-10 and IL-4 levels increased. The present study provides a platform to investigate PQ-induced AKI and repeated BMCs injection represents an efficient therapeutic strategy.

Attenuation of Paraquat-Induced Nephrotoxicity and Dysfunction in Male Wistar Albino Rats

“…These two parameters are biomarkers of renal toxicity [33] and the increase indicate renal damage associated with increased urea production. This is in line with previous reports [34,35]. However, garlic supplementation showed the significant ameliorative potential to the abnormal urea and creatinine production as presented by rats in the garlic group.…”

Protective and anti-inflammatory effects of silymarin on paraquat-induced nephrotoxicity in rats

“…Urea and Cr are among the markers of renal toxicity workup (29). In this study, there is an increase in serum urea and Cr levels in group 2 (Table 1), which indicates the paraquat-induced renal damage; which was consistent with previous studies (27,29,30). In our study, administration of silymarin led to protect kidneys against paraquat toxicity and reduces serum urea and Cr levels ( Table 1).…”

“…Paraquat is secreted by proximal tubules before renal damage, but tubular damages happen with an increase in paraquat concentration. In paraquat-induced renal toxicity, primarily the glomerular coatings (podocytes) are damaged; then, tubular degeneration, and the formation of eosinophilic granular cytoplasm is happen in distal and proximal tubules (25)(26)(27).…”

Effect of curcumin on glycerol-induced acute kidney injury in rats

“…TNF-α also activates caspase-mediated apoptosis through activation of the death receptor pathway 55 . It was reported that TNF-α and IL-6 expression were significantly elevated in chronic renal failure patients 60 and rat AKI models using cisplatin and paraquat to induce AKI 61 , 62 . MCP-1 is a more recently studied renal biomarker which is expressed in injury and inflammation sites and directs the recruitment of macrophages, which bind to chemokine receptors to promote macrophage adhesion and chemotaxis 63 .…”