Amelioration of Drug-Induced Nephrotoxicity with Ganglioside Liposomes

Background: The commonly prescribed drugs e.g. antibiotics, NSAIDs, diuretics, antihypertensives, and anticancer drugs are often associated with nephrotoxicity as their side effects. They cause acute kidney injury. The common mechanism of nephrotoxicity is via induction of reactive oxygen species (ROS) downstream which accumulate in the cells and activate various signaling pathways leading to renal tubular cell death. Ganglioside GM 1 nanoliposomes (NLGM1) have previously been shown to be effective infighting oxidative stress via the Nrf2-Keap1 signaling pathway. In this research we aim to investigate the utility of NLGM1 in overcoming nephrotoxicity. Methods: NLGM1 were prepared using phosphatidylcholine cholesterol, and monosialoganglioside using lipid film hydration method. In a detailed in vitro investigation, assays such as cell viability assay and ELISA assay for the sensitive biomarker of kidney injury viz. Kidney Injury marker-1 (KIM-1) and Heme Oxygenase (HO) were carried out on HK-2 cells from the proximal tubule using commercially available kits. Results: Dose-dependent HK-2 cell killing was observed in all drugs tested. Cell killing was found to be reversed to more than 90% viability in presence of NLGM1 in all concentrations tested for all drugs (p< 0.05). KIM-1 was found to be significantly low (p< 0.05) in presence of NLGM1 with nephrotoxic drugs compared to nephrotoxic drugs alone. HO concentrations in presence of NLGM1 with nephrotoxic drugs were significantly higher (p< 0.005) compared to nephrotoxic drugs alone (Fig. 1). Conclusion: Utility of NLGM1 liposomes in reversing the nephrotoxic drug induced cell killing and reduction in KIM-1levels and higher HO-1 levels was established in the various in vitro assays we performed. In the future, we intend to execute in vivo assays, e.g., KIM-1 ELISA, histopathology etc., in rats to establish the efficacy of NLGM1 liposomes further.Figure 1: HO analysis in presence of nephrotoxic agent (Vancomycin) with and without NLGM1