Vitamin C attenuates vancomycin induced nephrotoxicity through the reduction of oxidative stress and inflammation in HK-2 cells.

Abstract

Oxidative stress is one of the possible mechanisms in vancomycin (VCM) induced nephrotoxicity. Some studies suggested that high dose Vitamin C (VC) has protective effect against the nephrotoxicity in mice, but the underlying molecular mechanism is not mentioned. We investigated the potential targets of high dose VC against oxidative stress and inflammation induced by VCM in renal tubular epithelial cells. We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2). VCM added to HK-2 cells caused an increase of cell death, oxidative stress and expression of inflammatory cytokines. Co-treatment with 0.5 and 1 mM VC attenuated 4-8 mM VCM induced cell death and increased the cell viability to 58-90%. VC significantly decreased lipid peroxidation and increased superoxide dismutase activity. The upregulations of NF-κB, TNF-α and IL-6 in HK-2 cells under 4 mM VCM were also reversed by 0.5 mM VC through the inhibition of oxidative stress. This study showed for the first time that VC can attenuate the VCM induced nephrotoxicity by decreasing lipid peroxidation and expression of inflammatory cytokines, and increasing superoxide dismutase 2 (SOD2) activity, this effect may relate to the regulation of ROS/NF-κB pathway.