Gingerol Fraction from Zingiber officinale Protects Against Gentamicin-

26 Nephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces 27 renal damage by overproduction of reactive oxygen species and inflammation in 28 proximal tubular cells. Phenolic compounds from ginger, called gingerols, have 29 demonstrated to have antioxidant and anti-inflammatory effects. We investigated if the 30 oral treatment with an enriched solution of gingerols (GF) would promote a 31 nephroprotective effect using an animal nephropathy-model. Six groups of male Wistar 32 rats were studied: 1) Control group (CT), 2) gingerol solution control (GF), 3) 33 gentamicin treatment (GM) 100 mg/kg i.p, 4-6) gentamicin plus GF at doses of 6.25, 34 12.5 and 25 mg/kg (GM+GF). Animals from the GM group had a significant decrease 35 in creatinine clearance and higher levels of urinary protein excretion. This was 36 associated with markers of oxidative stress and oxide nitric production. Also, there was 37 activation of the mRNA levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-2 and 38 INF-γ). The histopathological findings of tubular degeneration and inflammatory cell 39 infiltration reinforced GM-induced nephrotoxicity. All these alterations were attenuated 40 by previous oral treatment with GF. Animals from the GM+GF groups showed 41 amelioration in renal function parameters, reduced lipid peroxidation and nitrosative 42 stress, in addition to an increment in the levels of glutathione (GSH) and superoxide 43 dismutase (SOD) activity. Gingerols also promoted significant reduction in mRNA 44 transcription of TNF-α, IL-2 and INF-γ. These effects were dose-dependent. These 45 results demonstrated that GF promoted a nephroprotective effect on GM-mediated 46 nephropathy by oxidative stress, inflammatory process and renal dysfunction. 47 48 49