Ginger (Zingiber officinale roscoe) extract could upregulate the renal expression of NRF2 and TNFα and prevents ethanol-induced toxicity in rat kidney

Abstract

Objective: Ginger has protective effects on the kidney, however the molecular mechanism of this effect has not yet been fully elucidated. Therefore, this work studied molecular mechanisms of ginger effects on ethanol-induced kidney injury.

Materials and methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups: control, ginger (1 g/kg/day ginger extract by oral gavage), ethanol (4 g/kg/day ethanol by oral gavage) and ginger-ethanol group and treated daily for 28 days. Kidney function, expression of nuclear factor erythroid 2-related factor 2 (NRF2) and tumor necrosis factor (TNF)-α genes and oxidative stress parameters in kidney tissue, were evaluated. Total phenolic content (TPC) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of ginger extract were also evaluated.

Results: Hydroethanolic extract of ginger showed a good level of DPPH scavenging activity and TPC. In the ethanol group, serum level of urea, creatinine and uric acid and the expression of NRF2 and TNF-α significantly increased compared to control group, while co-treatment with ginger in ginger+ethanol group significantly ameliorated them compared to the ethanol group. Ethanol exposure significantly reduced the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) compared to the control values ,while the level of malondialdehyde (MDA) significantly increased. Ginger significantly ameliorated the level of MDA and activity of SOD, GPx and CAT in the ginger-ethanol group compared to the ethanol group.

Conclusion: The results showed that ginger's protective effects against ethanol renotoxicity were mediated via enhancing the NRF2 and TNF-α expression.

Keywords: Ethanol; Ginger; Kidney; NRF2; Oxidative stress; TNF-α.

Figure 1

DPPH radical scavenging activity of extract of ginger

Figure 2

Comparison of the expression of NRF2 (A) and TNFα (B) among control and treated groups (n=6). Data are expressed as mean±SEM

Figure 3

Comparison of SOD (superoxide dismutase. A), CAT (catalase, B), TAC (total antioxidant capacity, C), MDA (Malondialdehyde, D) and GPx (glutathione peroxidase, E) among different groups (n=6). Data are expressed as mean±SEM

Figure 4

Histological finding of the rat kidney sections in the studied groups (×40). Light microscopic examination of kidney sections from control (A) and ginger (B) groups showed normal arrangement of glomerulus and no congestion in glomerular capillaries and medullary vessels. Evaluation of kidney sections from the ethanol group (C) showed that ethanol induced injury in the kidney which is characterized by abnormal glomerulus and congestion in glomerular capillaries, while co-treatment with ginger in animals treated with ethanol, improved these injuries (D)