title: Gingerol fraction from Zingiber officinale protects against gentamicin-induced nephrotoxicity.
abstract: Nephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal damage by overproduction of reactive oxygen species and inflammation in proximal tubular cells. Phenolic compounds from ginger, called gingerols, have been demonstrated to have antioxidant and anti-inflammatory effects. We investigated if oral treatment with an enriched solution of gingerols (GF) would promote a nephroprotective effect in an animal nephropathy model. The following six groups of male Wistar rats were studied: (i) control group (CT group); (ii) gingerol solution control group (GF group); (iii) gentamicin treatment group (GM group), receiving 100 mg/kg of body weight intraperitoneally (i.p.); and (iv to vi) gentamicin groups also receiving GF, at doses of 6.25, 12.5, and 25 mg/kg, respectively (GM+GF groups). Animals from the GM group had a significant decrease in creatinine clearance and higher levels of urinary protein excretion. This was associated with markers of oxidative stress and nitric oxide production. Also, there were increases of the mRNA levels for proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], IL-2, and gamma interferon [IFN-γ]). Histopathological findings of tubular degeneration and inflammatory cell infiltration reinforced GM-induced nephrotoxicity. All these alterations were attenuated by previous oral treatment with GF. Animals from the GM+GF groups showed amelioration in renal function parameters and reduced lipid peroxidation and nitrosative stress, in addition to an increment in the levels of glutathione (GSH) and superoxide dismutase (SOD) activity. Gingerols also promoted significant reductions in mRNA transcription for TNF-α, IL-2, and IFN-γ. These effects were dose dependent. These results demonstrate that GF promotes a nephroprotective effect on GM-mediated nephropathy by oxidative stress, inflammatory processes, and renal dysfunction.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza-CE, Brazil.
authors.forename: Francisco A P
authors.initials: FA
authors.lastname: Rodrigues
authors.forename: Mara M G
authors.initials: MM
authors.lastname: Prata
authors.forename: Iris C M
authors.initials: IC
authors.lastname: Oliveira
authors.forename: Natacha T Q
authors.initials: NT
authors.lastname: Alves
authors.forename: Rosa E M
authors.initials: RE
authors.lastname: Freitas
authors.forename: Helena S A
authors.initials: HS
authors.lastname: Monteiro
authors.forename: Jame's A
authors.initials: JA
authors.lastname: Silva
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Vieira
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Viana
authors.forename: Alexandre B
authors.initials: AB
authors.lastname: Libório
authors.forename: Alexandre
authors.initials: A
authors.lastname: Havt
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D005839:Gentamicins / Q000633:toxicity*; D020939:Zingiber officinale / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002396:Catechols; D005233:Fatty Alcohols; D005839:Gentamicins; D053583:Interleukin-1beta; D007376:Interleukin-2; D017382:Reactive Oxygen Species; C007845:gingerol; D013482:Superoxide Dismutase; D005978:Glutathione