Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats

Abstract

The major side effect of gentamicin (GEN) is nephrotoxicity which in turn restricts the clinical use of this drug. In this study, the effect of gallic acid (GA) on gentamicin-induced nephrotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups: control, GEN (100 mg/kg/day), GEN + GA (30 mg/kg/day), GA (30 mg/kg/day). All drug administrations were done intraperitoneally (i.p) for eight consecutive days. Twenty-four hours after the last administration, blood samples were collected to determine serum creatinine (Cr), blood urea nitrogen (BUN). The right kidney was used for histological examination. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were assayed in left renal tissue. Results showed a significant increase in the levels of MDA, NO, Cr, and BUN and decrease of GSH, CAT, GPx, and SOD by GEN administration. Co-administration with GA showed reduction in the levels of MDA, NO, Cr, and BUN and increase in GSH, CAT, GPx, and SOD. Also, the nephroprotective effect of GA was confirmed by the histological examination of the kidneys. The results of our study showed that GA exerts a significant nephroprotective effect against GEN-induced nephrotoxicity.

Outcomes of Gallic Acid on Alternariol Induced Cyto-Morphic and Genotoxic In Vivo Changes in Parotid Gland: 4-HNE Incorporated

“…Marino et al [53] reported GA scavenging efficiency as compared to melatonin, sesamol, protocatechuic acid and capsaicin. In accordance with our results, Reckziegel et al [54] and Ghaznavi, et al [55] confirmed GA-induced elevated levels of SOD and CAT, which reported substantial improvement after GA treatment. The observable amelioration of AOH-induced inflammatory cellular infiltrations in GA group suggests its anti-inflammatory properties.…”

Morphofunctional Changes in Kidneys of Rats With Gentamicin-Induced Acute Kidney Injury and Use of Melatonin

“…Gentamicin-induced nephrotoxicity at the beginning of the development of the pathological process is characterized by the development of oliguric form of renal failure, accompanied by retention azotemia, proteinuria, increased loss of sodium and potassium ions with urine, resulting in hypokalemia (Table 1), which reflects the significant damage and death of proximal tubular cells along with injury of glomeruli, and corresponds to the results of similar experimental studies of other authors [1, 4, 8-12, 17, 18]. According to the obtained results of the morphological examination, histopathological changes, namely the necrosis and degeneration of the proximal tubular epithelial cells in the form of vacuolization and hydropic dystrophy, and glomerular damage ( Figure 2) were revealed for gentamicin nephropathy [3,[8][9][10][11][12]14]. It is known that the most important mechanism of gentamicin nephrotoxicity is the hyperproduction of reactive oxygen species, causing damage to proteins, DNA and peroxidation of lipids, with an alteration of the integrity of cellular membranes and development of morphofunctional disorders [1,17].…”

“…It is known that the most important mechanism of gentamicin nephrotoxicity is the hyperproduction of reactive oxygen species, causing damage to proteins, DNA and peroxidation of lipids, with an alteration of the integrity of cellular membranes and development of morphofunctional disorders [1,17]. This fact conditions numerous research on the effectiveness of prevention of the gentamicin nephropathy, using known and new antioxidants [1,2,4,[8][9][10][11][12]20].…”

“…At that, the maintenance of glomerular filtration may be explained by the direct antioxidant activity of the drug, since reactive oxygen species and nitrogen oxides directly lead to a decrease in GFR [16]. The established renal effects of melatonin in toxic kidney damage correspond to the criteria of nephroprotective action under the conditions of AKI development [2,[8][9][10][11][12].…”

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

“…Interestingly, the adverse effects of GM were significantly improved by 12 days of GA administration (100 mg/kg), showing that the nephroprotective effects of GA against GM nephrotoxicity. More recently, similar studies showed that GA in doses of 30, 200, 400 mg/kg administration for seven or eight consecutive days could improve renal histopathological lesions and kidney dysfunction in rats intoxicated with GM, likely through its antioxidant activities and its ability to maintain the cellular membrane integrity [38]. Also, previous studies indicated that GA could protect the kidney in pathological situations such as lindane induced toxicity [39,40] and RIR [19] through its anti-oxidative properties.…”