Biochemical and Biophysical Research Communications
Protective effects of hydroxytyrosol on gentamicin induced nephrotoxicity in mice
Introduction
Gentamicin (GM) is an aminoglycoside antibiotic which is used in clinical practice to treat severe gram-negative [1]. In spite of undesirable gentamicin side effects, this antibiotic is commonly used. Renal nephrotoxicity is one of the most important adverse effects of gentamicin. These adverse renal effects partly induced by generation of reactive oxygen species (ROS). The abundance of polyunsaturated fatty acids makes the kidney an organ particularly vulnerable to reactive oxygen species (ROS) attack [1], [2].
The Mediterranean diet, recommended by UNESCO as a nutritional prototype of worldwide value, is rich in virgin olive oil. This diet improves oxidative stress, endothelial function, inflammation and risk factors for cardiovascular disease such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile [3], [4]. Virgin olive oil component are bioavailable in humans and have shown antioxidant properties. One of the most important antioxidant compounds of virgin olive oil are dietary phenols. Phenols are compounds with an aromatic ring structure with one or more hydroxyl groups. Bioavailability studies in humans show that the absorption of olive oil phenols is probably larger than 55–66 mol%. Hydroxytyrosol (HT or also known as dihydroxy phenyl ethanol) is one of the most important phenolic compounds in extra virgin olive oil that has anticancer potential, cardioprotective capacity and neuroprotective activity [5], [6], [7].
In addition, some study showed HT has antioxidant activity. HT diminished oxidative stress in hepatoma cells and testes and improved human sperm quality [8], [9]. The antioxidant effect of HT can be attributed to the electron donating ability of hydroxyl groups in the orthoposition and subsequent formation of stable intramolecular hydrogen bonds with the phenoxylic radical [6].
This study was designed to evaluate the protective effects of HT as an antioxidant on gentamicin induced nephrotoxicity in mice. The present research is being carried out to motivation the possible useful effects of the usage of HT as complementary therapy in patients so that recover the side-effects of aminoglycoside such as gentamicin.
Section snippets
Materials and methods
Male mice weighing 25–30 g were housed under controlled environmental conditions (24 ± 2 °C and 12 h light–dark cycle) and allowed free access to standard rat chow and tap water. Animal care was in compliance with the guidelines of the Animal and Human Ethical Committee of Shahroud University of Medical Sciences.
At the first step of experimental design, 27 mice were randomly arranged in three groups: 1- Sham operated, 2-GM group (100 mg/kg, i.p. for 7 days) 3- GM + HT group (2 mg/kg BW; gastric
Results
GM (100 mg/kg for 8 days) led to increase in plasma BUN and creatinine compared with sham group. In addition, fractional excretion of sodium, fractional excretion of potassium, creatinine clearance and urine flow rate were decreased in GM group in contrast to sham group (Table 1).
Moreover, renal tissue SOD and GSH levels decreased and MDA levels increased in GM group compared to sham group (Fig. 1, Fig. 2, Fig. 3). HT administration diminished plasma BUN and creatinine, fractional excretion of
Discussion
Gentamicin-induced nephrotoxicity is mostly characterized by direct tubular injury and can cause renal and other organ failure [1]. The abundance of polyunsaturated fatty acids makes the renal tissue an organ susceptible to ROS. Gentamicin binds to the cell wall phospholipids, which blocks the chain reactions of the phosphatidylinositol pathway leading to the impairment of cell integrity. Reactive oxygen species (ROS) play an important role in gentamicin-mediated nephropathy. It has been proved
Conclusion
In summary, regarding to improvement of renal functional indices and decreasing in oxidative stress in treatment group, it seems that HT has protective effects on renal tissue in mice that have GM injection.
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
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