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Protective effects of hydroxytyrosol on gentamicin induced nephrotoxicity in mice
Nooshin Ahmadian Chashmi1, Sarvenaz Emadi2, Hossein Khastar3
1Vice-Chancellery of Health, Shahroud University of Medical Sciences, Shahroud, Iran.
Background:
Gentamicin (GM) is an effective and common antibiotic against severe gram-negative infections. However, its nephrotoxic action has limited the extent of its use. The aim of this study was to investigate the protective effects of hydroxytyrosol (HT) on gentamicin induced nephrotoxicity in mice.
Methods:
Male mice (n = 27) were randomly assigned to three groups: (1) Sham, (2) GM (100 mg/kg for 7 days) (3) GM + HT (2 mg/kg BW; gastric gavages, for 7 days). 24-h urine samples were collected on day 8 and then animal were anesthetized. The blood and kidney tissue samples were collected.
Results:
Gentamicin led to increase in plasma BUN and creatinine, fractional excretion of sodium and potassium and decrease in creatinine clearance and urine flow rate. SOD and GSH levels were reduced and MDA was increased in the GM group compared with the sham group. In GM + HT group, plasma BUN and creatinine, fractional excretion of Na, creatinine clearance and urine flow rate were decreased in contrast to GM group. Increase in SOD and GSH activity and decrease in MDA compared to GM group were seen.
Conclusions:
Findings suggest that HT partly protected the kidneys from gentamicin induced nephrotoxicity and it is partly due to antioxidant effect of HT.
Insights
Hydroxytyrosol (HT) offers partial protection against gentamicin-induced nephrotoxicity in mice, primarily through its antioxidant properties. This finding suggests HT may mitigate kidney damage from this common antibiotic.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Gentamicin (GM) is a vital antibiotic for severe gram-negative infections.
- Nephrotoxicity is a significant limitation to gentamicin's clinical use.
- Hydroxytyrosol (HT) is investigated for its potential protective effects.
Purpose of the Study:
- To evaluate the protective role of hydroxytyrosol (HT) against gentamicin-induced nephrotoxicity in a mouse model.
- To elucidate the mechanisms underlying HT's potential renoprotective effects.
Main Methods:
- Male mice were divided into three groups: sham, gentamicin (GM) alone, and GM plus hydroxytyrosol (HT).
- Mice received daily gentamicin (100 mg/kg) for 7 days, with one group also receiving HT (2 mg/kg BW).
- Renal function was assessed via urine collection and analysis of plasma, blood, and kidney tissue.
Main Results:
- Gentamicin administration significantly increased plasma BUN and creatinine, altered electrolyte excretion, and reduced creatinine clearance and urine flow.
- Biomarkers of oxidative stress, including reduced superoxide dismutase (SOD) and glutathione (GSH) levels and increased malondialdehyde (MDA), were observed in the GM group.
- Hydroxytyrosol treatment in the GM+HT group showed improvements in renal function markers and a reduction in oxidative stress compared to the GM-only group.
Conclusions:
- Hydroxytyrosol demonstrates partial protective effects against gentamicin-induced kidney damage in mice.
- The renoprotective action of HT is attributed, in part, to its potent antioxidant capabilities.
- HT may represent a therapeutic strategy to mitigate gentamicin-associated nephrotoxicity.
