Protective effect of apocynin against gentamicin-induced nephrotoxicity in rats
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Abstract:
Gentamicin (GNT) is an aminoglycoside antibiotic used for treatment of serious infections, and the nephrotoxic adverse effect is one of the main therapeutic limitations. This study aimed to investigate the possible protective effect of apocynin (APO) on nephrotoxicity induced by GNT in rats. Twenty-four rats were allocated into three groups: control, GNT (100 mg/kg, intraperitoneally (i.p.)), and GNT plus APO (10 mg/kg, i.p.). All rats were killed at the end of the experiment, and then the blood, urine, and kidneys samples were taken. GNT-induced nephrotoxicity was manifested by a significant ( p < 0.05) increase in the weight of kidney, 24-h urine volume, renal somatic index (RSI), protein in urine, serum lactate dehydrogenase (LDH), creatinine (Cr), blood urea nitrogen (BUN), renal Fas ligand (CD95), nitric oxide (NO), and malondialdehyde (MDA). Furthermore, a significant reduction in body weight, creatinine clearance (CCr), serum albumin, renal superoxide dismutase (SOD), and glutathione activities were detected when compared with the control rats. APO ameliorated the nephrotoxic effect and oxidative damage caused by GNT by improving tissue morphology and significantly decreasing 24-h urine volume, RSI, serum Cr, LDH and BUN, protein in urine, and renal content of MDA, CD95, and NO. Additionally, APO caused a significant elevation in renal SOD activity and CCr when compared with the GNT group. These results confirm that APO by its anti-inflammatory, antiapoptotic, and antioxidant effects can ameliorate GNT-induced nephrotoxicity.
Insights
Apocynin (APO) protects against gentamicin (GNT)-induced kidney damage by reducing oxidative stress and inflammation. This study shows APO can be a potential therapeutic agent to mitigate GNT nephrotoxicity.
Area of Science:
- Pharmacology
- Toxicology
- Nephrology
Background:
- Gentamicin (GNT) is a vital antibiotic for serious infections.
- Nephrotoxicity is a significant limitation of GNT therapy.
- Apocynin (APO) is investigated for its potential protective effects.
Purpose of the Study:
- To evaluate the protective effect of apocynin (APO) against gentamicin (GNT)-induced nephrotoxicity in a rat model.
- To elucidate the mechanisms underlying APO's renoprotective properties.
Main Methods:
- Rats were divided into control, GNT-induced nephrotoxicity, and GNT + APO groups.
- Biochemical markers (creatinine, BUN, LDH, albumin), urine analysis, and kidney tissue assessments were performed.
- Levels of oxidative stress markers (MDA, NO) and apoptosis markers (CD95) were measured.
Main Results:
- GNT significantly increased kidney weight, urine volume, serum creatinine, BUN, LDH, and renal oxidative/apoptotic markers.
- GNT significantly decreased body weight, creatinine clearance, and renal antioxidant enzyme activities (SOD, glutathione).
- APO treatment significantly ameliorated GNT-induced kidney injury, improving biochemical parameters, reducing oxidative stress and apoptosis, and enhancing antioxidant capacity.
Conclusions:
- Apocynin exhibits significant anti-inflammatory, antiapoptotic, and antioxidant effects.
- APO effectively ameliorates gentamicin-induced nephrotoxicity in rats.
- APO demonstrates potential as a therapeutic agent to prevent or treat GNT-induced kidney damage.
Related Concept Videos
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:15Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
01:20Estimation of k and VD of Aminoglycosides
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:24Drug Accumulation During Multiple Dosing: Intermittent IV Infusions