Protective effects of pharmacological agents against aminoglycoside-induced nephrotoxicity: A systematic review

ABSTRACT

Introduction: Aminoglycosides have been long used for antibacterial treatment and are still commonly used in clinical practice. Despite their extensive application and positive effects, drug-related toxicity is considered as the main obstacle for aminoglycosides. Aminoglycosides induce nephrotoxicity through the endocytosis and accumulation of the antibiotics in the epithelial cells of proximal tubule. Most importantly, however, a number of pharmacological agents were demonstrated to have protective activities against nephrotoxicity in experimental animals.

Areas covered: In the present systematic review, the authors provide and discuss the mechanisms and epidemiological features of aminoglycoside-induced nephrotoxicity, and focus mainly on recent discoveries and key features of pharmacological interventions. In total, 39 articles were included in this review.

Expert opinion: The majority of studies investigated gentamicin-induced nephrotoxicity in animal models. Antioxidants, chemicals, synthetic drugs, hormones, vitamins, and minerals showed potential values to prevent gentamicin-induced nephrotoxicity. Indicators used to evaluate the effectiveness of nephroprotection included antioxidative indexes, inflammatory responses, and apoptotic markers. Among the nephroprotective agents studied, herbs and natural antioxidant agents showed excellent potential to provide a protective strategy against gentamicin-induced nephrotoxicity.

KEYWORDS:

• Aminoglycosides
• gentamicin
• nephrotoxicity
• pharmacological interventions
• antioxidant agents

Article highlights

• Aminoglycosides have been introduced for more than a half century, and remain a powerful antimicrobial weapon in the arsenal.

• Natural products, chemical agents, synthetic drugs, hormones, vitamins, and minerals exhibit the ability to inhibit aminoglycoside-induced renal damage.

• Natural and chemical agents exert their protective effects against aminoglycoside nephrotoxicity through their antioxidant, anti-inflammatory, and anti-apoptotic activities.

• Herbs and natural products show excellent protective activities against aminoglycoside nephrotoxicity.

• Clinical experience with natural and chemical agents against aminoglycoside nephrotoxicity is much limited and needs more attention and investigation.

This box summarizes key points contained in the article.

Author contributions

All the authors were involved in the conception and drafting of this review. I Karimzadeh, M Abdollahpour-Alitappeh, and M Mahi-Birjand contributed to the conception and design of the study. S Yaghoubi, Z Keshtkaran, and P Peymani researched, collected and analyzed interpreted the data for the first part of the manuscript. N Bagheri, A Pirouzi, K Sineh Sepehr, and M Khatami researched, collected and analyzed data for the second part of the manuscript. S Yaghoubi, A Pirouzi, and K Sineh Sepehr prepared the draft and wrote this review. I Karimzadeh, M Abdollahpour-Alitappeh, and M Mahi-Birjand reviewed and edited the manuscript, and provided detailed feedback. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.