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Amikacin Induced Nephrotoxicity: Management and Mechanism

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  • Jasmeen Kaur Savita Kumari Amit Barwal Dr. Anil Sharma

 

Abstract— Nephrotoxicity is one of the most common kidney problem. It occurs when the body is exposed to various agents like drugs like aminoglycoside, antimicrobial agents, NSAIDS etc or toxins such as mercury, lead, arsenic etc. Aminoglycosides are one of the oldest antibiotics used to treat serious infections caused by gram-negative and some gram-positive bacteria. Among aminoglycosides, Amikacin is often used for treating severe, hospital-acquired infections with multidrug-resistantgram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter etc. and also used to treat tuberculosis and non-tubercular mycobacterial infection. Kidney failure is the major side effect of amikacin. The risk of renal failure is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy. The mechanism of renal toxicity of amikacin involves diverse range of pathophysiological mechanisms i.e. oxidative stress, inhibition of specific transporters, inflammation, vascular alterations. All major functional regions of the nephron i.e. glomerulus, proximal tubules, distal tubules and collecting ducts are affected. For the management of amikacin nephrotoxicity, various vitamins and antioxidants are used. In present study, we have mentioned an updated list of herbal plants and compounds that are used as nephroprotective agents in amikacin incuced nephrotoxicity.

Keywords- Nephrotoxicity, Amikacin, Nephroprotective, Oxidative stress, Management, Mechanism.

  1. Introduction

Nephrotoxicity is one of the most common kidney problems and occurs when the body is exposed to a drug or toxin that causes damage to the kidneys. When kidney damage occurs, we are unable to rid our body of excess urine, and wastes [1]. Drug-induced renal failure is common and responsible for a variety of pathological effects on the kidney. Many medications like Aminoglycosides, NSAIDS, Anticancer drugs etc can cause renal dysfunction through various mechanisms including altered intraglomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy , all these may lead to significant morbidity [2].

Table I: Drugs which can cause renal failure and their mechanism of toxic effect

Mechanism of toxic effect

Drugs

Direct tubular effect

Proximal tubule

Distal tubule

NSAIDs[9], ACE inhibitors[10], Cyclosporine A[11], Lithium, Cyclophosphamide, Amphotericin B, Heavy metals[12], Aminoglycosides[13], Cisplatin[14],Radiocontrast media[15], Immune-globulin, Mannitol[16]

Tubular obstruction

Sulphonamides[17], Acyclovir[18], Poly ethylene Glycol

Acute interstitial nephritis

ß-lactams[19], Vancomycin[20], Rrifampicin[21], Ciprofloxacin, Ranitidine, Cimetidine[22], Furosemide[23], Thiazides, Phenytoin[24]

Acute glomerulonephritis

Penicillamine[25]

Aminoglycosides are most commonly used antibiotics worldwide because of certain properties like rapid concentration dependent bactericidal effects, clinical effectiveness, a low rate of true resistance, synergism with other beta lactum antibiotics and low cost of therapy. These are also considered to be very important against many life threatening infections especially against gram negative bacterial infections [26]. Aminoglycosides are polycationic, a property that is responsible for their poor oral absorption, a poor penetration into CSF, and a rapid renal clearance. The polycationic charge also appears to contribute to nephrotoxicity [27].

Amikacinisase misynthetic derivative of the aminoglycoside antibiotic, kanamycin. It is used in the treatment of various infection resistance to bacterial aminoglycoside in activating enzymes. However, aminogly coside induced nephrotoxicity andototoxicity is limiting factors for their clinical use and ROS have been found to be involved in these consequences [28].

The adverse effect of amikacin has been attributed to the development of an array of alterations in proximal tubule epithelium followed by its destruction, thereby causing kidney dysfunction. Amikacin administration is also reported to induce apoptosis, free radical generation and another major adverse effect. Free radicals also play an important role in drug-induced damage to the kidney failure and other organs [29].

Management in Amikacin induced Nephrotoxicity

 

Herbal treatment for Amikacin induced Nephrotoxicity

In the recent years many researchers had studied the effects of different plants used traditionally by indigenous healers and herbalists to support kidney function and treat renal disorders. Normally herbal plants are free from side effects and they are low cost medicines with different protective pathway, which will be beneficial for the people.

Table II: list of plants used in amikacin induced nephrotoxicity

S.No

Botanical name

Family

Plant part

Nephrotoxic

Agent

Animal used

Reference

1.

Allium sativum

Amaryllidaceae

Whole

Amikacin (1.2g/kg i.p single dose for 7 days)

Wistar albino rat

[36]

2.

Nigella sativa

Ranunculaceae

Seed

Amikacin (1.2g/kg i.p single dose for 7 days)

Wistar albino rat

[37]

3.

Punica granatum

Lythraceae

Fruit

Amikacin (80mg/kg daily i.m for 15 days)

Rabbit

[38]

4.

Vitis venifera

Vitaceae

Seed

Amikacin (250 mg/kg i.p for 7 days )

Albino Swiss Mice

[39]

Miscellaneous compounds for amikacin induced nephrotoxicity

There are a various compounds like antioxidents agents etc are used as a protective agent in the amikacin induced nephrotoxicity.

Table III: list of compounds used in amikacin induced nephrotoxicity

S.No

Compound

Nephrotoxic agent

Animal used

Reference

1.

Ascorbic acid

Amikacin(15mg/kg i.m.)

White rabbit

[40]

2.

Caffeic acid phenethyl ester

Amikacin (i.p. 1.2g/kg at a single dose)

Albino wistar rat

[41]

3.

Carnosine

Amikacin (10 mg/kg for 2 weeks s c.)

Albino wistar rat

[42]

4.

Erythropoietin

Amikacin(1.2g/kg intraperitoneally at single dose)

Female Sprague Dawley rat

[43]

5.

Pentoxifylline

Amikacin (1.2 g/kg i.p. at a single dose)

Albino Wistar rat

[44]

6.

Alpha-lipoic acid

Amikacin (1.2 g/kg i.p. at a single dose) for 5 days

Female wistar rat

[45]

7.

Montelukast

Amikacin (single dose 1.2 mg/kg i.p.)

Wistar albino female rat

[46]

Conclusion: Now a day, Amikacin is mostly used for indoor and outdoor patients in the treatment of various infections. Nephrotoxicity is very common side effect produced by amikacin. We concluded that there are various herbal plants and compounds which are used in the treatment of amikacin nephrotoxicity. We suggested that herbal treatment is more benifial as campared to others.

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