the authors and do not necessarily reflect the views of UK Essays.
- 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 withmultidrug-resistantgram-negativebacteria 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.
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 . 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 .
Table I: Drugs which can cause renal failure and their mechanism of toxic effect
|Mechanism of toxic effect||Drugs|
|Direct tubular effect
|NSAIDs, ACE inhibitors, Cyclosporine A, Lithium, Cyclophosphamide, Amphotericin B, Heavy metals, Aminoglycosides, Cisplatin,Radiocontrast media, Immune-globulin, Mannitol|
|Tubular obstruction||Sulphonamides, Acyclovir, Poly ethylene Glycol|
|Acute interstitial nephritis||ß-lactams, Vancomycin, Rrifampicin, Ciprofloxacin, Ranitidine, Cimetidine, Furosemide, Thiazides, Phenytoin|
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 . 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 .
Amikacinisasemisyntheticderivativeoftheaminoglycosideantibiotic,kanamycin.Itisusedinthetreatmentofvarious infection resistancetobacterialaminoglycosideinactivating
andototoxicityislimitingfactorsfor their clinical use and ROS have been found to be involved in these consequences .
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 .
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
|1.||Allium sativum||Amaryllidaceae||Whole||Amikacin (1.2g/kg i.p single dose for 7 days)||Wistar albino rat|||
|2.||Nigella sativa||Ranunculaceae||Seed||Amikacin (1.2g/kg i.p single dose for 7 days)||Wistar albino rat|||
|3.||Punica granatum||Lythraceae||Fruit||Amikacin (80mg/kg daily i.m for 15 days)||Rabbit|||
|4.||Vitis venifera||Vitaceae||Seed||Amikacin (250 mg/kg i.p for 7 days )||Albino Swiss Mice|||
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|||
|2.||Caffeic acid phenethyl ester||Amikacin (i.p. 1.2g/kg at a single dose)||Albino wistar rat|||
|3.||Carnosine||Amikacin (10 mg/kg for 2 weeks s c.)||Albino wistar rat|||
|4.||Erythropoietin||Amikacin(1.2g/kg intraperitoneally at single dose)||Female Sprague Dawley rat|||
|5.||Pentoxifylline||Amikacin (1.2 g/kg i.p. at a single dose)||Albino Wistar rat|||
|6.||Alpha-lipoic acid||Amikacin (1.2 g/kg i.p. at a single dose) for 5 days||Female wistar rat|||
|7.||Montelukast||Amikacin (single dose 1.2 mg/kg i.p.)||Wistar albino female rat|||
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.
- S. J. Chaudhary and A.N Paranjape, “Phytoconstituents of trichosanthes dioica roxa.a harbel therapy for nephrotoxicity”, would journal of pharmacy and pharmaceutical science, vol 3(2),pp.1521-1552, 2014.
- M. Leena, S. V. Kumar, A. Y. Rao, “Drug induced nephrotoxicity and its management”,International Bulletin of Drug Research, vol 2(3), pp.50-65, 2014.
- A.S. Levey, J.P., Bosch, J.B. Lewis, T. Greene, T. Rogers and D. Roth, “A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group”, Ann Intern Med, vol 130(6), pp.461-470, 1999.
- J. W. Graves, “Diagnosis and Management of Chronic Kidney Disease”,Mayo Clin Proc, vol 83(9),pp.1064-1069, 2008.
- Kidney International Supplements vol 2, pp.259–274, 2008.
- D. N. Cruz and M. A. Perazella,“Drug-induced acute tubulointerstitial nephritis: the clinical spectrum”, Hosp Pract,vol 33, pp.151–52,157–8,161–4. 1998.
- N. Gill, V. Joseph, J. Nally and A. F. Richard, “Renal Failure Secondary to Acute Tubular Necrosis”, www.chestjournal.org,vol 128(4), pp. 2847–2863, 2005.
- J. W. Graves, “Diagnosis and Management of Chronic Kidney Disease”, Mayo Clin Proc, vol 83(9), pp.1064-1069, 2008.
- M. Musu, G. Finco, R. Antonucci, E. Polati, D. Sanna, M. Evangelista And D. Ribuffo, “Acute nephrotoxicity of NSAID from the foetus to the adult”,European Review for Medical and Pharmacological Sciences, vol 15 pp.1461-1472,2011.
- E. H. Donald and J. D. Michael, “Angiotensin-Converting Enzyme Inhibitor-Induced Renal Failure: Causes, Consequences, and Diagnostic Uses”, Journal of The American Society of Nephrology, vol 1(6), pp.845-858, 1999.
- B. Ryffel and M. J. Mihatsch, “Cyclosporine Nephrotoxicity”, Toxicol Pathol, vol 14(1), pp.73-82, 2013.
- R. K. Zalups and G. L.Diamond, “Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth”, the Toxicology Bibliographic Information, vol 53(6), pp.336-46, 2014.
- N. Ullah, M. A. Khan, T. Khan and W. Ahmad, “Bioactive traditional plant Cinnamomum zeylanicumsuccessfully combat against nephrotoxic effects of aminoglycosides”, Bangladesh J Pharmacol, vol 8, pp.15-21, 2013.
- M. Nematbakhsh,S. Ebrahimian, M. Tooyserkani, F. E. Jazi, A. Talebi andF. Ashrafi, “Gender Difference in Cisplatin-Induced Nephrotoxicity in a Rat Model: Greater Intensity of Damage in Male Than Female”, Nephrourol Mon, vol 5(3), pp.818–821, 2013.
- W. Mary and N. Peter, “Contrast media-induced nephrotoxicity: identification of patients of patients at risk and algorithms for prevention”, J Vase interv Radiol, vol 12, pp.3-9, 2001.
- G. S. Pazhayattil and C. S. Anushree, “Drug-induced impairment of renal function”, International Journal of Nephrology and Renovascular Disease Dovepress,vol 7, pp.457–468, 2014.
- P. Gunness, K. Aleksa, G. Koren, “The effect of acyclovir on the tubular secretion of creatinine in vitro”, Journal of Translational Medicine, vol 8 pp.139, 2010.
- B. M. Tune, “Nephrotoxicityof beta-lactam antibiotics: mechanisms and strategies for prevention”, Pediatr Nephrol. Vol 11(6), pp.768-772, 1997.
- S. Elyasi,H. Khalini,D. S. Khavidaki and A. Mohammadpour, “Vancomycin inducednephrotoxicity: mechanism, incidence, risk factors and special populations”, Eur J Clin Pharmacol, vol 68(9), pp.1243-1255.
- J. Rossert, “Drug-induced acute interstitial nephritis”, Kidney Int., vol 60(2), pp.804-817, 2001.
- I. J. Simpson, M. R. Marshall and H. Pilmore, “Proton pump inhibitors and acute interstitial nephritis: report and analysis of 15 cases”, Nephrology (Carlton), vol 11(5), pp.381-385, 2006.
- R. D. Adelman, W. L. Spangler, F. Beasom, G. Ishizaki and G. M. Conzelman, “Furosemide enhancement of experimental gentamicin nephrotoxicity: comparison of functional and morphological changes with activities of urinary enzymes”,J Infect Dis, vol 140 (3), pp.342–352, 1979.
- X. Guo and C. Nzerue, “How to prevent, recognize, and treat drug-induced nephrotoxicity”, Cleve Clin J Med, vol 69(4), pp.289-312, 2002.
- E. L. Rosenberg and J. P. Hayslett., “Nephrotoxic Effects of Penicillamine in Cystinuria”,The journal of American medical association, vol 201(9), pp.698-699, 1967.
- M. Zahid, K. Farrukh, A. S. A. Batti and N. I. Ansari, “Morphological changes perduced by aminoglycoside induced nephrotoxicity- an experimental study”, vol 23(6), pp.1-3, 2007.
- J. S. Sandhu, A. Sehgal, O. Gupta, and A. Singh, “Aminoglycoside Nephrotoxicity Revisited Journal, Indian Academy of Clinical Medicine”, vol 8(4), pp.331-334, 2007.
- P. Devbhuti,C. Sengupta and A. Sana, “Amikacin induced lipid profile and peroxidise parameters and their control with ascorbic acid”, International Journal of Current Pharmaceutical Research, vol 2(3), pp. 76-81, 2010.
- B. Prajapati and M. Singha, “Comparative evaluation of the toxicity of Amikacin and Cefepime on rat’s kidney and liver”, International Journal of PharmTech Research, vol 3(4), pp. 2149-2154, 2010.
- M. R. Pinsky, P. Brophy, J. Padilla,E. Paganini, and N. Pannu, “Fluid and volume monitoring” Int J Artif Organs, vol 31(2), pp. 111-126, 2008.
- S Heather. and D. John, “Is parentral nutrition therapy of value in acute renal failure patients?” American Journal of kidney Disease, vol 25, pp. 96-102, 1995.
- A. S. Y. Hounkpatin, R. C. Johnson, P. Guédénon, E. Domingo, C .G. Alimba, M. Boko and P. A. Edorh, Protective Effects of Vitamin C on Haematological Parameters in Intoxicated Wistar Rats with Cadmium, Mercury and Combined Cadmium and Mercury,Int. Res. J. Biological Sci, vol (8), pp. 76-81, 2012.
- M. Jun,V. Venkataraman,M. Razavian,B. Cooper,S. Zoungas,T. Ninomiya,A. C. Ninomiya and V. Perkovic, “Antioxidants for chronic kidney disease”, Cochrane Database Syst Rev, vol 10, 2012.
- D. Wilfred, “Basics in Clinical Nutrition, Nutritional support in renal disease”, The European Journal of Clinical Nutrition and metabolism, vol 5, pp. 54-7. 2010.
- J. Normal, E. William and J. Jhon, “Management of acute renal failure in the pediatric patient. Hemofiltration versus hemodialysis”, American Journal Kidney disease, vol 30, pp. 84-88, 1997.
- I. Abdelaziz and M, Kandeel, “The Protective Effects of Nigella sativa oil and Allium sativum extract on Amikacin-induced Nephrotoxicity”, International journal of pharmacology, vol 7(6), pp. 697-703, 2012.
- I. Hazim, Ahmad, K.A, Saba and Tai, “Protective role of Pomegranate juice in inhibit nephrotoxicity induced by amikacin in Rabbits”, Journal of Advanced Biomedical & Pathobiology Research, vol 3(4), pp. 6-17, 2013.
- H. Kalantari, I. Rashidi, S. Bazgir and A. Dibaei, “protective effect of hydroalcolic extract of red grape seed (vitis venifera) in nephrotoxicity induced by amikacin in mice”, Journal of Natural Pharmaceutical Products, vol 2(2), pp. 87-93, 2007.
- P. Devbhuti,C. Sengupta and A. Saha, “Studies on amikacin induced lipid profil and peroxidation parameter and their control with ascorbic acid”, vol 2(3), 2010.
- H. Parlakpinar, M.K. Ozer, M. Ucar,M. Gaffarogu, N. Vardi, M. Koe and A Acet, “Protective effects of caffeic acid phenethyl ester (CAPE) on amikacin-induced nephrotoxicity in rats”, Cell biochem. funct.,vol 24, pp. 363-367, 2006.
- A. M. K. Mohamed, S. G. Sherin and F. Mohamed and J. Mansoura, “protective effect of carocine on amikacin induced nephrotoxicity in rats”, Forensic Med. Clin. Toxicol, Vol. 18(1), 2010.
- K. Kaynar, R. Aliyazioglu, S. Ersoz, S. Ulusoy, A. Sait, G. Ozkan and M. Cansiz, “Role of erythropoietin in prevention of amikacin-induced nephropathy”, JN, vol (05), pp. 25744-74, 2012.
- M .K. Ozer, H. Asci, M. Oncu, M. yesilot, Savarn, D. Batrammmm and E. Cicek, “Effects of pentoxifylline on amikacin-induced nephrotoxicity in rats”, Ren Fail, vol 31(2), pp. 134–139, 2009.
- H. Asci, M. Saygin, F.M. Cankara, D. Bayram, S. Yesilot, I. A. Candan, and I. Ilhan, “The impact of alpha-lipoic acid on amikacin-induced nephrotoxicity”, Informa Healthcare USA, pp. 1525-6049, 2014.
- E. Kose, A. Beytur, Z. Dogan, Z. Ekincioglu, N. Vardi, K. Cinar, Y. Turkoz, H. Soysal and N. Ekinc, “The effects of montelukast against amikacin-induced acute renal”, European Review for Medical and Pharmacological Sciences damage, vol 16, pp. 503-511, 2012.
- P. Gunness, K. Aleksa and G. Koren, “The effect of acyclovir on the tubular secretion of creatinine in vitro”, Journal of Translational Medicine, vol 8:139, 2010.