He cause of nephrotoxicity at its therapeutic doses and appeared to
He cause of nephrotoxicity at its therapeutic doses and appeared to be a major cause of nonoliguric acute renal failure [1]. Gentamicin is* CI-1011 chemical information Correspondence: [email protected] Contributed equally Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, 44000, Pakistanexcreted through kidneys without degradation or metabolic changes, with 5 to 10 dose is concentrated in proximal tubules vastly exceeding the concurrent serum concentration [2]. Although its exact role in kidney dysfunction is not apparent, it is suggested that the selective accumulation of gentamicin in kidney cortex can induce oxidative stress and cause lipid peroxidation [3]. Additionally, it can mediate the generation of reactive oxygen species (ROS) such as hydroxyl radical, hydrogen peroxide and superoxide anion mostly in mitochondria that can induce renal injuries [3].?2011 Khan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Khan et al. BMC Complementary and Alternative Medicine 2011, 11:113 http://www.biomedcentral.com/1472-6882/11/Page 2 ofGentamicin causes the activation of platelet activation factor ensuing local vasoconstriction and thus reduces the renal blood flow and glomerular filtration rate [4]. Gentamicin induced renal injuries are mostly localized to the proximal tubules because of association of gentamicin with polyanionic inositol phospholipids and megalin, a receptor, for uptake of gentamicin [5,6]. Gentamicin resists the degradation of phospholipids that compromised the lysosomal membrane integrity and eventually the leakage of enzymes. Gentamicin behaves as iron chelator and iron-gentamicin complexes are thought to be involved in free radical formation [7]. Iron, released from the renal cortex mitochondria on account of excessive oxidative stress induced with gentamicin, act as a putative enhancer of gentamicin induced oxidative stress. Oxidative stress is mainly regulated by the cellular enzymatic (catalase, superoxide dismutase, glutathione peroxidase) and nonenzymatic (glutathione, ascorbic acid, a-tocopherol) factors [7]. Recent studies have shown that natural antioxidants obtained from different alternative systems of medicine display a wide range of biological activities. Various alternatives possessing antioxidant properties have been used in order to minimize gentamicin induced oxidative stress in animal models. Many plant extracts have been reported to be effective in ameliorating organ toxicities [8-11]. Prevention of nephrotoxicity induced with gentamicin in rat by grape seed extract might be attributed by the presence of polyphenolic compounds [8]. Green tea extract possesses catechin and other polyphenolic compounds; prevents the gentamicin induced nephrotoxicity in rat [10,11]. Momordica dioica extract also prevented the toxic insult caused by gentamicin in rat [12]. Coenzyme Q10 played a significant role in protecting cells from oxidative stress induced with gentamicin and other agents [9,13]. Another antioxidant that possibly PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/25432023 deactivates ROS is curcumin. This chemical is obtained from Curcuma longa; decreased the oxidative stress induced with gentamicin and is also found beneficial against AIDS [14,15]. Erdosteine, a mucolytic agent also.
