Please use this identifier to cite or link to this item: http://krishikosh.egranth.ac.in/handle/1/5810123046
Authors: Udupa, Venkatesha
Advisor: Prakash, Prof. (Dr.) Veeru
Title: Prediction of Drug Induced Nephrotoxicity Using Traditional Markers and Urinary Biomarkers in Sprague Dawley Rats
Publisher: Department of Biochemistry and Biochemical Engineering Jacob School of Biotechnology and Bioengineering Sam Higginbottom University of Agriculture, Technology And Sciences, Allahabad-211007 (U.P.) India
Language: en
Type: Thesis
Pages: 357p.
Agrotags: null
Keywords: Keywords: renal markers, kidney, toxicology, histopathology, gentamicin, cisplatin
Abstract: Consistent, sensitive biomarkers of acute kidney injury in animal models and humans have historically represented a poorly met need for investigators and clinicians. This research work was undertaken to evaluate novel renal markers use in identifying acute kidney injury (AKI) compared to traditional serum biomarkers which show changes when 30-40% of kidney is damaged in experimentally induced nephrotoxicity in male Sprague Dawley rats. Cisplatin and Gentamicin, a known nephrotoxicant is used at 2.5 and 5 mg/kg dose (single dose, intraperitoneal) and 30 and 100 mg/kg/day (subcutaneous) level for 7 consecutive days, respectively. On day 4 and day 8 post treatment, serum and urine samples from these rats were analysed for traditional (serum: blood urea nitrogen and creatinine, urine: protein, albumin and micro albumin (mALB) and novel biomarkers [Clusterin, kidney injury molecule-1 (Kim-1), Lipcalin-2/ Neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C], light and electron (transmission and scanning) microscopic evaluation of kidneys were carried out. Further immunohistochemical localization of Kim-1 was carried out on day 4 and 8 kidney samples as well. Urinary biomarkers were increased several folds as compared to traditional markers at both doses of cisplatin and gentamicin treated rats and were duration and dose dependent. Histological and electron microscopic changes seen on Day 4 and Day 8 were of minimal to mild and moderate to severe in nature at both doses, respectively. Current experimental data suggests urine Clusterin and IP 10 are highly sensitive biomarkers of detecting nephrotoxicity with Cisplatin and Gentamicin in Sprague Dawley rats. Similarly, Kim-1 is also considered highly sensitive renal biomarker for Cisplatin and Gentamicin (only at 100 mg/kg) as the levels increased on day 4 that persisted until day 8 too. Urinary Kim-1 level, immunoreactivity and histological changes further confirms to several published reports and FDA and EMA recommendation that Kim-1 is highly sensitive biomarker for detecting drug induced acute renal injury. The results indicated that the novel urinary biomarkers are sensitive than traditional biomarkers in identifying kidney damage. Kim-l level and immunohistochemical localization demonstrated the correlation of the renal injury. Renal biomarkers is useful in identifying early kidney damage and thus assessing adversity in toxicology studies. In addition, this noninvasive method is useful in diagnosing acute kidney damage in patients when the renal damage is less than 30% which is not detected using traditional biomarkers.
Description: Ph.D. Thesis
Subject: Biochemistry
Theme: Prediction of Drug Induced Nephrotoxicity Using Traditional Markers and Urinary Biomarkers in Sprague Dawley Rats
Research Problem: Prediction of Drug Induced Nephrotoxicity Using Traditional Markers and Urinary Biomarkers in Sprague Dawley Rats
These Type: Ph.D
Issue Date: 2019
Appears in Collections:Thesis



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