title: Evaluation of abrin induced nephrotoxicity by using novel renal injury markers.
abstract: Abrin is a potent plant toxin analogous to ricin that is derived from the seeds of Abrus precatorius plant. It belongs to the family of type II ribosome-inactivating proteins and causes cell death by irreversibly inactivating ribosomes through site-specific depurination. In this study we examined the in vivo nephrotoxicity potential of abrin toxin in terms of oxidative stress, inflammation, histopathological changes and biomarkers of kidney injury. Animals were exposed to 0.5 and 1.0 LD50 dose of abrin by intraperitoneal route and observed for 1, 3, and 7 day post-toxin exposure. Depletion of reduced glutathione and increased lipid peroxidation levels were observed in abrin treated mice. In addition, abrin also induced inflammation in the kidneys as observed through expression of MMP-9 and MMP-9/NGAL complex in abrin treated groups by using zymography method. Nephrotoxicity was also evaluated by western blot analysis of kidney injury biomarkers including Clusterin, Cystatin C and NGAL, and their results indicate severity of kidney injury in abrin treated groups. Kidney histology confirmed inflammatory changes due to abrin. The data generated in the present study clearly prove the nephrotoxicity potential of abrin.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Sant
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: P V Lakshmana
authors.initials: PV
authors.lastname: Rao
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: D P
authors.initials: DP
authors.lastname: Nagar
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: S C
authors.initials: SC
authors.lastname: Pant
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India. Electronic address: bhaskar@drde.drdo.in.
authors.forename: A S B
authors.initials: AS
authors.lastname: Bhasker
mesh_terms: D000036:Abrin / Q000633:toxicity*; D029912:Abrus / Q000737:chemistry; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D005978:Glutathione / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D000071068:Lipocalin-2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D012639:Seeds / Q000737:chemistry; D014118:Toxins, Biological / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000071068:Lipocalin-2; D014118:Toxins, Biological; D014409:Tumor Necrosis Factor-alpha; C071332:Lcn2 protein, mouse; D000036:Abrin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D005978:Glutathione
keywords: Abrin; Nephrotoxicity; Oxidative stress; Plant toxin