Protective effect of Didymocarpus pedicellata on ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and hyperproliferative response.
Didymocarpus pedicellata R. Br. (Gesneriaceae) is widely used in traditional Indian medicines against renal afflictions. In the present study, we have revealed ethanolic extract of aerial parts of D. pedicellata to possess significant antioxidant activity and protect against ferric nitrilotriacetate (Fe-NTA) mediated renal oxidative stress, nephrotoxicity and tumor promotion response. D. pedicellata extract was found to possess a high content of total polyphenolics, exhibit potent reducing power and significantly scavenge free radicals including several reactive oxygen species (ROS) and reactive nitrogen species (RNS). The extract also significantly and dose-dependently protected against Fe-NTA plus H(2)O(2)-mediated damage to lipids and DNA. Protective efficacy of the extract was also tested in vivo against Fe-NTA mediated nephrotoxicity and tumor promotion response. Administration of Fe-NTA (9 mg/kg body weight, i.p.) to Swiss albino mice depleted renal glutathione content and activities of antioxidant and phase II metabolizing enzymes with concomitant induction of oxidative damage. Fe-NTA also incited hyperproliferation response elevating ornithine decarboxylase activity and [(3)H]-thymidine incorporation into DNA. Elevation in serum creatinine (SCr) and blood urea nitrogen (BUN), and histopathological changes were also evident and suggested Fe-NTA to afflict damage to kidney. Pretreatment of mice with D. pedicellata extract (100-200 mg/kg body weight) for 7 days not only restored antioxidant armory near normal values but also significantly protected against renal oxidative stress and damage restoring normal renal architecture and levels of renal damage markers, viz., BUN and SCr. The results of the present study indicate D. pedicellata to possess potent antioxidant and free radical scavenging activities and preclude oxidative damage and hyperproliferation in renal tissues.
Kaur
Gurpreet
G
Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
Lone
Irshad A
IA
Athar
Mohammad
M
Alam
M Sarwar
MS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000378:metabolism; D005290:Ferric Compounds / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D029001:Herbal Medicine; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects*; D019684:Magnoliopsida / Q000737:chemistry*; D051379:Mice; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D009955:Ornithine Decarboxylase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D020011:Protective Agents; D004247:DNA; D003404:Creatinine; D009955:Ornithine Decarboxylase; D005978:Glutathione; D009571:Nitrilotriacetic Acid; D013936:Thymidine; C020326:ferric nitrilotriacetate