Attenuation of potassium bromate-induced nephrotoxicity by coumarin (1,2-benzopyrone) in Wistar rats: chemoprevention against free radical-mediated renal oxidative stress and tumor promotion response.
We report the modulatory effect of coumarin (1,2-benzopyrone) on potassium bromate (KBrO(3)) mediated nephrotoxicity in Wistar rats. KBrO(3) (125 mg/kg body weight, i.p.) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content and antioxidant enzymes. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and [(3)H]-thymidine incorporation into renal DNA. Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01) and antioxidant enzymes were also recovered to significant level (P < 0.001). These results show that coumarin may be used as an effective chemopreventive agent against KBrO(3)-mediated renal oxidative stress, toxicity and tumor promotion response in Wistar rats.
Khan
Naghma
N
Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
Sharma
Sonia
S
Sultana
Sarwat
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D001959:Bromates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D018890:Chemoprevention; D003374:Coumarins / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014969:Xanthine Oxidase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000970:Antineoplastic Agents; D001959:Bromates; D003374:Coumarins; D005609:Free Radicals; C019536:potassium bromate; D004247:DNA; C030123:coumarin; D003404:Creatinine; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D014969:Xanthine Oxidase; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D009955:Ornithine Decarboxylase; D005978:Glutathione