Dietary supplementation of silymarin protects against chemically induced nephrotoxicity, inflammation and renal tumor promotion response.
Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxicant and a renal carcinogen that induces its effect by causing oxidative stress. The present study was undertaken to explore protective effect of silymarin, a flavonolignan from milk thistle (Silybum marianum), against Fe-NTA mediated renal oxidative stress, inflammation and tumor promotion response along with elucidation of the implicated mechanism(s). Administration of Fe-NTA (10 mg/kg bd wt, i.p.) to Swiss albino mice induced marked oxidative stress in kidney, evident from augmentation in renal metallothionein (MT) expression, depletion of glutathione content and activities of antioxidant and phase II metabolizing enzymes, and enhancement in production of aldehyde products such as 4-hydroxy-2-nonenal. Fe-NTA also significantly activated nuclear factor kappa B (NFkappaB) and upregulated the expression of downstream genes: cyclooxygenase 2 and inducible nitric oxide synthase and enhancing the production of proinflammatory cytokines: tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). However, feeding of 0.5% and 1% silymarin diet conferred a significant protection against Fe-NTA induced oxidative stress and inflammation. It further augmented MT expression, restored the antioxidant armory, ameliorated NFkappaB activation and decreased the expression of proinflammatory mediators. Silymarin also suppressed Fe-NTA induced hyperproliferation in kidney, ameliorating renal ornithine decarboxylase activity and DNA synthesis. From these results, it could be concluded that silymarin markedly protects against chemically induced renal cancer and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.
Kaur
Gurpreet
G
Department of Chemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India. gurpreet6@yahoo.com
Athar
Mohammad
M
Alam
M Sarwar
MS
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004273:DNA, Neoplasm / Q000096:biosynthesis; D019587:Dietary Supplements; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007680:Kidney Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D050217:Metabolic Detoxication, Phase II; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use*; D012838:Silymarin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000447:Aldehydes; D000975:Antioxidants; D016207:Cytokines; D004273:DNA, Neoplasm; D005290:Ferric Compounds; D018836:Inflammation Mediators; D016328:NF-kappa B; D020011:Protective Agents; D012838:Silymarin; D008668:Metallothionein; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D009955:Ornithine Decarboxylase; C027576:4-hydroxy-2-nonenal; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate