Renal Ornithine Decarboxylase Activity Research Articles

Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats

Iron nitrilotriacetate (Fe-NTA), a chief environmental pollutant, is known for its extensive toxic manifestations on renal system. In the present study, caffeic acid, one of the most frequently occurring phenolic acids in fruits, grains, and dietary supplements was evaluated for its shielding effect against the Fe-NTA-induced oxidative, inflammatory, and pathological damage in kidney. Fe-NTA was administered (9 mg Fe/kg body weight) intraperitoneally to the Wistar male rats on 20th day while caffeic acid was administered orally (20 and 40 mg/kg body weight) before administration of Fe-NTA. The intraperitoneal administration of Fe-NTA-enhanced lipid peroxidation, xanthine oxidase, and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., catalase, glutathione peroxidase, and glutathione reductase. A sharp elevation in the levels of myloperoxidase, blood urea nitrogen (BUN), and serum creatinine has also been observed. Tumor promotion markers viz., ornithine decarboxylase (ODC) and [(3)H] thymidine incorporation into renal DNA were also significantly increased. Treatment of rats orally with caffeic acid (20 and 40 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.001), lipid peroxidation (P < 0.001), γ-glutamyl transpeptidase (P < 0.01), and H(2)O(2) (P < 0.01). There was significant recovery of renal glutathione content (P < 0.001) and antioxidant enzymes (P < 0.001). There was also a reversal in the enhancement of renal ODC activity, DNA synthesis, BUN, and serum creatinine (P < 0.001). All these changes were supported by histological observations. The results indicate that caffeic acid may be beneficial in ameliorating the Fe-NTA-induced oxidative damage and tumor promotion in the kidney of rats.

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.

Antioxidant biofactor, a processed grain food, inhibits iron nitrilotriacetate–induced renal tumorigenesis, hyperproliferative response, and oxidative damage

We have evaluated the effect of dietary antioxidant, antioxidant biofactor (a processed grain food), on iron nitrilotriacetate-induced renal tumorigenesis, hyperproliferative response, and oxidative damage. In tumorigenesis studies, iron nitrilotriacetate alone treatment resulted in a development of 75% renal cell tumor incidence, whereas, in the group of animals fed with antioxidant biofactor diet and treated with iron nitrilotriacetate, only 43% of renal cell tumor incidence was observed. In oxidative damage studies, the decrease in the level of renal glutathione and antioxidant enzymes induced by iron nitrilotriacetate was significantly reversed by antioxidant biofactor diet pretreatment in a dose-dependent manner (18-71% recovery, P < 0.05). Antioxidant biofactor diet pretreatment also resulted in a dose-dependent inhibition (35-49% inhibition, P < 0.05) of iron nitrilotriacetate-induced lipid peroxidation as measured by thiobarbituric acid reactive substances formation in renal tissues. Similarly, in hyperproliferation studies, antioxidant biofactor diet pretreatment showed a strong inhibition of iron nitrilotriacetate-induced renal ornithine decarboxylase activity (18-54% inhibition, P < 0.05). In addition, antioxidant biofactor fed diet pretreatment also protected the kidney tissues against observed histopathological alterations. From this data, it can be concluded that antioxidant biofactor diet can abrogate the toxic and tumor promoting effects of iron nitrilotriacetate and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and tumorigenesis.

Probucol modulates iron nitrilotriacetate (Fe-NTA)-dependent renal carcinogenesis and hyperproliferative response: diminution of oxidative stress

Probucol is a clinically used cholesterol-lowering drug, with pronounced antioxidant properties. We have reported previously, that dietary supplementation of probucol enhances NAD(P)H:quinone reductase (Iqbal M, Okada S (2003) Pharmacol Toxicol 93:259-263) and inhibits Fe-NTA induced lipid peroxidation and DNA damage in vitro (Iqbal M, Sharma SD, Oakada (2004) Redox Rep 9:167-172). Further to this, in the present study, we evaluated the modulatory effect of probucol on iron nitrilotriacetae (Fe-NTA) dependent renal carcinogenesis, hyperproliferative response and oxidative stress. In Fe-NTA alone treated group, a 20% renal cell tumor incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA promoted animals, the percentage tumor incidence was increased to 70% as compared with untreated controls. No tumor incidence was recorded in DEN-initiated, nonpromoted group. Diet supplemented with 1.0% probucol fed prior to, during and after Fe-NTA treatment in DEN-initiated animals afforded >65% protection in renal cell tumor incidence. Probucol fed diet pretreatment also resulted a significant and dose dependent inhibition of Fe-NTA induced renal ornithine decarboxylase (ODC) activity. In oxidative stress studies, Fe-NTA alone treatment enhanced lipid peroxidation, accompanied by a decrease in the level of GSH, activities of antioxidants and phase II metabolizing enzymes in kidney concomitant with histolopathological changes. These changes were significantly and dose-dependently alleviated by probucol fed diet. From this data, it can be concluded that probucol can modulates toxic and tumor promoting effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant induced tissue injury and carcinogenesis, in addition to being a cholesterol lowering and anti-atherogenic drug.

Tumor Promotion and Oxidative Stress in Ferric Nitrilotriacetate–Mediated Renal Carcinogenesis: Protection by Adhatoda vasica

ABSTRACTIn the present study, we report the chemopreventive effects of Adhatoda vasica against ferric nitrilotriacetate (Fe-NTA)–induced renal oxidative stress, hyperproliferative response, and two-stage renal carcinogenesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase (XO), and hydrogen peroxide (H2O2) generation with concomitant reduction in renal glutathione content (GSH), antioxidant enzymes, and phase II metabolizing enzymes. It induces blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity, and [3H] thymidine incorporation into renal DNA. It also enhances DEN (N-diethylnitrosamine)-initiated renal carcinogenesis by increasing the percentage incidences of kidney tumors. Pretreatment of rats orally with A. vasica (50 and 100 mg/kg body weight) resulted in a significant decrease in lipid peroxidation, H2O2 generation, xanthine oxidase (XO), blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (p < 0.001), and incidence of tumors. Renal GSH (p < 0.01), glutathione-metabolizing enzymes (p < 0.001), and antioxidant enzymes were also recovered significantly (p < 0.001). Thus, our results show that A. vasica may meet the criteria demanded from a chemopreventive agent and in a rodent system it can reduce hyperproliferative response toxicity and carcinogenic activity of Fe-NTA.

Effect of Luteolin on Nickel Chloride–Induced Renal Hyperproliferation and Biotransformation Parameters in Wistar Rats

Nickel, a major environmental pollutant, is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of luteolin on nickel chloride (NiCl2)-induced renal oxidative stress, toxicity, and cell proliferation response in male Wistar rats. NiCl2 (250 µmol/kg b.wt./2 mL) enhances reduced renal glutathione content (GSH), glutathione S.-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H2O2 generation, blood urea nitrogen (BUN), and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (GPx) (p < 0.001). NiCl2 administration also dose-dependently induced the renal ornithine decarboxylase (ODC) activity several-fold compared with the activity in saline-treated rats. Similarly, renal DNA synthesis, which is measured as [3H]thymidine incorporation in DNA, is also increased after NiCl2 treatment. Prophylactic treatment of rats with luteolin (10 and 20 µmol/kg b.wt.) daily for 1 week resulted in the diminution of NiCl2-mediated damage as evident from the downregulation of glutathione content, GST, GR, LPO, H2O2 generation, BUN, serum creatinine, DNA synthesis (p < 0.001), and ODC activity (p < 0.01) with concomitant restoration of GPx activity. Thus, the current investigation suggests that luteolin can be used as a chemopreventive agent for cancer prevention as evident from the study where it blocks or suppresses the events associated with chemical carcinogenesis.

Modulatory Effects of Shape Pluchea Lanceolata Against Chemically Induced Oxidative Damage, Hyperproliferation And Two-Stage Renal Carcinogenesis in Wistar Rats

Ferric nitrilotriacetate (Fe-NTA) is a well-established renal carcinogen. Here, we have shown that Pluchea lanceolata (PL) belonging to the family Asteraceae. PL attenuates Fe-NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. It promoted DEN (N-diethyl nitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC) and renal DNA synthesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) also enhances renal lipid peroxidation (LPO), xanthine oxidase (XO) and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content (GSH), antioxidant enzymes, viz., glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), glucose-6-phosphate dehydrogenase and phase-II metabolizing enzymes such as glutathione-S-transferase and quinone reductase (QR). It also enhances blood urea nitrogen (BUN) and serum creatinine. Oral treatment of rats with PL extract (100 and 200 mg/kg body weight) resulted in significant decrease in lipid peroxidation (LPO), xanthine oxidase (XO), H(2)O(2) generation, blood urea nitrogen (BUN), serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), its metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, present study supports PL as a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rat.

Acorus calamus Extracts and Nickel Chloride: Prevention of Oxidative Damage and Hyperproliferation Response in Rat Kidney

Nickel, a major environmental pollutant, is known for its clastogenic, toxic, and carcinogenic potential. In this article, we report the effect of Acorus calamus on nickel chloride (NiCl2)-induced renal oxidative stress, toxicity, and cell proliferation response in male Wistar rats. NiCl2 (250 micromol/kg body weight/mL) enhanced reduced renal glutathione content (GSH), glutathione- S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H2O2 generation, blood urea nitrogen (BUN), and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (GPx) (p < 0.001). NiCl2 administration also dose-dependently induced the renal ornithine decarboxylase (ODC) activity several-fold as compared to salinetreated control rats. Similarly, renal DNA synthesis, which is measured in terms of [3H] thymidine incorporation in DNA, was elevated following NiCl2 treatment. Prophylactic treatment of rats with A. calamus (100 and 200 mg/kg body weight po) daily for 1 wk resulted in the diminution of NiCl2- mediated damage, as evident from the downregulation of glutathione content, GST, GR, LPO, H2O2 generation, BUN, serum creatinine, DNA synthesis (p < 0.001), and ODC activity (p < 0.01) with concomitant restoration of GPx activity. These results clearly demonstrate the role of oxidative stress and its relation to renal disfunctioning and suggest a protective effect of A. calamus on NiCl2-induced nephrotoxicity in a rat experimental model.

Modulatory Effect of Ficus racemosa: Diminution of Potassium Bromate‐Induced Renal Oxidative Injury and Cell Proliferation Response

The aim of the present study was to determine the potential beneficial effects of Ficus racemosa extract. Potassium bromate (KBrO3), a potent nephrotoxic agent that induces renal carcinogenesis and acts as tumour promoter in carcinogen-initiated animals was used as a model to induce renal injury. In this study, we show the chemopreventive effect of Ficus racemosa extract (Moraceae) on KBrO3-mediated renal oxidative stress and cell promotion response in rats. KBrO3 (125 mg/kg body weight, intraperitoneally) enhanced lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content and antioxidant enzymes. KBrO3 treatment also induced tumour promotion markers, viz., ornithine decarboxylase activity and thymidine [3H] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with Ficus racemosa extract (200 mg/kg body weight and 400 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P<0.05), lipid peroxidation (P<0.001), gamma-glutamyl transpeptidase (P<0.001) and H(2O2 (P<0.001). There was significant recovery of renal glutathione content (P<0.01) and antioxidant enzymes (P<0.001). There was also reversal in the enhancement of renal ornithine decarboxylase activity, DNA synthesis, blood urea nitrogen and serum creatinine (P<0.001). Our results suggest that Ficus racemosa extract is a potent chemopreventive agent and suppresses KBrO3-mediated nephrotoxicity in rats.

Inhibition of potassium bromate-induced renal oxidative stress and hyperproliferative response by Nymphaea alba in Wistar rats

KBrO3-mediated renal injury and hyperproliferative response in Wistar rats. In this communication, we report the efficacy of Nymphaea alba on KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, renal antioxidant enzymes and phase-II metabolising enzymes with enhancement in xanthine oxidase, lipid peroxidation, γ-glutamyl transpeptidase and hydrogen peroxide (H2O2). It also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and DNA synthesis. Treatment of rats with Nymphaea alba (100 and 200 mg/kg body weight) one hour before KBrO3 (125 mg/kg body weight, i.p.) resulted in significant decreases in xanthine oxidase lipid peroxidation, γ-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis Renal glutathione content, glutathione metabolizing enzymes and antioxidant enzymes were also recovered to significant levels These results show that Nymphaea alba acts as chemopreventive agent against KBrO3-mediated renal injury and hyperproliferative response.

Chemomodulatory effect of Ficus racemosa extract against chemically induced renal carcinogenesis and oxidative damage response in Wistar rats

Ferric nitrilotriacetate (Fe-NTA) is a well-known renal carcinogen. In this communication, we show the chemopreventive effect of Ficus racemosa extract against Fe-NTA-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, γ-glutamyl transpeptidase and hydrogen peroxide (H 2O 2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione- S-transferase and quinone reductase. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [ 3H] incorporation into renal DNA. It also enhances DEN ( N-diethylnitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors. Treatment of rats orally with F. racemosa extract (200 and 400 mg/kg body weight) resulted in significant decrease in γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H 2O 2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis ( P < 0.001) and incidence of tumors. Renal glutathione content ( P < 0.01), glutathione metabolizing enzymes ( P < 0.001) and antioxidant enzymes were also recovered to significant level ( P < 0.001). Thus, our data suggests that F. racemosa extract is a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rats.

Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa

In an earlier communication we reported that Nigella sativa suppresses potassium bromate-induced renal oxidative damage. In the present study, we report the chemopreventive effect of Nigella sativa against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes and phase II metabolizing enzymes. It also caused increase in blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [H] incorporation into renal DNA. It also enhanced DEN (N-diethylnitrosamine)-initiated renal carcinogenesis by increasing the percentage incidence of tumours. Treatment of rats orally with Nigella sativa (50 and 100 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (P<0.001) and incidence of tumours. Renal glutathione content (P<0.01), glutathione-metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant levels (P<0.001). Thus, our data suggest that Nigella sativa is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats.

Anticarcinogenic effect of Nymphaea alba against oxidative damage, hyperproliferative response and renal carcinogenesis in Wistar rats

The present study investigates the prophylactic effect of Nymphaea alba against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats. Treatment with Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhanced iron-ascorbate-induced renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. It also elevated the levels of blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. It also enhanced DEN-initiated renal carcinogenesis by increasing the percentage incidence of renal tumors. Treatment of rats orally with N. alba (100 and 200 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), glutathione metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, our results show that N. alba is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats.

Influence of dietary arginine on the anabolic effects of androgens

Feeding mice an arginine-deficient diet decreased plasma concentrations of arginine, citrulline and ornithine in the females and arginine in the males, abolishing the sexual dimorphic pattern of these amino acids found in mice fed the standard diet. In addition, the restriction of dietary arginine produced a marked decrease in body and renal weights as well as in the activity of renal ornithine decarboxylase, decreases that were gender dependent since they were observed exclusively in males. The fact that these changes were not associated with the decrease in the circulating levels of testosterone and that the dietary arginine restriction prevented the body weight gain induced by testosterone treatment of female mice fed the standard diet indicates that dietary arginine is required for the anabolic action of androgens. Moreover, under certain conditions that could compromise the renal synthesis of arginine, as in the compensatory renal hypertrophy that follows unilateral nephrectomy, the myotrophic effect of testosterone was transiently impaired. The results also revealed that arginine deficiency produced an opposite effect in the expression of IGF-I and IGF-binding protein 1 in the liver and kidney. Taken together, our results indicate that dietary arginine may be relevant to the anabolic action of testosterone, and suggest that this effect may be mediated by changes in the insulin-like growth factor system.

Suppressive effects of dietary curcumin on the increased activity of renal ornithine decarboxylase in mice treated with a renal carcinogen, ferric nitrilotriacetate

Curcumin, a natural, biologically active compound extracted from rhizomes of Curcuma species, has been shown to act as a biological response modifier in various disorders. We have reported previously that the dietary supplementation of curcumin enhances the activities of antioxidant and phase II metabolizing enzymes in mice (M. Iqbal, S.D. Sharma, Y. Okazaki, M. Fujisawa, S. Okada, Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY mice: possible role in protection against chemical carcinogenesis and toxicity, Pharmacol and Toxicol. 92 (2003) 33_38.) and inhibits ferric nitrilotriacetate (Fe-NTA) induced oxidative injury of lipids and DNA in vitro (M. Iqbal, Y. Okazaki, S. Okada, In vitro curcumin modulates Ferric Nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H(2)O(2))-induced peroxidation of microsomal membrane lipids and DNA damage, Teratogenesis Carcinogenesis and Mutagenesis Supplement 23 (2003) 151-160.). In our present study, Fe-NTA, a known complete renal carcinogen, which generate ROS in vivo, was given intraperitoneally to mice and curcumin was tested for its ability to inhibits oxidative stress and the activity of ornithine decarboxylase (ODC) as well as histopathological changes in the kidney. Substantial changes in glutathione, antioxidant enzymes as well as changes in phase II metabolizing enzymes were observed in the kidney at 12 h after treatment with Fe-NTA (9.0 mg Fe/kg body weight). Effect of oxidative stress induced by Fe-NTA were also demonstrated by the increase in lipid peroxidation as monitored by formation of thiobarbituric acid-reactive substances and 4-hydroxy-2-nonenal (HNE)-modified proteins in kidney. Likewise, the level of protein carbonyl contents, an indicator of protein oxidation was also increased after Fe-NTA administration. However, the changes in these parameters were restored to normal in curcumin-pretreated mice. The ODC activity in the kidney was significantly increased by Fe-NTA, while the increased ODC activity induced by Fe-NTA was normalized in curcumin-pretreated mice. In addition, curcumin pretreatment almost completely prevented kidney biomolecules from oxidative damage and protected the tissue against observed histopathological alterations.

Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones

Ferric nitrilotriacetate (Fe-NTA) is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of soy isoflavones on renal oxidative stress, toxicity and cell proliferation response in Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances γ-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H 2O 2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. Fe-NTA treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [ 3 H ] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in significant decreases in γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H 2O 2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis ( P < 0.001). Renal glutathione content ( P < 0.01), glutathione metabolizing enzymes ( P < 0.001) and antioxidant enzymes were also returned to normal levels ( P < 0.001). Thus, our data suggest that soy isoflavones may be used as an effective chemopreventive agent against Fe-NTA-mediated renal oxidative stress, toxicity and cell proliferation response in Wistar rats.

Abrogation of potassium bromate-induced renal oxidative stress and subsequent cell proliferation response by soy isoflavones in Wistar rats.

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this study, we show the modulatory effect of soy isoflavones on KBrO3-mediated renal oxidative stress and subsequent cell proliferation response in Wistar rats. KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, activities of renal anti-oxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2). KBrO3 treatment also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). There was also significant recovery of renal glutathione content (P < 0.01), anti-oxidant enzymes and phase-II metabolising enzymes (P < 0.001). Thus, our results show that soy isoflavones acts as potent chemopreventive agent against KBrO3-mediated renal oxidative stress, toxicity and subsequent cell proliferation response in Wistar rats.

Amelioration of ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and tumor promotion response by coumarin (1,2-benzopyrone) in Wistar rats

In this study, we report the modulatory effect of coumarin (1,2-benzopyrone) on Ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and tumor promotion response in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, γ-glutamyl transpeptidase and hydrogen peroxide (H 2O 2) generation with reduction in antioxidant enzymes and renal glutathione content. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [ 3H] incorporation into renal DNA. Prophylactic treatment of rats with coumarin (10 and 20 mg/kg body weight) resulted in significant recovery of antioxidant enzymes ( P<0.001) and renal glutathione content ( P<0.01). There was also significant decrease in γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H 2O 2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis ( P<0.001). Thus, our results show that coumarin is a potent chemopreventive agent and suppresses Fe-NTA induced nephrotoxicity in Wistar rats.

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 (KBrO3) mediated nephrotoxicity in Wistar rats. KBrO3 (125 mg/kg body weight, i.p.) enhances γ-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content and antioxidant enzymes. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and [3H]-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 γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 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 KBrO3-mediated renal oxidative stress, toxicity and tumor promotion response in Wistar rats.

Suppressive effects of Active Hexose Correlated Compound on the increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress

Active Hexose Correlated Compound (AHCC), an extract derived from fungi of Basidiomycetes family has been shown to act as a biological response modifier in various disorders. In our present study, ferric nitrilotriacetate (Fe-NTA), which generates hydroxyl radicals in vivo, was given intraperitoneally to rats and AHCC was tested for its ability to suppress oxidative stress and the activity of ornithine decarboxylase (ODC) in the liver and kidney. Substantial increments in glutathione-related enzymes including glutathione reductase, glutathione peroixdase activity as well as oxidized glutahione contents were shown in the liver at 12 h after treatment with Fe-NTA (7.5 mg Fe/kg body weight). Effects of oxidative stress induced by Fe-NTA were also demonstrated by the increase in serum lipid peroxidation, aminotransferases and urinary 8-hydroxy-2′-deoxyguanosine. However, the increases in these parameters were restored to normal in AHCC-pretreated rats. The ODC activity in the liver and kidney was significantly increased by Fe-NTA, while the increased ODC activity induced by Fe-NTA was normalized in AHCC-pretreated rats. These results suggest AHCC acts as a potent antioxidant and protects against disorders induced by oxidative stresses.