Naghma Khan

Nigella sativa (black cumin) ameliorates potassium bromate-induced early events of carcinogenesis: diminution of oxidative stress

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this paper, we report the chemopreventive effect ofNigella sativa (black cumin) on KBrO3-mediated renal oxidative stress, toxicity and tumor promotion response in rats. KBrO3 (125 mg/kg body weight, intraperitoneally) enhances lipid peroxidation, g-glutamyl transpeptidase, hydrogen peroxide and xanthine oxidase with reduction in the activities of renal antioxidant enzymes and renal glutathione content. A marked increase in blood urea nitrogen and serum creatinine has also been observed. KBrO3 treatment also enhances ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into renal DNA. Prophylaxis of rats orally with Nigella sativaextract (50 mg/kg body weight and 100 mg/kg body weight) resulted in a significant decrease in renal microsomal lipid peroxidation (P B-00.001), g-glutamyl transpeptidase (P B-0.001), H2O2 (P B-0.001) and xanthine oxidase (P B-0.05). There was significant recovery of renal glutathione content (P B-0.01) and antioxidant enzymes (P B-0.001). There was also reversal in the enhancement of blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P B-0.001). Data suggest that Nigella sativa is a potent chemopreventive agent and may suppress KBrO3-mediated renal oxidative stress, toxicity and tumour promotion response in 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.

Abstract 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.

CHEMOPREVENTIVE EFFECT OF VITIS VINIFERA EXTRACT ON 12-O-TETRADECANOYL-13-PHORBOL ACETATE-INDUCED CUTANEOUS OXIDATIVE STRESS AND TUMOR PROMOTION IN MURINE SKIN

Vitis vinifera (grapes) is used as a fruit worldwide and known for its pharmacological properties. The present paper assesses the chemopreventive potential of Vitis vinifera against 12-O-tetradecanoyl-13-phorbol acetate (TPA)-mediated tumor promotion in 7,12-dimethyl-benz[a]anthracene (DMBA) initiated mice skin. Skin tumor initiation was achieved by a single topical application of DMBA (40 microg/animal/0.20 ml acetone) to mice. Two weeks after the initiation, promoting agent, TPA (5.0 microg/animal/0.2 ml acetone) was applied two times a week for 20 weeks. Pretreatment of Vitis vinifera 1h prior to each application of TPA resulted in protection against cutaneous tumorigenesis in dose-dependent manner. This inhibition was evident when tumor data was considered as the percentage of mice with tumor and the number of tumors per mouse. We have shown that typical application of Vitis vinifera prior to that of TPA resulted in significant inhibition against TPA-caused induction of epidermal ODC activity (P<0.001) and DNA synthesis. Application of Vitis vinifera at a dose level of 5.0 mg and 10.0 mg kg(-1) body weight in acetone prior to that of TPA treatment resulted in partial significant inhibition of oxidative stress in dose-dependent manner. The concomitant increase in the microsomal lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.001). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes were recovered to the partial significant level. Hence, it can be suggested that Vitis vinifera can be used as a chemopreventive agent against oxidative stress and carcinogenesis.

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.

Modulation of biochemical parameters by Hemidesmus indicus in cumene hydroperoxide-induced murine skin: possible role in protection against free radicals-induced cutaneous oxidatve stress and tumor promotion

Hemidesmus indicus has been shown to possess significant activity against immunotoxicity and other pharmacological and physiological disorders. In this communication, we have shown the modulating effect of H. indicus on cumene hydroperoxide-mediated cutaneous oxidative stress and tumor promotion response in murine skin. Cumene hydroperoxide treatment (30 mg per animal) increased cutaneous microsomal lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes and depletion in the level of glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes was observed. Cumene hydroperoxide treatment also induced the ornithine decarboxylase activity and enhanced the [3H]-thymidine uptake in DNA synthesis in murine skin. Application of ethanolic extract of H. indicus at a dose level of 1.5 and 3.0mg/kg body weight in acetone prior to that of cumene hydroperoxide treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress, epidermal ornithine decarboxylase activity and enhanced DNA synthesis in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation and xanthine oxidase activity were significantly reduced (P<0.01). In addition the depleted level of glutathione, inhibited activities of antioxidants and phase II metabolizing enzymes were recovered to significant level (P<0.05). In summary, our data suggest that H. indicus is an effective chemopreventive agent in skin and capable of ameliorating hydroperoxide-induced cutaneous oxidative stress and tumor promotion.

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, γ-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 γ-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 ≤ 0.001), 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. (Mol Cell Biochem 271: 1–11, 2005)

Inhibition of benzoyl peroxide and ultraviolet-B radiation induced oxidative stress and tumor promotion markers by cycloartenol in murine skin

Abstract The chemopreventive potential of cycloartenol on benzoyl peroxide and UVB radiation-induced cutaneous tumor promotion markers and oxidative stress in murine skin is assessed. Benzoyl peroxide treatment (20 mg/animal/0.2 ml acetone) and UVB radiation (0.420 J/m2/s) caused a decrease in the activities of cutaneous antioxidant enzymes namely, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, phase II metabolizing enzyme such as glutathione-S-transferase and quinone reductase and depletion in the level of cutaneous glutathione. There was also enhancement in cutaneous microsomal lipid peroxidation, xanthine oxidase activity, [14C]-ornithine decarboxylase activity and [3H]-thymidine incorporation into cutaneous DNA. Cycloartenol was topically applied prior to the application of benzoyl peroxide at dose levels of 0.2 mg and 0.4 mg/kg body weight in acetone, which resulted in significant inhibition of epidermal ornithine decarboxylase activity and DNA synthesis (P < 0.001). There was also significant reduction of lipid peroxidation and xanthine oxidase activity (P < 0.001). In addition, the depleted levels of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, were also recovered to a significant level (P < 0.001). The data indicate that cycloartenol is an effective chemopreventive agent in skin carcinogenesis.