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

Abstract

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.

Keywords

Nigella sativa Linn oxidative stress potassium bromate tumour promotion

References

Sun Y . Free radicals, antioxidant enzymes and carcinogenesis . Free Radic Biol Med 1990; 8: 583–599 .

Ames BN . Dietary carcinogens and anticarcinogens, oxygen radicals and degenerative diseases . Science 1983; 221: 1256–1264 .

Kurokawa Y , Hayashi Y , Maekawa A , Takahashi M , Kokobo T . Induction of renal cell tumors in F-344 rats by oral administration of potassium bromate, a food additive . Gann 1982; 73: 335–338 .

Kurokawa Y , Maekawa A , Takahashi M , Hayashi Y . Toxicity and carcinogenicity of potassium bromate–a new renal carcinogen . Environ Health Perspect 1990; 87: 309–335 .

Umemura T , Sai K , Takagi A , Hasegawa R , Kurokawa Y . A possible role for oxidative stress in potassium bromate carcinogenesis . Carcinogenesis 1995; 116: 587–593 .

Ballmaier D , Epe B . Oxidative DNA damage induced by potassium bromate under cell-free conditions and in mammalian cells . Carcinogenesis 1995; 16: 335–342 .

Khan N , Sharma S , Alam A , Saleem M , Sultana S . Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress and toxicity in Wistar rats . Pharmacol Toxicol 2001; 88: 294–299 .

Katiyar SK , Agarwal R , Wood GS , Mukhtar H . Inhibition of 12-O-tetradecanoyl phorbol acetate caused tumor promotion in 7,12 dimethyl benz (a) anthracene-initiated sencar mouse by a polyphenol fraction . Cancer Res 1992; 52: 6890–6897 .

McLaren J , Boulikas T , Vamvakas S . Induction of poly (ADP ribosylation) in the kidney after in vivo application of renal carcinogen . Toxicology 1994; 88: 101–112 .

10.

Ahmed S , Rahman A , Athar M , Sultana S . Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress . Hum Exp Toxicol 1999; 18: 691–698 .

11.

Ahmed S , Rahman A , Alam A , Saleem M , Athar M , Sultana S . Evaluation of the efficacy of Lawsonia alba in the alleviation of carbon tetrachloride-induced oxidative stress . J Ethnopharmacol 2000; 69: 157–164 .

12.

Alam A , Iqbal M , Saleem M , Ahmed S , Sultana S . Myrica nagi attenuates cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in Swiss albino mice . Pharmacol Toxicol 2000; 86: 209–214 .

13.

Saleem M , Alam A , Ahmed S , Iqbal M , Sultana S . Tephrosia purpurea ameliorates benzoyl peroxide induced cutaneous toxicity in mice: diminution of oxidative stress . Pharm Pharmacol Commun 1999; 5: 1–8 .

14.

Saleem M , Alam A , Sultana S . Attenuation of benzoyl peroxide-mediated cutaneous oxidative stress and hyperproliferative response by the prophylactic treatment of mice with spearmint (Mentha spicata) . Food Chem Toxicol 2000; 38: 939–948 .

15.

Chopra RN , Nayar SL , Chopra IC . Glossary of Indian medicinal plants. New Delhi: National Institute of Science Communication , 1996: 176–177 .

16.

Kapoor LD . CRC handbook of ayurvedic medicinal plants. Boca Raton, FL: CRC Press , 1990: 245-245.

17.

Antonio A , Souza A , Brito RM . Oral anti-inflammatory and anti-ulcerogenic activities of a hydroalcoholic extract and partitioned fraction of Turnera ulmifolia (Turneaceae) . J Ethnopharmacol 1988; 61: 215–228 .

18.

Didry N , Duberwil L , Tratin F , Pinkas M . Antimicrobial activity of aerial parts of Drossera pelitata Smith on oral bacteria . J Ethnopharmacol 1998; 60: 215–228 .

19.

Jollow DJ , Mitchell JR , Zampaglione N , Gillette JR . Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4-bromobezene oxide as the hepatotoxic metabolite . Pharmacology 1974; 11: 151-151 .

20.

Wright JR , Colby HD , Miles PR . Cytosolic factors that affect microsomal lipid peroxidation in lung and liver . Arch Biochem Biophys 1981; 206: 296–304 .

21.

Iqbal M , Sharma SD , Rezazadeh H , Abdulla M , Hasan N , Athar M . Glutathione metabolizing enzymes and oxidative stress in Fe-NTA mediated hepatic injury . Redox Rep 1996; 2: 385–391 .

22.

Kanter MW . Clinical chemistry. USA: The Bobber Merill Company, Inc ., 1975: 80-80.

23.

Hare RS . Endogenous creatinine in serum and urine . Proc Soc Exp Biol Med 1950; 74: 148-148 .

24.

Pick A , Keisari Y . Superoxide anion and H2O2 production by chemically elicited peritoneal macrophages-induction by multiple non phagocytic stimulus . Cell Immunol 1981; 59: 301–308 .

25.

Habig WH , Pabst MJ , Jakoby WB . Glutathione-S-transferases: The first enzymatic step in mercapturic acid formation . J Biol Chem 1974; 249: 7130–7139 .

26.

Mohandas M , Marshall JJ , Duggin GG , Horvath JS , Tiller D . Differential distribution of glutathione and glutathione related enzymes in rabbit kidney . Cancer Res 1984; 44: 5086–5091 .

27.

Carlberg I , Mannervik B . Glutathione level in rat brain . J Biol Chem 1975; 250: 4575–4480 .

28.

Orlowski M , Meister A . -glutamyl cyclotransferase distribution, isozymic forms and specificity . J Biol Chem 1973; 248: 2836–2844 .

29.

Claiborne A . Catalase activity. In Greenwald RA ed. CRC handbook of methods in oxygen radical research. Boca Raton, FL: CRC Press , 1985: 283–284.

30.

Zaheer N , Tiwari KK , Krishnan PS . Exposure and solubilization of hepatic mitochondrial shunt dehydrogenases . Arch Biochem Biophys 1965; 109: 646–648 .

31.

Athar M , Sharma SD , Iqbal M , Sultana S , Pandaya KB , Tripathi IP . Coordination of copper polyamines complex with immidiozoles potentiates its superoxide dismutase mimicking activity and abolishes its interactions with albumin . Biochem Mol Biol Int 1996; 39: 813–821 .

32.

Benson A.M , Hunkalar M.J , Talalay P . Increase of NADPH, quinone reductase activity by dietary antioxidant: Possible role in protection against carcinogenesis and toxicity . Proc Natl Acad Sci USA 1980; 77: 5116–5120 .

33.

O'Brien TG , Simsiman RC , Boutwell RK . Induction of the polyamine biosynthetic enzymes in mouse epidermis by tumor promoting agents . Cancer Res 1975; 35: 1662–1670 .

34.

Smart RC , Huang MT , Conney AH . Sn 1,2-diacylglycerols mimic the effects of TPA in vivo by inducing biochemical changes associated with tumor promotion in mouse epidermis . Carcinogenesis 1986; 7: 1865–1870 .

35.

Giles KW , Myers A . An improved diphenyl method for the estimation of deoxyribonucleic acid . Nature 1965; 206: 93-93 .

36.

Lowry OH , Rosebrough NJ , Farr A , Randall RJ . Protein measurement with the Folin phenol reagent . J Biol Chem 1951; 193: 265–275 .

37.

Morse MA , Stoner GD . Cancer chemoprevention: principles and prospects . Carcinogenesis 1993; 14: 1737–1746 .

38.

Wattenberg LW . Chemoprevention of cancer . Cancer Res 1985; 45: 1–8 .

39.

Cassady JM . Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents . J Nat Prod 1990; 53: 23-41 .

40.

Rastogi RP , Mehrotra BN . Compendium of Indian medicinal plants. New Delhi: CSIR Publication , 1991: 493-493.

41.

Houghton PJ , Zarka R , delas Heras B , Hoult JR . Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation . Planta Med 1995; 61: 33–36 .

42.

Badary O , Nagi MN , Al-Shabanah OA , Al-Sawaf HA , Al-Sohaibani MO , Al-Bekairi AM . Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity . Can J Physiol Pharmacol 1997; 75: 1356–1361 .

43.

Al-Shabanah OA , Badary OA , Nagi MN , Al-Gharably NM , Al-Rikabi AC , Al-Bekairi AM . Thymoquinone protects against doxorubicin–induced cardiotoxicity without compromising its antitumor activity . J Exp Clin Cancer Res 1998; 17: 193–198 .

44.

Al-Gharably NM , Badary OA , Nagi MN , Al-Sawaf HA , Al-Rikabi AC , Al-Bekairi AM . Protective effect of thymoquinone against carbon-tetrachloride hepatotoxicity in mice . Res Commun Pharmacol Toxicol 1997; 2: 41–50 .

45.

El Dakhakhny M , Madi NJ , Lembert N , Ammon HP . Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats J Ethnopharmacol 2002; 81: 161–164 .

46.

Uedo N , Tatsuda M , Iishi H , Baba M , Sakai N , Tano H et al. Inhibition by D-limonene of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats . Cancer Lett 1999; 137: 131–136 .

47.

Pegg AE , Shantz LM , Colemn CS . Ornithine decarboxylase as a target for chemoprevention . J Biol Chem 1995; 22: 132–138 .

48.

Perchellet JP , Perchellet EM . Antioxidants and multistage carcinogenesis in mouse skin . Free Radical Biology and Medicine 1989; 7: 377–408 .

49.

Fuji M , Oikawa K , Saito H , Fukuhara C , Tanaka K . Metabolism of potassium bromate in rats. I: in vitro studies . Chemosphere 1984; 13: 1207–1212 .

50.

Sai K , Tyson CA , Thomas DW , Dabbs JE , Hasegawa R , Kurokawa Y . Oxidative DNA damage induced by potassium bromate in isolated rat renal proximal tubules and renal nuclei . Cancer Lett 1994; 87: 1–7 .

51.

De Flora S , Ramel C . Mechanism of inhibition of mutagenesis and carcinogenesis: classification and overview . Mutat Res 1988; 202: 285–306 .