Role of germanium L-cysteine α-tocopherol complex as stimulator of some antioxidant defense systems in gamma-irradiated rats

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Role of germanium L-cysteine α-tocopherol complex as stimulator of some antioxidant defense systems in gamma-irradiated rats

This study was conducted to evaluate the potency of the newly prepared germanium L-cysteine α-tocopherol complex [germanium dichloro tetrakis (L-cysteinyl-α-tocopherol amide) dichloride] as a protective agent against γ-irradiation-induced free radicals production and liver toxicity. Male Swiss albino rats were injected intraperitoneally with the germanium complex in a concentration of 75 mg kg-1 body mass per dose, for 6 successive doses, last dose administered twenty minutes pre-exposure to a single dose of whole body γ-irradiation of 6.5 Gy. Lipid peroxidation (LPx), nitric oxide (NO), glutathione (GSH) levels, and activity of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in blood and liver. Blood total protein, cholesterol, triglyceride and α-tocopherol content were estimated as well. The results revealed that administration of germanium complex pre-irradiation resulted in significant (p < 0.001) improvement compared to the irradiated group in the level of hepatic and blood LPx. Hepatic GSH revealed a significant increase (p < 0.001), while its level showed no significant variation in blood. Also, the level of NO in blood and liver increased significantly (p < 0.001). On the other hand, pretreatment with the germanium complex normalized the activities of SOD, GPx and CAT in blood and liver when compared to the irradiated group. The study also documents a marked decrease in a blood triglyceride and cholesterol (p < 0.001) and a significant increase (p < 0.001) of α-tocopherol and total protein contents in blood. These biochemical changes were associated with marked improvement of histological status. Therefore, the germanium L-cysteine α-tocopherol complex may be a good candidate for ameliorating the changes induced by irradiation, which indicates the beneficial radio-protective role of this antioxidant agent.

  • S. S. Wallace, Enzymatic processing of radiation-induced free radical damage in DNA, Rad. Res. 150 (Suppl. 5) (1998) S60-S79.

  • L. L. De Zwart, J. H. N. Meerman, J. N. M. Commandeur and N. P. E. Vermeulen, Biomarkers of free radical damage applications in experimental animals and in humans, Free Rad. Biol. Med. 26 (1999) 202-226.

  • Y. Deger, S. Dede, A. Belge, N. Mert, T. Kahraman and M. Alkan, Effects of X-ray radiation on lipid peroxidation and antioxidant systems in rabbits treated with antioxidant compounds, Biol. Trace Elem. Res. 94 (2003) 149-156.

  • P. A. Riley, Free radicals in biology: Oxidative stress and the effects of ionizing radiation, Int. J. Radiat. Biol. 65 (1994) 27-33.

  • M. L. Sagrista, A. E. Garcia, M. Africa De Madariaga and M. Mora, Antioxidant and pro-oxidant effect of the thiolic compounds N-acetyl-L-cysteine and glutathione against free radical-induced lipid peroxidation, Free Radical Res. 36 (2002) 329-340.

  • G. C. Jagetia and T. K. Reddy, Modulation of radiation-induced alteration in the antioxidant status of mice by naringin, Life Sci. 77 (2005) 780-794.

  • A. Badaloo, M. Reid, T. Forrester, W. C. Heird and F. Jahoor, Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition, Am. J. Clin. Nutr. 76 (2002) 646-652.

  • M. K. Yang and Y. G. Kim, Protective role of Ge-132 against paraquat-induced oxidative stress in the livers of senescence-accelerated mice, J. Toxicol. Environ. Health A 58 (1999) 289-297.

  • C. K. Chow, Vitamin E and oxidative stress, Free Rad. Biol. Med. 11 (1991) 215-232.

  • S. Goodman, Therapeutic effect of organic germanium, Med. Hypotheses 26 (1988) 207-215.

  • K. Asai, Mechanism of Action, Miracle Cure Organic Germanium, Japan Publications Inc. Tokyo 1980, pp. 350-375.

  • K. Jayalakshmi, M. Sairam, S. B. Singh, S. K. Sharma, G. Ilavazhagan and P. K. Banerjee, Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture, Brain Res. 1046 (2005) 97-104.

  • M. N. Ghosh, Toxicity Studies, Fundamentals of Experimental Pharmacology, Scientific Book Agency, Calcutta 1984, pp. 153-190.

  • H. J. Conn, M. A. Darrow and V. M. Emmel, Staining Procedure Used by Biological Stain Commission, 2nd ed., Williams & Wilkins Co., Baltimore 1960, pp. 200-245.

  • C. C. Conrad, D. T. Grabowski, C. A. Walter, S. Sabla and A. Richardson, Using MT-/- mice to study metallothionein and oxidative stress, Free Radical Biol. Med. 28 (2000) 447-462.

  • E. Beutler, O. Duron and B. M. Kelly, Improved method of the determination of blood glutathione, J. Lab. Clin. Med. 61 (1963) 882-888.

  • M. Minami and H. Yoshikawa, A simplified assay method of superoxide dismutase, Clin. Chim. Acta 92 (1979) 337-342.

  • L. H. Johansson and L. A. H. Borg, A spectrophotometric method for determination of catalase activity in small tissue sample, Anal. Biochem. 174 (1988) 331-336.

  • D. E. Paglia and W. N. Valentine, Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase, J. Lab. Clin. Med. 70 (1967) 158-169.

  • H. Moshage, B. Kok, J. R. Huizenga and P. L. M. Jansen, Nitrite and nitrate determinations in plasma: A critical evaluation, Clin. Chem. 41 (1995) 892-896.

  • H. Baker and O. Frank, Determination of α-Tocopherol, Clinical Vitaminology, Willy Whitefeather, New York 1968, pp. 172-210.

  • E. A. Bump and J. M. Brown, Role of glutathione in the radiation response of mammalian cells in vitro and in vivo, Pharm. Ther. 47 (1990) 117-136.

  • P. Lestaevel, D. Clarençon, A. Gharib, A. Peinnequin, R. Cespuglio, P. Gourmelon, A. Alonso, J. D. Laval and E. Multon, Nitric oxide voltammetric measurements in the rat brain after gamma irradiation, Rad. Res. 160 (2003) 631-636.

  • R. Radi, J. S. Beckman, K. M. Bush and B. A. Freeman, Peroxynitrite oxidation of sulfhydryls. The cytosolic potential of superoxide and nitric oxide, J. Biol. Chem. 266 (1994) 4244-4250.

  • B. V. Oliinyk, V. A. Baraboi, S. A. Oliinyk and N. O. Horchakova, Effect of splenosid on lipid peroxidation process and glutathione antioxidant system in rats exposed to fractionated radiation, Ukr. Biokhim. Zh. 73 (2001) 73-77.

  • T. Ueda, Y. Toyoshima, T. Moritani, K. Ri, N. Otsuki, T. Kushihashi, H. Yasuhara and T. Hishida, Protective effect of dipyridamole against lethality and LPx in liver and spleen of the ddY mouse after whole-body irradiation, Int. J. Rad. Biol. 69 (1996) 199-204.

  • Y. S. Park, Y. G. Kim, J. C. Chang and D. Y. Kim, Radioprotective effects of red ginseng extracts on antioxidants and lipid peroxidation of the liver in γ-irradiated mice, Korean Biochem. J. 26 (1993) 184-191.

  • E. S. Kempner, Effects of high-energy electrons and gamma rays directly on protein molecules, J. Pharm. Sci. 90 (2001) 1637-1646.

  • R. Wolfa, D. Wolfb and V. Ruoccoc, Vitamin E: The radical protector, J. Eur. Acad. Dermatol. 10 (1998) 103-117.

  • S. Bok, S. Lee, Y. Park, K. Bae, K. Son, T. Jeong and M. Choi, Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and aryl CoA: Cholesterol transferase are lower in rats fed Citrus Peel extract or a mixture of Citrus bioflavonoids, J. Nutr. 129 (1999) 1182-1185.

  • A. Sedlakova, K. Borikova and T. Ahlers, Changes in lipoprotein lipase activity in the adipose tissue and heart on non-lethally X-irradiated rats, Physiol. Bohemoslov. 35 (1986) 400-405.

  • I. Rodemann and S. K. Bamberg, Cellular basis of radiation-induced fibrosis, Radiother. Oncol. 35 (1995) 83-90.

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