The effects of melatonin on plasma homocysteine and oxidative stress parameters in cisplatin-treated rats
Abstract
The aims of this study were to investigate the effects of cisplatin on nephrotoxicity, plasma homocysteine level and biochemical changes related to oxidative stress and to examine the possible protective role of melatonin administration on these parameters in cisplatin treated rats. In this study, eighteen adult rats were used. The rats were randomly divided into three groups. The first group of rats (control) served as untreated controls andreceived only physiological saline. The second group of rats (CP) was given cisplatin (7 mg/kg) intraperitoneally. Group third of rats received cisplatin (7 mg/kg) and melatonin (10 mg/kg) (CP+Mel) intraperitoneally. Administration of cisplatin to rats induced a marked renal failure, characterized with a significantly increase in plasma creatinine and urea concentrations. While the plasma malondialdehyde level significantly increased, the plasma homocysteine, glutathione levels and glutathione peroxidase, catalase activities significantly decreased in CP group when compared to control group. Although the administration of melatonin to cisplatin treated animals significantly increased the plasma levels of antioxidant enzymes, and decreased markedly the plasma malondialdehyde level, it has no any significant effect on plasma homocysteine level compared to alone cisplatin group. However, melatonin decreased the plasma homocysteine level compared to the control group. This study indicated that melatonin ameliorated the cisplatin-induced oxidative stress, which had the harmful effect on the renal function. However; it was ineffective on plasma homocysteine level in cisplatin-treated rats
References
- Antunes LMG, Darin JDC, Bianchi MLP (2001): Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Res, 43, 145–150.
- Ateşşahin A, Karahan İ, Yılmaz S, Çeribaşı AO, Pirinççi İ (2003): The effect of manganese chloride on gentamicine-induced nephrotoxicity in rats. Pharmacol Res, 48, 637–642.
- Ateşşahin A, Şahna E, Türk G, Çeribaşı AO, Yılmaz S, Yuce A, Bulmuş O (2006): Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res, 41, 21-27.
- Ateşşahin A, Yılmaz S, Karahan İ, Çeribaşı AO, Karaoglu A (2005): Effects of lycopene against cisplatin- induced nephrotoxicity and oxidative stress in rats. Toxicology, 212, 116-123.
- Baydaş G, Yılmaz O, Çelik S, Yaşar A, Gürsu MF (2002): Effects of certain micronutrients and melatonin on plasma lipid, lipid peroxidation, and homocysteine levels in rats. Arch Med Res, 33, 515-519.
- Blom HJ, Kleinveld HA, Boers GH, Demacker PN, Hak-Lemmers HL, Te Poele-Pothoff MT, Trijbels JM (1995): Lipid peroxidation and susceptibility of low- density lipoprotein to in vitro oxidation in hyperhomocysteinaemia. Eur J Clin Invest, 25, 149-154.
- Bouzouf M, Martinez-Cruz F, Molinero P, Guerrero JM, Osuna J (2005): Melatonin prevents hyperho- mocysteinemia and neural lipid peroxidation induced by methionine intake. Curr Neurovasc Res, 2, 175-178.
- Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991): Hyperhomocysteinemia: an independent risk factor for vascular disease. N Eng J Med, 324, 1149-1155.
- Domagala TB, Undas A, Libura M, Szczeklik A (1998): Pathogenesis of vascular disease in hyperhomocysteinaemia. J Cardiovasc Risk, 5, 239-247.
- El-Sokkary GH, Abdel-Rahman GH, Kamel ES (2005): Melatonin protects against lead-induced hepatic and renal toxicity in male rats. Toxicology, 213, 25-33.
- Finkelstein JD, Martin JJ (2000): Homocysteine. Int J Biochem Cell Biol, 32, 385-389.
- Goth L (1991): A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta, 196, 143-152.
- Greggi Antunes LM, Darin JD, Bianchi MP (2000): Protective effects of Vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats. Pharmacol Res, 41, 405–411.
- Hardeland R, Reiter RJ, Poeggeler B, Tan DX (1993): The significance of the metabolism of the neurohormone melatonin: antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev, 17, 347-57.
- Jacobsen DW, Gatautis VJ, Green R, Robinson K, Savon SR, Secic M, Ji J, Otto JM, Taylor LM (1994): Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem, 40, 873-881.
- Kim YK, Jung JS, Lee SH, Kim YW (1997): Effects of antioxidants and Ca2+ in cisplatin-induced cell injury in rabbit renal cortical slices. Toxicol Appl Pharmacol, 146, 261–269.
- Kröning R, Lichtenstein AK, Nagami GT (2000): Sulfur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines. Cancer Chemother Pharmacol, 45, 43-49.
- Lawrence RA, Burk RF (1976): Glutathione peroxidase activity in selenium-deficient rat liver. Bioch Bioph Res Commun, 71, 952-958.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RI (1951): Protein measurement with folin phenol reagent. J Biol Chem, 193, 265-275.
- Martinis BS, Bianchi MLP (2001): Effect of Vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats. Pharmacol Res, 44, 317– 320.
- Mora LO, Antunes LM, Francescato HD, Bianchi MI (2003): The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats. Pharmacol Res, 47, 517–522.
- Nazıroğlu M, Karaoğlu A, Aksoy AO (2004): Selenium and high dose vitamin E administration protects cisplatin- induced oxidative damage to renal, liver and lens tissues in rats. Toxicology, 195, 221–230.
- Placer AZ, Linda LC, Johnson B (1966): Estimation of product of lipid peroxidation (malonyldialdehyde) in biochemical systems. Anal Biochem, 16, 359-64.
- Reiter RJ, Melchiorri D, Sewerynek E, Poeggeler B, Barlow-Walden L, Chuang J, Ortiz GG, Acuna- Castroviejo D (1995): A review of the evidence supporting melatonin's role as an antioxidant. J Pineal Res, 18, 1–11.
- Reiter RJ, Tan DX, Allegra M (2002): Melatonin: reducing molecular pathology and dysfunction due to free radicals and associated reactants. Neuro Endocrinol Lett, 23, 3-8.
- Reiter RJ, Tan DX, Sainz RM, Mayo JC, Lopez-Burillo S (2002): Melatonin: Reducing the toxicity and increasing the efficacy of drugs. J Pharm Pharmacol, 54, 1299-1321.
- Sedlak J, Lindsay RH (1968): Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem, 25, 192-205.
- Tapiero H, Townsend DM, Tew KD (2004): The role of carotenoids in the prevention of human pathologies. Biomed Pharmacother, 58, 100–110.
- Weijl NI, Elsendoorn TJ, Lentjes EG, Hopman GD, Wipkink-Bakker A, Zwinderman AH, Cleton FJ, Osanto S (2004): Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. Eur J Cancer, 40,1713–1723.
- Yılmaz HR, Iraz M, Söğüt S, Özyurt H, Yıldırım Z, Akyol O, Gergerlioğlu S (2004): The effects of erdosteine on the activities of some metabolic enzymes during cisplatin-induced nephrotoxicity in rats. Pharmacol Res, 50, 287–290.
Sisplatin uygulanan ratlarda plazma homosistein ve oksidatif stres parametreleri üzerine melatonininetkileri
Abstract
Bu çalışmada sisplatin uygulan ratlarda oksidatif stres ile ilişkili biyokimyasal değişimler, plazma homosistein düzeyi ve nefrotoksisite üzerine melatoninin etkisi araştırılmıştır. Bu çalışmada 18 erişkin rat kullanıldı. Ratlar rasgele 3 gruba ayrıldı. Birinci grup ratlara (kontrol) sadece serum fizyolojik uygulaması yapıldı. Ikinci grup ratlara (CP) intraperitonal olarak sisplatin (7 mg/kg) uygulandı. Üçüncü grup ratlara sisplatin (7 mg/kg) ve melatonin (10 mg/kg) (CP+Mel) intraperitonal olarak uygulandı. Ratlara sisplatin uygulaması plazma kreatin ve üre konsantrasyonlarının önemli derecede artışıyla karakterize belirgin bir renal bozukluk oluşturdu. Kontrol grubuyla karşılaştırıldığında sisplatin grubunda glutasyon peroksidaz ve katalaz aktivitesinde plazma homosistein ve glutasyon düzeylerinde önemli bir azalma görülürken, plazma malondialdehid düzeyinde önemli derecede bir artış belirlenmiştir. Sadece sisplatin verilen ve sisplatin ve melatoninin birlikte verildiği gruplar karşılaştırıldığında, plazma malondialdehid düzeyi önemli derecede azalırken plazma antioksidan enzim aktivitesi artmış plazma homosistein düzeyinde ise bir değişim saptanmamıştır. Ancak kontrol grubuyla karşılaştırıldığında plazma homosistein düzeyini melatoninin düşürdüğü görülmüştür. Bu çalışmada, melatoninin sisplatinin neden olduğu oksidatif stres ve renal bozukluklar üzerine iyileştirici etkisi bulunduğu, plazma homosistein düzeyleri üzerine ise etkisiz olduğu tespit edilmiştir
References
- Antunes LMG, Darin JDC, Bianchi MLP (2001): Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Res, 43, 145–150.
- Ateşşahin A, Karahan İ, Yılmaz S, Çeribaşı AO, Pirinççi İ (2003): The effect of manganese chloride on gentamicine-induced nephrotoxicity in rats. Pharmacol Res, 48, 637–642.
- Ateşşahin A, Şahna E, Türk G, Çeribaşı AO, Yılmaz S, Yuce A, Bulmuş O (2006): Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res, 41, 21-27.
- Ateşşahin A, Yılmaz S, Karahan İ, Çeribaşı AO, Karaoglu A (2005): Effects of lycopene against cisplatin- induced nephrotoxicity and oxidative stress in rats. Toxicology, 212, 116-123.
- Baydaş G, Yılmaz O, Çelik S, Yaşar A, Gürsu MF (2002): Effects of certain micronutrients and melatonin on plasma lipid, lipid peroxidation, and homocysteine levels in rats. Arch Med Res, 33, 515-519.
- Blom HJ, Kleinveld HA, Boers GH, Demacker PN, Hak-Lemmers HL, Te Poele-Pothoff MT, Trijbels JM (1995): Lipid peroxidation and susceptibility of low- density lipoprotein to in vitro oxidation in hyperhomocysteinaemia. Eur J Clin Invest, 25, 149-154.
- Bouzouf M, Martinez-Cruz F, Molinero P, Guerrero JM, Osuna J (2005): Melatonin prevents hyperho- mocysteinemia and neural lipid peroxidation induced by methionine intake. Curr Neurovasc Res, 2, 175-178.
- Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991): Hyperhomocysteinemia: an independent risk factor for vascular disease. N Eng J Med, 324, 1149-1155.
- Domagala TB, Undas A, Libura M, Szczeklik A (1998): Pathogenesis of vascular disease in hyperhomocysteinaemia. J Cardiovasc Risk, 5, 239-247.
- El-Sokkary GH, Abdel-Rahman GH, Kamel ES (2005): Melatonin protects against lead-induced hepatic and renal toxicity in male rats. Toxicology, 213, 25-33.
- Finkelstein JD, Martin JJ (2000): Homocysteine. Int J Biochem Cell Biol, 32, 385-389.
- Goth L (1991): A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta, 196, 143-152.
- Greggi Antunes LM, Darin JD, Bianchi MP (2000): Protective effects of Vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats. Pharmacol Res, 41, 405–411.
- Hardeland R, Reiter RJ, Poeggeler B, Tan DX (1993): The significance of the metabolism of the neurohormone melatonin: antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev, 17, 347-57.
- Jacobsen DW, Gatautis VJ, Green R, Robinson K, Savon SR, Secic M, Ji J, Otto JM, Taylor LM (1994): Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem, 40, 873-881.
- Kim YK, Jung JS, Lee SH, Kim YW (1997): Effects of antioxidants and Ca2+ in cisplatin-induced cell injury in rabbit renal cortical slices. Toxicol Appl Pharmacol, 146, 261–269.
- Kröning R, Lichtenstein AK, Nagami GT (2000): Sulfur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines. Cancer Chemother Pharmacol, 45, 43-49.
- Lawrence RA, Burk RF (1976): Glutathione peroxidase activity in selenium-deficient rat liver. Bioch Bioph Res Commun, 71, 952-958.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RI (1951): Protein measurement with folin phenol reagent. J Biol Chem, 193, 265-275.
- Martinis BS, Bianchi MLP (2001): Effect of Vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats. Pharmacol Res, 44, 317– 320.
- Mora LO, Antunes LM, Francescato HD, Bianchi MI (2003): The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats. Pharmacol Res, 47, 517–522.
- Nazıroğlu M, Karaoğlu A, Aksoy AO (2004): Selenium and high dose vitamin E administration protects cisplatin- induced oxidative damage to renal, liver and lens tissues in rats. Toxicology, 195, 221–230.
- Placer AZ, Linda LC, Johnson B (1966): Estimation of product of lipid peroxidation (malonyldialdehyde) in biochemical systems. Anal Biochem, 16, 359-64.
- Reiter RJ, Melchiorri D, Sewerynek E, Poeggeler B, Barlow-Walden L, Chuang J, Ortiz GG, Acuna- Castroviejo D (1995): A review of the evidence supporting melatonin's role as an antioxidant. J Pineal Res, 18, 1–11.
- Reiter RJ, Tan DX, Allegra M (2002): Melatonin: reducing molecular pathology and dysfunction due to free radicals and associated reactants. Neuro Endocrinol Lett, 23, 3-8.
- Reiter RJ, Tan DX, Sainz RM, Mayo JC, Lopez-Burillo S (2002): Melatonin: Reducing the toxicity and increasing the efficacy of drugs. J Pharm Pharmacol, 54, 1299-1321.
- Sedlak J, Lindsay RH (1968): Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem, 25, 192-205.
- Tapiero H, Townsend DM, Tew KD (2004): The role of carotenoids in the prevention of human pathologies. Biomed Pharmacother, 58, 100–110.
- Weijl NI, Elsendoorn TJ, Lentjes EG, Hopman GD, Wipkink-Bakker A, Zwinderman AH, Cleton FJ, Osanto S (2004): Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. Eur J Cancer, 40,1713–1723.
- Yılmaz HR, Iraz M, Söğüt S, Özyurt H, Yıldırım Z, Akyol O, Gergerlioğlu S (2004): The effects of erdosteine on the activities of some metabolic enzymes during cisplatin-induced nephrotoxicity in rats. Pharmacol Res, 50, 287–290.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Surgery |
| Journal Section | Research Article |
| Authors | |
| Publication Date | September 1, 2007 |
| Published in Issue | Year 2007 |