Effect of magnesium sulfate on letrozole-induced oxidative stress in ovarian tissue of adult female Wistar rats
Subject Areas :
Veterinary Clinical Pathology
Zahra Aslahnezhad
1
,
Akram Eidi
2
,
Pejman Mortazavi
3
,
Shahrbanoo Oryan
4
1 - MSc of Animal Physiology, Department of Biology, Faculty of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2 - Professor, Department of Biology, Faculty of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
3 - Associate Professor, Department of Pathobiology, Faculty of Specialized Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran.
4 - Professor, Department of Biology, Kharazmi University, Tehran, Iran.
Received: 2021-11-11
Accepted : 2020-03-16
Published : 2022-05-22
Keywords:
Rat,
antioxidants,
Letrozole,
PCOs,
magnesium sulfate,
Abstract :
Background and Purpose: Magnesium is the fourth most abundant cation and the second most abundant intracellular cation in the human body. Magnesium is involved in many essential physiological functions. It is a co-factor for over 300 enzymatic reactions, many of which involve generation of adenosine triphosphate (ATP), it regulates transmembrane transport of other ions, including calcium and potassium, and stabilizes secondary structures of DNA and RNA. Consequently, magnesium is essential for muscle contraction and relaxation, cardiac rhythm, vascular tone, neurological function, and cell proliferation. Magnesium is required for cell proliferation, cellular energy production, mineral metabolism, bone development, and glucose homeostasis. Nutrition surveys in North America indicate that magnesium consumption is below recommended intakes for a large segment of the population. Furthermore, diseases such as type 2 diabetes and use of certain medications can increase magnesium loss and predispose individuals to magnesium deficiency. The low magnesium intakes in comparison to current recommendations combined with the high prevalence of factors that can increase magnesium requirements raise a concern about widespread Mg deficiency. Biochemical data lend further support. Hypomagnesemia exists in the general population and the incidence is high in certain subpopulations. Since magnesium is required for many enzymatic reactions, Magnesium deficiency can presumably affect numerous physiological processes. Some studies have reported changes in body composition with dietary magnesium restriction. In rats, maternal and postnatal feeding of a magnesium-deficient diet decreased body weight, lean body mass, and fat-free mass and increased percentage body fat in the offspring. In contrast, body weight, fat mass, and lean mass were similar in rats fed a high-fat diet containing normal or low magnesium beginning after weaning. Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with metabolic syndrome. Evidence suggests that oxidative stress and low degrees of chronic inflammation play an important role in the pathogenesis of PCOS. PCOS is the most common endocrine disorder in premenopausal women. PCOS is a common and multifactorial disease that affects approximately 4-18% of all reproductive-aged women in the world. In the clinic, hyperandrogenism and insulin resistance appear to be the major etiological drivers for reproductive and metabolic abnormalities in women with PCOS. While it is believed that anovulation is the main reason for infertility in PCOS patients, accumulating evidence from clinical studies also indicates that the impairment of endometrial function likely causes recurrent pregnancy loss, premature delivery, endometrial hyperplasia, and carcinoma in women with PCOS. Additionally, several lines of evidence suggest that the systemic low-grade inflammation that often coincides with PCOS compromises multiple aspects of fertility. A deficiency in the activity of aromatase was one reasonable intraovarian disturbance in steroidogenesis thought to cause PCOS. Because aromatase catalyzes the rate-limiting step in the biosynthesis of oestrogens from androgens, a decrease in the activity of this enzyme could be expected to result in increased ovarian androgen production and development of PCOS. The purpose of this study, the effect of magnesium sulfate on letrozole-induced oxidative stress was investigated in ovarian tissue of adult female Wistar rats. Materials and Methods: In this study, a total of 36 female rats were randomly divided into 6 groups of 6: The normal control group (intact), the healthy experimental group (magnesium sulfate 100 mg/kg body weight, gavage), ovarian damage control group (letrozole 1 mg/kg body weight, gavage), ovarian damage experimental group (magnesium sulfate 10, 50, and 100 mg/kg body weight together letrozole). The animals were euthanized 24 h after the last dose of the treatment on day 31. Ovaries were immediately obtained after the animals were sacrificed. The ovaries were homogenized and centrifuged. The supernatant was used to assay the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in ovarian tissue were investigated. Data were analyzed using one-way ANOVA and Tukey test. The criterion was significant (p
References:
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Barbagallo, M., Dominguez, L.J., Galioto, A., Ferlisi, A., Cani, C., Malfa, L., et al. (2003). Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X. Molecular Aspects of Medicine, 24(1-3): 39-52.
Casper, R.F. and Mitwally, M.F. (2011). Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clinical Obstetrics and Gynecology, 54(4): 685-695.
Chen, P.C., Guo, C.H., Tseng, C.J., Wang, K.C. and Liu, P.J. (2013). Blood trace minerals concentrations and oxidative stress in patients with obstructive sleep apnea. Journal of Nutrition Health and Aging, 17(8): 639-644.
Choi, Y.H., Miller, J.M., Tucker, K.L., Hu, H. and Park, S.K. (2014). Antioxidant vitamins and magnesium and the risk of hearing loss in the US general population. American Journal of Clinical Nutrition, 99(1): 148-155.
Demougeot, C., Bobillier–chaumonts, C., Mossiat, C. and Berthelot, A. (2004). Effect of diets with different magnesium content in ischemic stroke rats. Neuroscience Letters, 362(1): 17-20.
De Sousa Rocha, V., Della Rosa, F.B., Ruano, R., Zugaib, M. and Colli, C. (2015). Association between magnesium status, oxidative stress and inflammation in preeclampsia: A case–control study. Clinical Nutrition, 34(6): 1166-1171.
Ehrmann, D.A. (2012). Metabolic dysfunction in PCOS: relationship to obstructive sleep apnea. Steroids, 77(4): 290-294.
Eidi, A., Mortazavi, P., Moradi, F., Haeri Rohani, A. and Safi, Sh. (2013). Magnesium attenuates carbon tetrachloride-induced hepatic injury in rats. Magnesium Research, 26(4): 165-175.
Eidi, A., Eshraghi, T., Mortazavi, P., Asghari, A. and Tavangar, M. (2015). Magnesium protects against bile duct ligation-induced liver injury in male Wistar rats. Magnesium Research, 28(1): 32-45.
Fenkci, V., Fenkci, S., Yilmazer, M. and Serteser, M. (2003). Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertility and Sterility, 80(1): 123-127.
Fung, T.T., Manson, J.E., Solomon, C.G., Liu, S., Willett, W.C. and Hu, F.B. (2003). The association between magnesium intake and fasting insulin concentration in healthy middle-aged women. Journal of American College of Nutrition, 22(6): 533-538.
Goodarzi, M.O., Dumesic, D.A., Chazenbalk, G. and Azziz, R. (2011). Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nature Reviews Endocrinology, 7: 219-231.
Goth, L. (1991). A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta, 196(2-3): 143-152.
Huang, Ch.Y., Liou, Y.F., Chung, S., Lin, Y., Jong, G.P., Kuo, C.H., et al. (2010). Role of erk signaling in the neuroprotective efficacy of magnesium sulfate treatment during focal cerebral ischemia in the gerbil cortex. Chinese Journal of Physiology, 53(5): 299-309.
Kafali, H., Iriadam, M., Ozardali, I. and Demir, N. (2004). Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Archives of Medical Research, 35(2): 103-108.
Kharitonova, M., Iezhitsa, I., Zheltova, A., Ozerov, A., Spasov, A. and Skalny, A. (2015). Comparative angioprotective effects of magnesium compounds. Journal of Trace Elements in Medicine and Biology, 29: 227-234.
Manmohan, K., Purnima, M., Pradeepkumar, M. and Rupali, M. (2012). The role of magnesium sulphate in tuberculous meningitis. Journal of Clinical and Diagnostic Research, 6(5): 848-850.
Marklund, S. and Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry, 47(3): 469-474.
Massy, Z.A. and Drueke, T.B. (2012). Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis and survival. Clinical Kidney Journal, 5(1): 52-61.
Mather, H.M., Nisbet, J.A., Burton, G.H., Poston, G.J., Bland, J.M., Bailey, P.A., et al. (1979). Hypomagnesaemia in diabetes. Clinica Chimica Acta, 95(2): 235-242.
Matovic, V., Buha, A., Bulat, Z., Dukic-Cosic, D., Miljkovic, M., Ivanisevic, J., et al. (2012). Route-dependent effects of cadmium/ cadmium and magnesium acute treatment on parameters of oxidative stress in rat liver. Food and Chemical Toxicology, 50(3-4): 552-557.
Morais, J.B., Severo, J.S., Santos, L.R., de Sousa Melo, S.R., de Oliveira Santos, R., de Oliveira, A.R., et al. (2017). Role of magnesium in oxidative stress in individuals with obesity. Biological Trace Element Research, 176(1): 20-26.
Murri, M., Luque-Ramırez, M., Insenser, M., Ojeda, M. and Escobar, H.F. (2013). Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Human Reproduction Update, 19(3): 268-288.
Paglia, D.E. and Valentine, W.N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory Clinical Medicine, 70(1): 158-169.
Pallares, P. and Gonzalez, A. (2009). A new method for induction and synchronization of oestrus and fertile ovulations in mice by using exogenous hormones. Laboratory Animals, 43(3): 295-299.
Rezvanfar, M.A., Ahmadi, A., Shojaei Saadi, H.A., Baeeri, M. and Abdollahi, M. (2012). Molecular mechanisms of a novel selenium based complementary medicine which confers protection against hyperandrogenism-induced polycystic ovary. Theriogenology, 78(3): 620-631.
Rezvanfar, M.A., Shojaei Sadi, H.A., Gooshe, M., Abdolghaffari, A.H., Baeeri, M. and Abdollahi, M. (2014). Ovarian aging-like phenotype in the hyperandrogenism-induced murine model of polycystic ovary. Oxidative Medicine and Cellular Longevity, 2014: 948-951.
Rosanoff, A., Weaver, C.M. and Rude, R.K. (2012). Suboptimal magnesium status in the United States: are the health consequences underestimated. Nutrition Reviews, 70(3): 153-164.
Ruder, E.H., Hartman, T.J., Blumberg, J. and Goldman, M.B. (2008). Oxidative stress and antioxidants: exposure and impact on female fertility. Human Reproduction Update, 14(4): 345-57.
Shi, D. and Vine, D. (2012). Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk. Fertility and Sterility, 98(1): 185-193.
Showell, M.G., Brown, J., Clarke, J. and Hart, R.J. (2013). Antioxidants for female subfertility. Cochrane Database of Systematic Reviews, 8(CD007807): 45-52.
Sun, X., Mei, Y. and Tong, E. (2000). Effect of magnesium on nitric oxide synthase of neurons in cortex during early period of cerebral Ischemia. Journal of Tongji Medical University, 20(1): 135-142.
Sun, J., Jin, C., Wu, H., Zhao, J., Cui, Y., Liu, H., et al. (2013). Effects of electro-acupuncture on ovarian P450arom, P450c17a and mRNA expression induced by letrozole in PCOS rats. PLOS One, 8(11): 782-793.
Thomson, R.L., Buckley, J.D., Lim, S.S., Noakes, M., Clifton, P.M., Norman, R.J., et al. (2010). Lifestyle management improves quality of life and depression in overweight and obese women with polycystic ovary syndrome. Fertility and Sterility, 94(5): 1812-1816.
Vakilian, K., Ranjbar, A., Zarganjfard, A., Mortazavi, M., Vosough-Ghanbari, S., Mashaiee, S., et al. (2009). On the relation of oxidative stress in delivery mode in pregnant women; a toxicological concern. Toxicology Mechanisms and Methods, 19(2): 94-99.
Van Dam, P.S., Van Asbeck, B.S., Erkelens, D.W., Marx, J.J.M., Gipsen, W.H. and Bravenboet, B. (1995). The role of oxidative stress in neuropathy and other diabetic complications. Diabetes Metabolism Research and Reviews, 11(3): 181-192.
Van Voorhis, B.J., Dunn, M.S., Snyder, G.D. and Weiner, C.P. (1994). Nitric oxide: an autocrine regulator of human granulosa-luteal cell steroidogenesis. Endocrinology, 135(5): 1799-1806.
Veltman-Verhulst, S.M., Boivin, J., Eijkemans, M.J. and Fauser, B.J. (2012). Emotional distress is a common risk in women with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies. Human Reproduction Update, 18(6): 638-651.
Wolf, G., Keilhoff, G., Fischer, S. and Hass, P. (1990). Subcutaneously applied magnesium protects reliably against quinolinate-induced N-methyl-D-aspartate (NMDA)-mediated neurodegeneration and convulsions in rats: are there therapeutical implications. Neuroscience Letters, 117(1-2): 207-211.
Zurvarra, F.M., Salvetti, N.R., Mason, J.I., Velazquez, M.M., Alfaro, N.S. and Ortega, H.H. (2009). Disruption in the expression and immunolocalization of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat. Reproduction, Fertility and Development, 21(7): 827-839.
_||_Azliana, J., Jafria, A., Najwa, N., Arfuzir, N., Lambuk, L., Iezhitsa, I., et al. (2017). Protective effect of magnesium acetyltaurate against NMDA-induced retinal damage involves restoration of minerals and trace elements homeostasis. Journal of Trace Elements in Medicine and Biology, 39: 147-154.
Barbagallo, M., Dominguez, L.J., Galioto, A., Ferlisi, A., Cani, C., Malfa, L., et al. (2003). Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X. Molecular Aspects of Medicine, 24(1-3): 39-52.
Casper, R.F. and Mitwally, M.F. (2011). Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clinical Obstetrics and Gynecology, 54(4): 685-695.
Chen, P.C., Guo, C.H., Tseng, C.J., Wang, K.C. and Liu, P.J. (2013). Blood trace minerals concentrations and oxidative stress in patients with obstructive sleep apnea. Journal of Nutrition Health and Aging, 17(8): 639-644.
Choi, Y.H., Miller, J.M., Tucker, K.L., Hu, H. and Park, S.K. (2014). Antioxidant vitamins and magnesium and the risk of hearing loss in the US general population. American Journal of Clinical Nutrition, 99(1): 148-155.
Demougeot, C., Bobillier–chaumonts, C., Mossiat, C. and Berthelot, A. (2004). Effect of diets with different magnesium content in ischemic stroke rats. Neuroscience Letters, 362(1): 17-20.
De Sousa Rocha, V., Della Rosa, F.B., Ruano, R., Zugaib, M. and Colli, C. (2015). Association between magnesium status, oxidative stress and inflammation in preeclampsia: A case–control study. Clinical Nutrition, 34(6): 1166-1171.
Ehrmann, D.A. (2012). Metabolic dysfunction in PCOS: relationship to obstructive sleep apnea. Steroids, 77(4): 290-294.
Eidi, A., Mortazavi, P., Moradi, F., Haeri Rohani, A. and Safi, Sh. (2013). Magnesium attenuates carbon tetrachloride-induced hepatic injury in rats. Magnesium Research, 26(4): 165-175.
Eidi, A., Eshraghi, T., Mortazavi, P., Asghari, A. and Tavangar, M. (2015). Magnesium protects against bile duct ligation-induced liver injury in male Wistar rats. Magnesium Research, 28(1): 32-45.
Fenkci, V., Fenkci, S., Yilmazer, M. and Serteser, M. (2003). Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertility and Sterility, 80(1): 123-127.
Fung, T.T., Manson, J.E., Solomon, C.G., Liu, S., Willett, W.C. and Hu, F.B. (2003). The association between magnesium intake and fasting insulin concentration in healthy middle-aged women. Journal of American College of Nutrition, 22(6): 533-538.
Goodarzi, M.O., Dumesic, D.A., Chazenbalk, G. and Azziz, R. (2011). Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nature Reviews Endocrinology, 7: 219-231.
Goth, L. (1991). A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta, 196(2-3): 143-152.
Huang, Ch.Y., Liou, Y.F., Chung, S., Lin, Y., Jong, G.P., Kuo, C.H., et al. (2010). Role of erk signaling in the neuroprotective efficacy of magnesium sulfate treatment during focal cerebral ischemia in the gerbil cortex. Chinese Journal of Physiology, 53(5): 299-309.
Kafali, H., Iriadam, M., Ozardali, I. and Demir, N. (2004). Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Archives of Medical Research, 35(2): 103-108.
Kharitonova, M., Iezhitsa, I., Zheltova, A., Ozerov, A., Spasov, A. and Skalny, A. (2015). Comparative angioprotective effects of magnesium compounds. Journal of Trace Elements in Medicine and Biology, 29: 227-234.
Manmohan, K., Purnima, M., Pradeepkumar, M. and Rupali, M. (2012). The role of magnesium sulphate in tuberculous meningitis. Journal of Clinical and Diagnostic Research, 6(5): 848-850.
Marklund, S. and Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry, 47(3): 469-474.
Massy, Z.A. and Drueke, T.B. (2012). Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis and survival. Clinical Kidney Journal, 5(1): 52-61.
Mather, H.M., Nisbet, J.A., Burton, G.H., Poston, G.J., Bland, J.M., Bailey, P.A., et al. (1979). Hypomagnesaemia in diabetes. Clinica Chimica Acta, 95(2): 235-242.
Matovic, V., Buha, A., Bulat, Z., Dukic-Cosic, D., Miljkovic, M., Ivanisevic, J., et al. (2012). Route-dependent effects of cadmium/ cadmium and magnesium acute treatment on parameters of oxidative stress in rat liver. Food and Chemical Toxicology, 50(3-4): 552-557.
Morais, J.B., Severo, J.S., Santos, L.R., de Sousa Melo, S.R., de Oliveira Santos, R., de Oliveira, A.R., et al. (2017). Role of magnesium in oxidative stress in individuals with obesity. Biological Trace Element Research, 176(1): 20-26.
Murri, M., Luque-Ramırez, M., Insenser, M., Ojeda, M. and Escobar, H.F. (2013). Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Human Reproduction Update, 19(3): 268-288.
Paglia, D.E. and Valentine, W.N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory Clinical Medicine, 70(1): 158-169.
Pallares, P. and Gonzalez, A. (2009). A new method for induction and synchronization of oestrus and fertile ovulations in mice by using exogenous hormones. Laboratory Animals, 43(3): 295-299.
Rezvanfar, M.A., Ahmadi, A., Shojaei Saadi, H.A., Baeeri, M. and Abdollahi, M. (2012). Molecular mechanisms of a novel selenium based complementary medicine which confers protection against hyperandrogenism-induced polycystic ovary. Theriogenology, 78(3): 620-631.
Rezvanfar, M.A., Shojaei Sadi, H.A., Gooshe, M., Abdolghaffari, A.H., Baeeri, M. and Abdollahi, M. (2014). Ovarian aging-like phenotype in the hyperandrogenism-induced murine model of polycystic ovary. Oxidative Medicine and Cellular Longevity, 2014: 948-951.
Rosanoff, A., Weaver, C.M. and Rude, R.K. (2012). Suboptimal magnesium status in the United States: are the health consequences underestimated. Nutrition Reviews, 70(3): 153-164.
Ruder, E.H., Hartman, T.J., Blumberg, J. and Goldman, M.B. (2008). Oxidative stress and antioxidants: exposure and impact on female fertility. Human Reproduction Update, 14(4): 345-57.
Shi, D. and Vine, D. (2012). Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk. Fertility and Sterility, 98(1): 185-193.
Showell, M.G., Brown, J., Clarke, J. and Hart, R.J. (2013). Antioxidants for female subfertility. Cochrane Database of Systematic Reviews, 8(CD007807): 45-52.
Sun, X., Mei, Y. and Tong, E. (2000). Effect of magnesium on nitric oxide synthase of neurons in cortex during early period of cerebral Ischemia. Journal of Tongji Medical University, 20(1): 135-142.
Sun, J., Jin, C., Wu, H., Zhao, J., Cui, Y., Liu, H., et al. (2013). Effects of electro-acupuncture on ovarian P450arom, P450c17a and mRNA expression induced by letrozole in PCOS rats. PLOS One, 8(11): 782-793.
Thomson, R.L., Buckley, J.D., Lim, S.S., Noakes, M., Clifton, P.M., Norman, R.J., et al. (2010). Lifestyle management improves quality of life and depression in overweight and obese women with polycystic ovary syndrome. Fertility and Sterility, 94(5): 1812-1816.
Vakilian, K., Ranjbar, A., Zarganjfard, A., Mortazavi, M., Vosough-Ghanbari, S., Mashaiee, S., et al. (2009). On the relation of oxidative stress in delivery mode in pregnant women; a toxicological concern. Toxicology Mechanisms and Methods, 19(2): 94-99.
Van Dam, P.S., Van Asbeck, B.S., Erkelens, D.W., Marx, J.J.M., Gipsen, W.H. and Bravenboet, B. (1995). The role of oxidative stress in neuropathy and other diabetic complications. Diabetes Metabolism Research and Reviews, 11(3): 181-192.
Van Voorhis, B.J., Dunn, M.S., Snyder, G.D. and Weiner, C.P. (1994). Nitric oxide: an autocrine regulator of human granulosa-luteal cell steroidogenesis. Endocrinology, 135(5): 1799-1806.
Veltman-Verhulst, S.M., Boivin, J., Eijkemans, M.J. and Fauser, B.J. (2012). Emotional distress is a common risk in women with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies. Human Reproduction Update, 18(6): 638-651.
Wolf, G., Keilhoff, G., Fischer, S. and Hass, P. (1990). Subcutaneously applied magnesium protects reliably against quinolinate-induced N-methyl-D-aspartate (NMDA)-mediated neurodegeneration and convulsions in rats: are there therapeutical implications. Neuroscience Letters, 117(1-2): 207-211.
Zurvarra, F.M., Salvetti, N.R., Mason, J.I., Velazquez, M.M., Alfaro, N.S. and Ortega, H.H. (2009). Disruption in the expression and immunolocalization of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat. Reproduction, Fertility and Development, 21(7): 827-839.