Effect of monosodium glutamate on testicular tissue of paclitaxel-treated mice: an experimental study


Background: Paclitaxel (PTX), a chemotherapeutic agent, and monosodium glutamate (MSG) have oxidative effects on testicular tissue.

Objective: In this study, the effects of MSG administration on the exacerbation of testicular tissue alterations related to PTX treatment were evaluated.

Materials and Methods: MSG (30 & 60 mg/kg i.p.) was administrated to six groups (n = 8/each) of adult mice before or after PTX treatment: control, PTX-treated, MSG30 + PTX, MSG60 + PTX, PTX + MSG30, and PTX + MSG60. Following the euthanizing, the body weight measurement, pituitary–testicular axis hormonal analysis and serum lipid peroxidation index assessment was prepared, testicular histomorphometry (tubular diameter and germinal epithelium height), immunohistochemistry of p53 was completed. Microscopic indices of spermatogenesis (tubular differentiation, spermiogenesis and repopulation indices) were studied.

Results: Body weight was not changed significantly. The levels of testosterone (p = 0.0001), follicle stimulating hormone (p = 0.019), and luteinizing hormone (p = 0.08) were decreased while the level of lipid peroxidation index was increased (p = 0.208) in the treated groups. The histomorphometry indices (p < 0.0001 and p = 0.001, respectively), germ cells population (p < 0.05) and microscopic indices of spermatogenesis (p = 0.001, p = 0.005, p < 0.0001, respectively) were significantly reduced in all treated groups. The administration of MSG before PTX treatment induces more changes. The most positive reaction to p53 was observed in MSG30 or 60 + PTX groups compared to other groups.

Conclusion: The administration of MSG could intensify testicular tissue alterations related to PTX chemotherapy.

Key words: Mice, Monosodium glutamate, Morphometry, Paclitaxel, Testicular tissue.

[1] Masocha W. Paclitaxel-induced hyposensitivity to nociceptive chemical stimulation in mice can be prevented by treatment with minocycline. Sci Rep 2014; 4: 6719–6723.

[2] Borovskaya TG, Goldberg VE, Rumpel OA, Pahomova AV, Perova AV, Goldberg ED. The rat spermatogenesis after injection of paclitaxel (Antitumor Agent). Bull Exp Biol Med 2009; 147: 715–718.

[3] Samuels A. The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information. Account Res 1999; 6: 259–310.

[4] Eweka AO, OmIniabohs FAE. Histological studies of the effects of monosodium glutamate on the kidney of adult wistar rats. Internet J Health 2007; 6: 45–67.

[5] Alalwani AD. Monosodium glutamate induced testicular lesions in rats (histological study). Middle East Fertil Society J 2014; 19: 274–280.

[6] Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Oxid Med Cell Longev 2008; 1: 15–24.

[7] Rodrigues AL, da Silva GL, Mateussi AS, Fernandes ES, Miguel OG, Yunes RA, et al. Involvement of monoaminergic system in the anti-depressant like effect of the hydroalcoholic extract of Siphocampylus verticillatus. Life Sci 2002; 70: 1347–1358.

[8] Shetty G, Wilson G, Huhtaniemi I, Shuttlesworth GA, Reissmann T, Meistrich ML. Gonadotropin releasing hormone analogs and testosterone inhibits the recovery of spermatogenesis in irradiated Rats. Endocrinology 2000; 141: 1735–1745.

[9] Kianifard D, Vafaei Saiah G, Rezaee F. Study of the protective effects of quince (cydonia oblonga) leaf extract on fertility alterations and gonadal dysfunction induced by monosodium glutamate in adult male Wistar rats. Rom J Diabetes Nutr Metab Dis 2015; 22: 375–384.

[10] Pizzi WJ, Barnhart JE, Fanslow DJ. Monosodium glutamate administration to the newborn reduces reproductive ability in female and male mice. Science 1977; 196: 452–454.

[11] Park CH, Choi SH, Piao Y, Kim S, Lee YJ, Kim HS, et al. Glutamate and aspartate impair memory retention and damage hypothalamic neurons in adult mice. Toxicol Lett 2000; 115: 117–125.

[12] Miksowiak B, Partyka M. Effects of neonatal treatment with MSG (monosodium glutamate) on hypothalamo-pituitarythyroid axis in adult male rats. Histol Histopathol 1993; 8: 731–734.

[13] Pizzi WJ, Barnhart JE, Unnerstall JR. Reproductive dysfunction in male rats following neonatal administration of monosodium L-glutamate. Neurobehav Toxicol 1979; 1: 1–4.

[14] Onakewhor JUE, Oforofuo IAO, Singh SP. Chronic administration of monosodium glutamate induces oligozoospermia and glycogen accumulation in Wistar rat testes. African Journal Reproductive Health 1998; 2: 193–195.

[15] Gill SS, Mueller RW, Mcguire PF, Pulido OM. Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity. Toxicol Pathol 2000; 28: 277–284.

[16] Takarada T, Hinoi E, Balcar VJ, Taniura H, Yoneda Y. Possible expression of functional glutarnate transporters in the rat testis. J Endocrinol 2004; 181: 233–244.

[17] Maiorino M, Ursini F. Oxidative stress, spermatogenesis and fertility. Biol Chem 2002; 383: 591–597.

[18] Reddy MM, Mahipal SV, Subhashini J, Reddy MC, Roy KR, Reddy PR, et al. Bacterial lipopolysaccharide-induced oxidative stress in the impairment of steroidogenesis and spermatogenesis in rats. Reprod Toxicol 2006; 22: 493–500.

[19] Meshkini A, Yazdanparast R. Involvement of oxidative stress in taxol-induced apoptosis in chronic myelogenous leukemia K562 cells. Exp Toxicol Pathol 2012; 64: 357–365.

[20] Serizawa K, Yogo K, Aizawa K, Tashiro Y, Takahari Y, Sekine K, et al. Paclitaxel-induced endothelial dysfunction in living rats is prevented by nicorandil via reduction of oxidative stress. J Pharmacol Sci 2012; 119: 349–358.

[21] Varbiro G, Veres B, Gallyas FJr, Sumegi B. Direct effect of taxol on free radical formation and mitochondrial permeability transition. Free Radic Biol Med 2011; 31:548–558.

[22] Delkhoshe-Kasmaie F, Malekinejad H, Khoramjouy M, Rezaei-Golmisheh A, Janbaze-Acyabar H. Royal jelly protects from taxol-induced testicular damages via improvement of antioxidant status and up-regulation of E2f1. Syst Biol Reprod Med 2014; 60: 80–88.

[23] Hwang BY, Kim ES, Kim CH, Kwon JY, Kim HK. Gender differences in paclitaxel-induced neuropathic pain behavior and analgesic response in rats. Korean J Anesthesiol 2012; 62: 66–72.

[24] Diniz YS, Faine LA, Galhardi CM, Rodrigues HG, Ebaid GX, Burneiko RC, et al. Monosodium glutamate in standard and high-fiber diets: metabolic syndrome and oxidative stress in rats. Nutrition 2005; 21: 749–755.

[25] Scripture CD, Figg WD, Sparreboom A. Peripheral neuropathy induced by paclitaxel: recent insights and future perspectives. Curr Neuropharmacol 2006; 4: 165–172.

[26] Sakr SA, Badawy GM. Protective effect of curcumin on monosodium glutamate-induced reproductive toxicity in male albino rats. Global J Pharmacol 2013; 7: 416–422.

[27] Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 1969; 164: 719–721.

[28] Garattini S. Glutamic acid, twenty years later. J Nutr 2000; 130 (Suppl.): S901–S909.

[29] Nayanatara AK, Vinodini NA, Damodar G, Ahemed B, Ramaswamy CR, Shabarianth M, et al. Role of ascorbic acid in monosodium glutamate mediated effect on testicular weight, sperm morphology and sperm count, in rat testis. J Chin Clin Med 2008; 3: 1–5.

[30] Kumar N. Taxol-induced polymerization of purified tubulin. Mechanism of action. J Biol Chem 1981; 256: 10435–10441.

[31] Tan G, Heqing L, Jiangbo C, Ming J, Yanhong M, Xianghe L, et al. Apoptosis induced by low-dose paclitaxel is associated with p53 upregulation in nasopharyngeal carcinoma cells. Int J Cancer 2002; 97: 168–172.

[32] Yin Y, Stahl BC, DeWolf WC, Morgentaler A. P53 and Fas are sequential mechanisms of testicular germ cell apoptosis. J Androl 2002; 23: 64–70.

[33] Shukla KK, Mahdi AA, Rajender S. Apoptosis, spermatogenesis and male infertility. Frontiers in Bioscience 2012; 1: 746–754.

[34] Kleinman HK, Klebe RJ, Martin GR. Role of collagenous matrices in the adhesion and growth of cells. J Cell Biol 1981; 88: 473–485.

[35] Li M, He Y, Dubois W, Wu X, Shi J, Huang J. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol Cell 2012; 46: 30–42.

[36] Aitken RJ, Baker MA. Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development. Int J Dev Biol 2013; 57: 265–272.