Pistachio supplementation attenuates motor and cognition impairments induced by cisplatin or vincristine in rats


Department of Neuroscience, Neuroscience Research Center, Neuropharamcology Institute, Kerman University of Medical Sciences, Kerman, Iran


Background: A large number of natural products and dietary components have been evaluated as potential chemoprotective agents. In the present investigation we report the effects of treatment with the dietary antioxidant, pistachio, on cisplatin- or vincristine-induced neurotoxicity in male Wistar rats.
Materials and Methods: Dietary pistachio (10%) was assessed for its neuroprotective effects through the alteration in performance of hippocampus- and cerebellum-related behaviors following chronic cisplatin (5 mg/kg) or vincristine (0.2 mg/kg) treatment in male rats. We also evaluated the effects of cisplatin, vincristine, and pistachio administration on nociception. Six behavioral tasks were used: open field, rotarod, grasping, Morris water maze (MWM), hot plate, and motor nerve conductive velocity (MNCV).
Results: We showed that the exposure of adolescent rats to cisplatin or vincristine resulted in a significant decrease in explorative behaviors and memory retention. Pistachio consumption somewhat improved memory and motor abilities in cisplatin- or vincristine-treated rats, while pistachio alone did not show any significant changes in these abilities compared to saline. Cisplatin and vincristine increased the latency of response to nociception, and pistachio did not reverse this effect.
Conclusion: We conclude that pistachio in the diet following anticancer drugs such as cisplatin and vincristine might have a protective effect against anticancer drug-induced disruptions in motor and cognitive function. However, further studies are needed to elucidate the exact mechanisms of this protective effect of pistachio.


Kamisli S, Ciftci O, Kaya K, Cetin A, Kamisli O, Ozcan C. Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced oxidative, histological and electromyographical side effects in rats. Toxicol Ind Health 2013. [Epub ahead of print].  Back to cited text no. 1
Ali BH, Al-Salam S, Al Husseini IS, Al-Lawati I, Waly M, Yasin J, et al. Abrogation of cisplatin-induced nephrotoxicity by emodin in rats. Fundam Clin Pharmacol 2013;27:192-200.  Back to cited text no. 2
Paksoy M, Ayduran E, Sanlý A, Eken M, Aydýn S, Oktay ZA. The protective effects of intratympanic dexamethasone and vitamin E on cisplatin-induced ototoxicity are demonstrated in rats. Med Oncol 2011;28:615-21.  Back to cited text no. 3
Screnci D, McKeage MJ. Platinum neurotoxicity: Clinical profiles, experimental models and neuroprotective approaches. J Inorg Biochem 1999;77:105-10.  Back to cited text no. 4
Sweeney CJ, Zhu J, Sandler AB, Schiller J, Belani CP, Langer C, et al. Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594: A Phase II trial in patients with metastatic nonsmall cell lung carcinoma. Cancer 2001;92:2639-47.  Back to cited text no. 5
Ta LE, Espeset L, Podratz J, Windebank AJ. Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding. Neurotoxicology 2006;27:992-1002.  Back to cited text no. 6
Li G, Liu W, Frenz D. Cisplatin ototoxicity to the rat inner ear: A role for HMG1 and iNOS. Neurotoxicology 2006;27:22-30.  Back to cited text no. 7
Gu L, Kelm MA, Hammerstone JF, Beecher G, Holden J, Haytowitz D, et al. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J Nutr 2004;134:613-7.  Back to cited text no. 8
Kay CD, Gebauer SK, West SG, Kris-Etherton PM. Pistachios increase serum antioxidants and lower serum oxidized-LDL in hypercholesterolemic adults. J Nutr 2010;140:1093-8.  Back to cited text no. 9
Goli AH, Barzegar M, Sahari MA. Antioxidant activity and total phenolic compounds of pistachio (Pistachia vera) hull extracts. Food Chemi 2005;92:521-5.  Back to cited text no. 10
Tomaino A, Martorana M, Arcoraci T, Monteleone D, Giovinazzo C, Saija A. Antioxidant activity and phenolic profile of pistachio (Pistacia vera L., variety Bronte) seeds and skins. Biochimie 2010;92:1115-22.  Back to cited text no. 11
Dreher ML. Pistachio nuts: Composition and potential health benefits. Nutr Rev 2012;70:234-40.  Back to cited text no. 12
Pace A, Giannarelli D, Galiè E, Savarese A, Carpano S, Della Giulia M, et al. Vitamin E neuroprotection for cisplatin neuropathy: A randomized, placebo-controlled trial. Neurology 2010;74:762-6.  Back to cited text no. 13
Saif MW. Oral calcium ameliorating oxaliplatin-induced peripheral neuropathy. J Appl Res 2004;4:576-82.  Back to cited text no. 14
Ishibashi K, Okada N, Miyazaki T, Sano M, Ishida H. Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: A prospective randomized study. Int J Clin Oncol 2010;15:82-7.  Back to cited text no. 15
Gamelin L, Boisdron-Celle M, Delva R, Guérin-Meyer V, Ifrah N, Morel A, et al. Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: A retrospective study of 161 patients receiving oxaliplatin combined with 5-Fluorouracil and leucovorin for advanced colorectal cancer. Clin Cancer Res 2004;10:4055-61.  Back to cited text no. 16
Aksoy N, Aksoy M, Bagci C, Gergerlioglu HS, Celik H, Herken E, et al. Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats. Tohoku J Exp Med 2007;212:43-8.  Back to cited text no. 17
Navis I, Sriganth P, Premalatha B. Dietary curcumin with cisplatin administration modulates tumour marker indices in experimental fibrosarcoma. Pharmacol Res 1999;39:175-9.  Back to cited text no. 18
Serpeloni JM, Grotto D, Mercadante AZ, de Lourdes Pires Bianchi M, Antunes LM. Lutein improves antioxidant defense in vivo and protects against DNA damage and chromosome instability induced by cisplatin. Arch Toxicol 2010;84:811-22.  Back to cited text no. 19
Heys SD, Ogston K, Miller I, Hutcheon AW, Walker LG, Sarker TK, et al. Potentiation of the response to chemotherapy in patients with breast cancer by dietary supplementation with L-arginine: Results of a randomised controlled trial. Int J Oncol 1998;12:221-5.  Back to cited text no. 20
van Wijk N, Rijntjes E, van De Heijning BJ. Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. Exp Physiol 2008;93:1199-209.  Back to cited text no. 21
Shabani M, Nazeri M, Parsania S, Razavinasab M, Zangiabadi N, Esmaeilpour K, et al. Walnut consumption protects rats against cisplatin-induced neurotoxicity. Neurotoxicology 2012;33:1314-21.  Back to cited text no. 22
Razavinasab M, Moazzami K, Shabani M. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 Pyramidal neurons in rat offspring. Toxicol Ind Health 2014. [Epub ahead of print].  Back to cited text no. 23
Shabani M, Larizadeh MH, Parsania S, Hajali V, Shojaei A. Evaluation of destructive effects of exposure to cisplatin during developmental stage: No profound evidence for sex differences in impaired motor and memory performance. Int J Neurosci 2012;122:439-48.  Back to cited text no. 24
Haghani M, Shabani M, Moazzami K. Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring. Neuroscience 2013;250:588-98.  Back to cited text no. 25
Razavinasab M, Shamsizadeh A, Shabani M, Nazeri M, Allahtavakoli M, Asadi-Shekaari M, et al. Pharmacological blockade of TRPV1 receptors modulates the effects of 6-OHDA on motor and cognitive functions in a rat model of Parkinson's disease. Fundam Clin Pharmacol 2013;27:632-40.  Back to cited text no. 26
Frick KM, Stillner ET, Berger-Sweeney J. Mice are not little rats: Species differences in a one-day water maze task. Neuroreport 2000;11:3461-5.  Back to cited text no. 27
Parsania S, Shabani M, Moazzami K, Razavinasab M, Larizadeh MH, Nazeri M, et al. Gender difference in motor impairments induced by chronic administration of vinblastine. Iran J Basic Med Sci 2014;17:433-40.  Back to cited text no. 28
Hajali V, Sheibani V, Esmaeili-Mahani S, Shabani M. Female rats are more susceptible to the deleterious effects of paradoxical sleep deprivation on cognitive performance. Behav Brain Res 2012;228:311-8.  Back to cited text no. 29
Zangiabadi N, Asadi-Shekaari M, Sheibani V, Jafari M, Shabani M, Asadi AR, et al. Date fruit extract is a neuroprotective agent in diabetic peripheral neuropathy in streptozotocin-induced diabetic rats: A multimodal analysis. Oxid Med Cell Longev 2011;2011:976948.  Back to cited text no. 30
Rzeski W, Pruskil S, Macke A, Felderhoff-Mueser U, Reiher AK, Hoerster F, et al. Anticancer agents are potent neurotoxins in vitro and in vivo. Ann Neurol 2004;56:351-60.  Back to cited text no. 31
Shabani M, Larizadeh MH, Parsania S, Asadi Shekaari M, Shahrokhi N. Profound destructive effects of adolescent exposure to vincristine accompanied with some sex differences in motor and memory performance. Can J Physiol Pharmacol 2012;90:379-86.  Back to cited text no. 32
Avella D, Pisu MB, Roda E, Gravati M, Bernocchi G. Reorganization of the rat cerebellar cortex during postnatal development following cisplatin treatment. Exp Neurol 2006;201:131-43.  Back to cited text no. 33
Pisu MB, Roda E, Guioli S, Avella D, Bottone MG, Bernocchi G. Proliferation and migration of granule cells in the developing rat cerebellum: Cisplatin effects. Anat Rec A Discov Mol Cell Evol Biol 2005;287:1226-35.  Back to cited text no. 34
Wick A, Wick W, Hirrlinger J, Gerhardt E, Dringen R, Dichgans J, et al. Chemotherapy-induced cell death in primary cerebellar granule neurons but not in astrocytes: In vitro paradigm of differential neurotoxicity. J Neurochem 2004;91:1067-74.  Back to cited text no. 35
Hill A, Bergin P, Hanning F, Thompson P, Findlay M, Damianovich D, et al. Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability. BMC Cancer 2010;10:451.  Back to cited text no. 36
Varadinova MG, Docheva-Drenska DI, Boyadjieva NI. Effects of anthocyanins on learning and memory of ovariectomized rats. Menopause 2009;16:345-9.  Back to cited text no. 37
Dreiseitel A, Schreier P, Oehme A, Locher S, Rogler G, Piberger H, et al. Inhibition of proteasome activity by anthocyanins and anthocyanidins. Biochem Biophys Res Commun 2008;372:57-61.  Back to cited text no. 38
Garcia-Alonso M, Rimbach G, Sasai M, Nakahara M, Matsugo S, Uchida Y, et al. Electron spin resonance spectroscopy studies on the free radical scavenging activity of wine anthocyanins and pyranoanthocyanins. Mol Nutr Food Res 2005;49:1112-9.  Back to cited text no. 39
Marko D, Puppel N, Tjaden Z, Jakobs S, Pahlke G. The substitution pattern of anthocyanidins affects different cellular signaling cascades regulating cell proliferation. Mol Nutr Food Res 2004;48:318-25.  Back to cited text no. 40
Bickford PC, Shukitt-Hale B, Joseph J. Effects of aging on cerebellar noradrenergic function and motor learning: Nutritional interventions. Mech Ageing Dev 1999;111:141-54.  Back to cited text no. 41
Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 1999;19:8114-21.  Back to cited text no. 42
Saija A, Princi P, D'Amico N, De Pasquale R, Costa G. Effect of Vaccinium myrtillus anthocyanins on triiodothyronine transport into brain in the rat. Pharmacol Res 1990;22(Suppl 3):59-60.  Back to cited text no. 43
McEntee WJ, Crook TH. Glutamate: Its role in learning, memory, and the aging brain. Psychopharmacology (Berl) 1993;111:391-401.  Back to cited text no. 44
Spencer JP. Food for thought: The role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc Nutr Soc 2008;67:238-52.  Back to cited text no. 45
Haque R, Bin-Hafeez B, Parvez S, Pandey S, Sayeed I, Ali M, et al. Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide-induced biochemical toxicity. Hum Exp Toxicol 2003;22:473-80.  Back to cited text no. 46
Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, et al. Green tea consumption and cognitive function: A cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr 2006;83:355-61.  Back to cited text no. 47
Viggiano A, Viggiano A, Monda M, Turco I, Incarnato L, Vinno V, et al. Annurca apple-rich diet restores long-term potentiation and induces behavioral modifications in aged rats. Exp Neurol 2006;199:354-61.  Back to cited text no. 48
Wang Y, Wang L, Wu J, Cai J. The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats. Br J Pharmacol 2006;148:147-53.  Back to cited text no. 49
Rajaei A, Barzegar M, Mobarez AM, Sahari MA, Esfahani ZH. Antioxidant, anti-microbial and antimutagenicity activities of pistachio (Pistachia vera) green hull extract. Food Chem Toxicol 2010;48:107-12.  Back to cited text no. 50
Khasabova IA, Khasabov S, Paz J, Harding-Rose C, Simone DA, Seybold VS. Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy. J Neurosci 2012;32:7091-101.  Back to cited text no. 51
Gregg RW, Molepo JM, Monpetit VJ, Mikael NZ, Redmond D, Gadia M, et al. Cisplatin neurotoxicity: The relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity. J Clin Oncol 1992;10:795-803.  Back to cited text no. 52