Ahmed-Farid, Omar AHNasr, MahaAhmed, Rania FBakeer, Rofanda M2019-10-272019-10-272017-12Herbert DC. Growth patterns and hormonal profile of male rats with protein-calorie malnutrition. Anat Rec. 1980;197(3):339–54. CAS Article PubMed Google Scholar 2. Muzi-Filho H, Bezerra CG, Souza AM, Boldrini LC, Takiya CM, Oliveira FL, et al. Undernutrition affects cell survival, oxidative stress, Ca2+ handling and signaling pathways in vas deferens, crippling reproductive capacity. PLoS One. 2013;8(7):e69682. CAS Article PubMed PubMed Central Google Scholar 3. Carvalho M, Mateus L, Afonso F, Van Harten S, Cardoso LA, Redmer DA, et al. Testicular angiogenic activity in response to food restriction in rabbits. Reproduction. 2009;137(3):509–15. CAS Article PubMed Google Scholar 4. Reyes-Gordillo, K, J Segovia, M Shibayama, P Vergara, MG Moreno, P Muriel. Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress. Biochim Biophys Acta 2007;1770(6):989-996. 5. Sanmukhani J, Anovadiya A, Tripathi CB. Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study. Acta Pol Pharm. 2011;68(5):769–75. CAS PubMed Google Scholar 6. Rashid K, Sil PC. Curcumin ameliorates testicular damage in diabetic rats by suppressing cellular stress-mediated mitochondria and endoplasmic reticulum-dependent apoptotic death. Biochim Biophys Acta. 2015;1852(1):70–82. CAS Article PubMed Google Scholar 7. Yan X, Pan B, Lv T, Liu L, Zhu J, Shen W, et al. Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis. J Biomed Sci. 2017;24(1):1. Article PubMed PubMed Central Google Scholar 8. Lu WP, Mei XT, Wang Y, Zheng YP, Xue YF, Xu DH. Zn(II)-curcumin protects against oxidative stress, deleterious changes in sperm parameters and histological alterations in a male mouse model of cyclophosphamide-induced reproductive damage. Environ Toxicol Pharmacol. 2015;39(2):515–24. CAS Article PubMed Google Scholar 9. Huang H, Chen X, Li D, He Y, Li Y, Du Z, et al. Combination of alpha-Tomatine and Curcumin inhibits growth and induces apoptosis in human prostate cancer cells. PLoS One. 2015;10(12):e0144293. Article PubMed PubMed Central Google Scholar 10. Mehanny M, Hathout RM, Geneidi AS, Mansour S. Exploring the use of nanocarrier systems to deliver the magical molecule; Curcumin and its derivatives. J Control Release. 2016;225:1–30. CAS Article PubMed Google Scholar 11. Onoue S, Takahashi H, Kawabata Y, Seto Y, Hatanaka J, Timmermann B, et al. Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability. J Pharm Sci. 2010;99(4):1871–81. CAS Article PubMed Google Scholar 12. Lin W, Hong JL, Shen G, Wu RT, Wang Y, Huang MT, et al. Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition. Biopharm Drug Dispos. 2011;32(2):65–75. Article PubMed Google Scholar 13. Nasr M. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery. Drug Deliv. 2016;23(4):1444–52. CAS Article PubMed Google Scholar 14. Nasr M, Nawaz S, Elhissi A. Amphotericin B lipid nanoemulsion aerosols for targeting peripheral respiratory airways via nebulization. Int J Pharm. 2012;436(1–2):611–6. CAS Article PubMed Google Scholar 15. Li X, Rezaei R, Li P, Wu G. Composition of amino acids in feed ingredients for animal diets. Amino Acids. 2011;40(4):1159–68. CAS Article PubMed Google Scholar 16. Guo QY, He LX, Zhu H, Shang JL, Zhu LY, Wang JB, et al. Effects of 90-day feeding of transgenic maize BT799 on the reproductive system in male Wistar rats. Int J Environ Res Public Health. 2015;12(12):15309–20. CAS Article PubMed PubMed Central Google Scholar 17. Kim, SK, H Seok, HJ Park, HS Jeon, SW Kang, BC Lee, et al. Inhibitory effect of curcumin on testosterone induced benign prostatic hyperplasia rat model. BMC Complement Altern Med. 2015;15:380. 18. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010. 19. Mohammadi Roushandeh A, Salehi I, Mortazavi M. Protective effects of restricted diet and antioxidants on testis tissue in rats fed with high-fat diet. Iran Biomed J. 2015;19(2):96–101. PubMed PubMed Central Google Scholar 20. Heidari R, Alizadeh R, Abbasi N, Pasbakhsh P, Hedayatpour A, Farajpour M, et al. Do Pilea Microphylla improve sperm DNA fragmentation and sperm parameters in Varicocelized rats? Acta Med Iran. 2015;53(9):547–54. PubMed Google Scholar 21. Seed J, Chapin RE, Clegg ED, Dostal LA, Foote RH, Hurtt ME, et al. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. ILSI risk science institute expert working group on sperm evaluation. Reprod Toxicol. 1996;10(3):237–44. CAS Article PubMed Google Scholar 22. Saunders JA, Saunders JM, Morris S, Wynne SA II. Amino acid analysis of subcellular fractions by pitc and opa. Chromatogram. 1988;9(1):2–4. CAS Google Scholar 23. Yoshida T. Determination of reduced and oxidized glutathione in erythrocytes by high-performance liquid chromatography with ultraviolet absorbance detection. J Chromatogr B Biomed Appl. 1996;678(2):157–64. CAS Article PubMed Google Scholar 24. Jayatilleke E, Shaw S. A high-performance liquid chromatographic assay for reduced and oxidized glutathione in biological samples. Anal Biochem. 1993;214(2):452–7. CAS Article PubMed Google Scholar 25. Karatas F, Karatepe M, Baysar A. Determination of free malondialdehyde in human serum by high-performance liquid chromatography. Anal Biochem. 2002;311(1):76–9. CAS Article PubMed Google Scholar 26. Lazzarino G, Di Pierro D, Tavazzi B, Cerroni L, Giardina B. Simultaneous separation of malondialdehyde, ascorbic acid, and adenine nucleotide derivatives from biological samples by ion-pairing high-performance liquid chromatography. Anal Biochem. 1991;197(1):191–6. CAS Article PubMed Google Scholar 27. Karatepe M. Simultaneous determination of ascorbic acid and free malondialdehyde in human serum by HPLC–UV. LCGC ASIA PACIFIC. 2004;7(2):36–8. Google Scholar 28. Papadoyannis IN, Samanidou VF, Nitsos CC. Simultaneous determination of nitrite and nitrate in drinking water and human serum by high performance anion-exchange chromatography and uv detection. J Liq Chromatogr Relat Technol. 1999;22(13):2023–41. CAS Article Google Scholar 29. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6. CAS Article PubMed Google Scholar 30. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47(3):469–74. CAS Article PubMed Google Scholar 31. Lodovici M, Casalini C, Briani C, Dolara P. Oxidative liver DNA damage in rats treated with pesticide mixtures. Toxicology. 1997;117(1):55–60. CAS Article PubMed Google Scholar 32. Teerlink T, Hennekes M, Bussemaker J, Groeneveld J. Simultaneous determination of creatine compounds and adenine nucleotides in myocardial tissue by high-performance liquid chromatography. Anal Biochem. 1993;214(1):278–83. CAS Article PubMed Google Scholar 33. Liu, H, Y Jiang, Y Luo, W Jiang. A Simple and Rapid Determination of ATP, ADP and AMP Concentrations in Pericarp Tissue of Litchi Fruit by High Performance Liquid Chromatography. Food Technol Biotechnol 2006;44(4):531-534. 34. Atkinson DE, Walton GM. Adenosine triphosphate conservation in metabolic regulation. Rat liver citrate cleavage enzyme. J Biol Chem. 1967;242(13):3239–41. CAS PubMed Google Scholar 35. Tu, L, L Yu, H Zhang. Morphology of rat testis preserved in three different fixatives. J Huazhong Univ Sci Technolog Med Sci 2011;31(2):178-180. 36. Mushtaq H, Alam S, Khan M. Histopathological patterns of testicular biopsies in male infertility. J Islamabad Med Dent Coll (JIMDC). 2013;2(4):81–6. Google Scholar 37. Ono T, Takada S, Kinugawa S, Tsutsui H. Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination. Exp Physiol. 2015;100(9):1052–63. CAS Article PubMed Google Scholar 38. Takhtfooladi MA, Asghari A, Takhtfooladi HA, Shabani S. The protective role of curcumin on testicular tissue after hindlimb ischemia reperfusion in rats. Int Urol Nephrol. 2015;47(10):1605–10. CAS Article PubMed Google Scholar 39. Lonare M, Kumar M, Raut S, More A, Doltade S, Badgujar P, et al. Evaluation of ameliorative effect of curcumin on imidacloprid-induced male reproductive toxicity in wistar rats. Environ Toxicol. 2016;31(10):1250–63. CAS Article PubMed Google Scholar 40. Aktas C, Kanter M, Erboga M, Ozturk S. Anti-apoptotic effects of curcumin on cadmium-induced apoptosis in rat testes. Toxicol Ind Health. 2012;28(2):122–30. CAS Article PubMed Google Scholar 41. Nutrient Requirements of Laboratory Animals: Fourth Revised Edition, 1995. Washington (DC). 42. Clarke, HE, ME Coates, JK Eva, DJ Ford, CK Milner, PN O'Donoghue, et al. Dietary standards for laboratory animals: report of the laboratory animals Centre diets advisory committee. Lab Anim 1977;11(1):1-28. 43. Dong HJ, Wu D, Xu SY, Li Q, Fang ZF, Che LQ, et al. Effect of dietary supplementation with amino acids on boar sperm quality and fertility. Anim Reprod Sci. 2016;172:182–9. CAS Article PubMed Google Scholar 44. van Zutphen T, Ciapaite J, Bloks VW, Ackereley C, Gerding A, Jurdzinski A, et al. Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction. J Hepatol. 2016;65(6):1198–208. Article PubMed Google Scholar 45. Ziolkowski, N,AK Grover. Functional linkage as a direction for studies in oxidative stress: alpha-adrenergic receptors. Can J Physiol Pharmacol 2010;88(3):220-232. 46. Ghone RA, Suryakar AN, Kulhalli PM, Bhagat SS, Padalkar RK, Karnik AC, et al. A study of oxidative stress biomarkers and effect of oral antioxidant supplementation in severe acute malnutrition. J Clin Diagn Res. 2013;7(10):2146–8. PubMed PubMed Central Google Scholar 47. Freitas I, Boncompagni E, Tarantola E, Gruppi C, Bertone V, Ferrigno A, et al. In situ evaluation of oxidative stress in rat fatty liver induced by a Methionine- and Choline-deficient diet. Oxidative Med Cell Longev. 2016;2016:9307064. Google Scholar 48. Ahmed-Farid, O, R Ahmed, D Saleh. Combination of resveratrol and fluoxetine in an acute model of depression in mice: Prevention of oxidative DNA fragmentation and monoamines degradation. J Appl Pharm Sci. 2016:001–7. 49. Suski JM, Lebiedzinska M, Bonora M, Pinton P, Duszynski J, Wieckowski MR. Relation between mitochondrial membrane potential and ROS formation. Methods Mol Biol. 2012;810:183–205. CAS Article PubMed Google Scholar 50. Jorgacevic B, Mladenovic D, Ninkovic M, Prokic V, Stankovic MN, Aleksic V, et al. Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Hum Exp Toxicol. 2014;33(7):701–9. CAS Article PubMed Google Scholar 51. Lee SJ, Kang JH, Iqbal W, Kwon OS. Proteomic analysis of mice fed methionine and choline deficient diet reveals marker proteins associated with steatohepatitis. PLoS One. 2015;10(4):e0120577. Article PubMed PubMed Central Google Scholar 52. Stankovic MN, Mladenovic D, Ninkovic M, Ethuricic I, Sobajic S, Jorgacevic B, et al. The effects of alpha-lipoic acid on liver oxidative stress and free fatty acid composition in methionine-choline deficient diet-induced NAFLD. J Med Food. 2014;17(2):254–61. CAS Article PubMed PubMed Central Google Scholar 53. Juyena NS, Stelletta C. Seminal plasma: an essential attribute to spermatozoa. J Androl. 2012;33(4):536–51. Article PubMed Google Scholar 54. Yang J, Wu G, Feng Y, Lv Q, Lin S, Hu J. Effects of taurine on male reproduction in rats of different ages. J Biomed Sci. 2010;17(Suppl 1):S9. Article PubMed PubMed Central Google Scholar 55. Dhawan K, Kumar S, Sharma A. Beneficial effects of chrysin and benzoflavone on virility in 2-year-old male rats. J Med Food. 2002;5(1):43–8. CAS Article PubMed Google Scholar 56. Gao F, Zhang Z, Bu H, Huang Y, Gao Z, Shen J, et al. Nanoemulsion improves the oral absorption of candesartan cilexetil in rats: performance and mechanism. J Control Release. 2011;149(2):168–74. CAS Article PubMed Google Scholar 57. Salvia-Trujillo L, Martin-Belloso O, McClements DJ. Excipient Nanoemulsions for improving oral bioavailability of bioactives. Nanomaterials (Basel). 2016;6(1):17.1423-0127https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-017-0373-5Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats. Juvenile rats were fed the protein deficient diet (PDD) for 75 days. Starting from day 60 the rats were divided into 4 groups and given the corresponding treatments for the last 15 days orally and daily as follows: 1st group; curcumin group (C) received 50 mg/kg curcumin p.o. 2ndgroup; curcumin nano-form low dose group (NCL) received 2.5 mg/kg nano-curcumin. 3rd group; curcumin nano-form high dose group (NCH) received 5 mg/kg nano-curcumin. 4th group served as malnutrition group (PDD group) receiving the protein deficient diet daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. A normal control group was kept under the same conditions for the whole experiment and received normal diet according to nutrition requirement center daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. PDD induced significant (P < 0.05) reduction in serum testosterone level, sperm motility, testicular GSH, CAT, SOD, testicular cell energy (ATP, ADP and AMP), essential and non-essential amino acids in seminal plasma, an increase in testicular MDA, NOx, GSSG and 8-OHDG. Data was …en-USProtein deficient dietCurcuminMale fertilityNano-curcuminArticle