Cisplatin (CP), an effective anticancer agent, carries the risk of impairing testicular function leading to infertility. The present study aimed at evaluating the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP-induced oxidative stress and testicular injuries in rats.
Rats were divided into six groups (n = 6). Group I (control), group II (CP single dose on day 16). Group III received AHE for 21 days. Group IV (CP + AHE; post- treatment group). Group V (AHE + CP; pre-treatment group) and group VI (CP + Sily).
CP treatment reduced serum testosterone (T), LH and FSH, decreased the activity level of antioxidant enzymes while increased the concentration of oxidative stress markers, i.e. thiobarbituric acid reactive substances (TBARS), H2O2 and nitric oxide (NO) along with corresponding DNA damages. Furthermore, CP induced adverse morphological changes in testis of rats including reduced epithelial height and tubular diameter, increased luminal diameter with impaired spermatogenesis. Pre and post-treatment with AHE reduced the side effects of CP in testis tissues through improvement in the reproductive hormonal secretions, enzymatic activities, histological and DNA damage parameters. Pretreatment seems to be more effective and equivalent to silymarin group in reversing the CP deleterious effects as compared to post-treatment.
The results demonstrated that A. hydaspica treatment in CP-induced testicular toxicity augments the antioxidants defense mechanism, reverted the level of fertility hormones, suppressed the histomorphological alterations and DNA damages and thus provides the evidence that it may have a therapeutic role in free radical mediated diseases.
Yildirim NC, Kandemir FM, Benzer F. Beneficial effects of grape seed extract against cisplatin-induced testiculer damage in rabbits. Dig J Nanomater Biostruct. 2011;6(1):155–9.
Huleihel M, Lunenfeld E. Regulation of spermatogenesis by paracrine/autocrine testicular factors. Asian J Androl. 2004;6(3):259–68. PubMed
Meistrich ML, Finch M, da Cunha MF, Hacker U, WW A. Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells. Cancer Res. 1982;42(1):122–31. PubMed
Lirdi LC, Stumpp T, Sasso-Cerri E, Miraglia SM. Amifostine protective effect on cisplatin-treated rat testis. Anat Rec. 2008;291(7):797–808. CrossRef
Shah NA, Khan MR, Naz K, khan MA. antioxidant potential, DNA protection, and HPLC-DAD analysis of neglected medicinal Jurinea dolomiaea roots. Biomed Res Int. 2014;2014
HemaIswarya S, Doble M. Potential synergism of natural products in the treatment of cancer. Phytother Res. 2006;20(4):239–49.
Seigler DS. Phytochemistry of Acacia—Sensu Lato. Biochem Syst Ecol. 2003;31(8):845–73. CrossRef
Duarte MR, Wolf S. Anatomical characters of the phyllode and stem of Acacia podalyriifolia A. Cunn. ex G. Don (Fabaceae). Rev Bras. 2005;15(1):71–6.
Chakrabarty T, Gangopadhyay M. The genus acacia P. Miller (Leguminosae: Mimosoideae) in India. J Econ Taxon Bot. 1996;20(3):599–633.
Afsar T, Razak S, Khan MR, Mawash S, Almajwal A, Shabir M, Haq IU. Evaluation of antioxidant, anti-hemolytic and anticancer activity of various solvent extracts of Acacia Hydaspica R. Parker aerial parts. BMC Complement Altern Med. 2016;16(1):258.
Ojha S, Al Taee H, Goyal S, Mahajan UB, Patil CR, Arya D, Rajesh M. Cardioprotective potentials of plant-derived small molecules against doxorubicin associated cardiotoxicity.Oxid Med Cell Longev 2016;2016:5724973.
Kranti V, Mahesh V, Srinivas P, Ganesh Y, Godwin A, Lahkar M. Evaluation of the protective effect of silymarin on doxorubicin induced chronic testicular toxicity in rats. Int J Pharm Bio Sci. 2013;4(1):473–84.
Afsar T, Khan MR, Razak S, Ullah S, Mirza B. Antipyretic, anti-inflammatory and analgesic activity of Acacia Hydaspica R. Parker and its phytochemical analysis. BMC Complement Altern Med. 2015;15(1):1. CrossRef
Guideline OO. 425: acute oral toxicity—up-and-down procedure. Paris: OECD Guidelines for the Testing of Chemicals Organization for Economic Cooperation and Development; 2001.
Turner P, Granville-Grossman K, Smart J. Effect of adrenergic receptor blockade on the tachycardia of thyrotoxicosis and anxiety state. Lancet. 1965;286(7426):1316–8. CrossRef
Guideline OO. 425: acute oral toxicity—up-and-down procedure. OECD Guidelines for the Testing of Chemicals. 2001;2:12–6.
Irwin S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacology. 1968;13(3):222–57. CrossRef
Mensah A, Mireku E, Mensah M, Amponsah I. Some neurological effects of the ethanolic stem bark extract of Cussonia bancoensis Aubrev and Pellgr (Araliaceae). Journal of Pharmacognosy and Phytochemistry. 2014;2(6):101–6.
Mohamed MM. Garlic powder attenuates acrylamide-induced oxidative damage in multiple organs in rat. J Appl Sci Res. 2012;8(1):168–73.
Chance B, Maehly A:  assay of catalases and peroxidases. 1955. CrossRef
Kakkar P, Das B, Viswanathan P. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984;21(2):130–2. PubMed
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-Transferases the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130–9. PubMed
Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem. 1975;250(14):5475–80. PubMed
Iqbal S, Bhanger M, Anwar F. Antioxidant properties and components of some commercially available varieties of rice bran in Pakistan. Food Chem. 2005;93(2):265–72. CrossRef
Jensen EC. Quantitative analysis of histological staining and fluorescence using ImageJ. Anat Rec. 2013;296(3):378–81. CrossRef
Sawhney P, Giammona CJ, Meistrich ML, Richburg JH. Cisplatin-induced long-term failure of spermatogenesis in adult C57/Bl/6J mice. J Androl. 2005;26(1):136–45. PubMed
Latif R, Lodhi GM, Aslam M. Effects of amlodipine on serum testosterone, testicular weight and gonado-somatic index in adult rats. J Ayub Med Coll Abbottabad. 2008;20(4):8–10. PubMed
Azu OO, Duru FI, Osinubi AA, Noronha CC, Elesha SO, Okanlawon AO. Protective agent, Kigelia Africana fruit extract, against cisplatin-induced kidney oxidant injury in Sprague–Dawley rats. Asian J Pharma Clin Res. 2010;3(2):84–8.
Manna P, Sinha M, Sil PC. Aqueous extract of Terminalia Arjuna prevents carbon tetrachloride induced hepatic and renal disorders. BMC Complement Altern Med. 2006;6(1):1. CrossRef
MD MAINES, PM SLUSS, ISCAN M. Cis-platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors and cytochrome P-450scc in rat testis*. Endocrinology. 1990;126(5):2398–406. CrossRef
Ilbey YO, Ozbek E, Cekmen M, Simsek A, Otunctemur A, Somay A. Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. Hum Reprod. 2009;24(7):1717–25.
Brilhante O, Stumpp T, Miraglia S. Long-term testicular toxicity caused by doxorubicin treatment during pre-pubertal phase. Int J Med Sci. 2011;3(2):52–60.
Hozayen WG. Effect of hesperidin and rutin on doxorubicin induced testicular toxicity in male rats. Int J Food Nutr Sci. 2012;1:31–42.
Chapman R, Rees L, Sutcliffe S, Edwards C, Malpas J. Cyclical combination chemotherapy and gonadal function: retrospective study in males. Lancet. 1979;313(8111):285–9. CrossRef
Patil L, Balaraman R. Effect of melatonin on doxorubicin induced testicular damage in rats. Int J PharmTech Res. 2009;1(3):879–4.
Khaki A, Fathiazad F, Nouri M, Khaki AA, Ozanci CC, Ghafari-Novin M, Hamadeh M. The effects of ginger on spermatogenesis and sperm parameters of rat. Iranian Journal of Reproductive Medicine. 2009;7(1):7–12.
Sridevi T. Effect of doxorubicin on the biochemical activities of the male reproductive system of white mice-Mus Musculus. Indian Journal of Science and Technology. 2011;4(12):1715–20.
Amin A, Abraham C, Hamza AA, Abdalla ZA, Al-Shamsi SB, Harethi SS, Daoud S. A standardized extract of Ginkgo Biloba neutralizes cisplatin-mediated reproductive toxicity in rats. Biomed Res Int. 2012;2012.
- Acacia hydaspica ethyl acetate extract protects against cisplatin-induced DNA damage, oxidative stress and testicular injuries in adult male rats
Muhammad Rashid khan
- BioMed Central
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