Cadmium (Cd) is one of the environmental pollutants affecting various tissues and organs including testis. The aim of this study was to investigate the anti-apoptotic effects of curcumin (Cur) on Cd-induced apoptosis in rat testes. The rats were randomly allotted into one of three experimental groups: control, Cd treated and Cd treated with Cur; each group contained 10 animals. The control group received 2 ml/day of dimethyl sulfoxide (DMSO). To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 4 weeks. The rats in Cur-treated group was given a daily dose of 100 mg/kg of Cur for 4 weeks. To date, no examinations of the anti-apoptotic properties of Cur on Cd-induced apoptosis in rat testes have been reported. The mean seminiferous tubule diameter, mean testicular biopsy score values and serum testosterone levels were significantly decreased in Cd-treated groups were compared to the control group. Furthermore, the Cur-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in testis tissues of the Cd-treated group with Cur therapy. The present study showed that Cur treatment protected testes against toxic effects of Cd. We believe that further preclinical research into the utility of Cur may indicate its usefulness as a potential treatment on the spermatogenesis after testicular injury caused by Cd-treated rats.
AfonneOJOrisakweOEEkanemIA (2002) Zinc protects chromium-induced testicular injury in mice. Indian Journal of Pharmacology34: 26–31.
2.
AktasCKanterM (2009) A morphological study on Leydig cells of scrotal hyperthermia applied rats in short-term. Journal of Molecular Histology40: 31–39.
3.
AmaraSAbdelmelekHGarrelC. (2007) Preventive effect of zinc against cadmium induced oxidative stress in the rat testis. Journal of Reproduction and Development20:/1–15.
4.
BatraNNehruBBansalMP (1998) The effects of zinc supplementation on the effects of lead on the rat testis. Reproductive Toxicology12: 535–540.
5.
Blanco-RodriguezJMartinez-GarciaC (1998) Apoptosis precedes detachment of germ cells from the seminiferous epithelium after hormonal suppression by short-term oestradiol treatment of rats. International Journal of Andrology21: 109–115.
6.
BrzoskaMMJakoniukJM (2001) Interactions between cadmium and zinc in the organism. Food and Chemical Toxicology39: 967–980.
7.
BrzoskaMMJakoniukJMJurczukM. (2001) The effect of zinc supply on cadmium-induced changes in the tibia of rats. Food and Chemical Toxicology39: 729–737.
8.
ChenJTangXQZhiJL. (2006) Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ioninduced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway. Apoptosis11: 943–953.
9.
ClaveriaCCorbellaRMartinD. (2000) Protective effects of zinc on cadmium toxicity in rodents. Biological Trace Element Research75: 1–3.
10.
DiemerTAllenJAHalesKHHalesDB (2003) Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology144: 2882–2891.
11.
El-DemerdashFMYousefMIRadwanFM (2009) Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs. Food and Chemical Toxicology47(1): 249–254.
12.
FarombiEOAbarikwuSOAdedaraIAOyeyemiMO (2007) Curcumin and kolaviron ameliorate di-n-butylphthalate-induced tesicular damage in rats. Basic & Clinical Pharmacology & Toxicology100: 43–8.
13.
GiannessiFGiambellucaMAGrassoL. (2008) Curcumin protects Leydig cells of mice from damage induced by chronic alcohol administration. Medical Science Monitor14(11): 237–242.
14.
GoyerRALiuJWaalkesMP (2004) Cadmium and cancer of prostate and testis. Biometals17:/555–558.
15.
GunnarssonDNordbergGSelstamG (2007) Differential effects of cadmium on the gene expression of seventransmembrane-spanning receptors and GAPDH in the rat testis. Toxicology Letters168(1): 51–57.
16.
HammondPBFoulkesEC (1986) Metal ion toxicity in man and animals. In: SigelH (ed.) Metals Ions in Biological Systems. New York: Marcel Dekker, 20, 157–200.
17.
HassoumEAStohsSJ (1996) Cadmium-induced production of superoxide anion and nitric oxide, DNA single strand breaks and lactate dehydrogenase leakage in J774A.1 cell cultures. Toxicology112(3): 219–226.
18.
HuJHJiangJMaYH. (2003) Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas ligand. Cell Research13: 361–367.
19.
IlbeyYOOzbekECekmenMSimsekAOtunctemurASomayA (2009) Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. Human Reproduction24(7): 1717–1725.
20.
JimiSUchiyamaMTakakiA. (2004) Mechanisms of cell death induced by cadmium and arsenic. Annals of the New York Academy of Sciences1011: 325–321.
21.
JohnsenSG (1970) Testicular biopsy score count—a method for registration of spermatogenesis in human testes. Normal values and results of 335 hypogonadal males. Hormones1: 2–25.
22.
JonesMMXuCYLaddPA (1997) Selenite suppression of cadmiuminduced testicular apoptosis. Toxicology116: 169–175.
23.
KalpanaCMenonVP (2004) Curcumin ameliorates oxidative stress during nicotine induced lung toxicity in Wistar rats. Italian Jouranl of Biochemistry53: 82–86.
24.
KlaassenCDLiuJChoudhuriS (1999) Metallothionein: an intracellular protein to protect against cadmium toxicity. Annual Review of Pharmacology and Toxicology39: 267–294.
25.
LaskeyJWPhelpsPV (1991) Effect of cadmium and other metal cations on in vitro leydig cell testosterone production. Toxicology and Applied Pharmacology108: 296–306.
26.
MancaDRicardACTrottierB. (1991) Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride. Toxicology67: 303–323.
27.
MathuriaNVermaRJ (2007) Curcumin ameliorates aflatoxin-induced lipid peroxidation inliver, kidney and testis of mice-an in vitro study. Acta Poloniae Pharmaceutica64(5): 413–416.
28.
NandiSBanerjeePPZirkinBR (1999) Germ cell apoptosis in the testes of Sprague Dawley rats following testosterone withdrawal by ethane 1, 2-dimethanesulfonate administration: relationship to FAS?Biology of Reproduction61: 70–75.
29.
PatrickL (2003) Toxic metals and antioxidants: part II, the role of antioxidants in arsenic and cadmium toxicity. Alternative Medicine Review8: 106–128.
30.
Perez-ArriagaLMendoza-MaganaMLCortes-ZarateR. (2006) Cytotoxic effect of curcumin on Giardia lamblia trophozoites. Acta Tropica98: 152–161.
31.
PolasaKNaiduNARavindranathIKrishanaswamyK (2004) Inhibition of B(a)P induced strand breaks in presence of curcumin. Mutation Research557: 203–213.
32.
RahmanIBiswasSKKirkhamPA (2006) Regulation of inflammation and redox signaling by dietary polyphenols. Biochemical Pharmacology72: 1439–1452.
33.
RamsewakRSDeWittDLNairMG (2000) Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins IIII from Curcuma longa. Phytomedicine7: 303–308.
34.
ReddyACPLokeshBR (1994) Studies on the inhibitory effect of curcumin and euganol on the formation of reactive species and the oxidation of ferrous iron. Molecular and Cellular Biochemistry137: 1–8.
35.
SarkarSYadavPTrivediR. (1995) Cadmium-induced lipid peroxidation and the status of the antioxidant system in rat tissues. Journal of Trace Elements in Medicine and Biology9: 144–149.
36.
SatohMKoyamaHKajiT. (2002) Perspectives on cadmium toxicity research. The Tohoku Journal of Experimental Medicine196: 23–32.
37.
SaxenaSKMurthyRCSinghC. (1989) Zinc protects testicular injury induced by concurrent exposure to cadmium and lead in rats. Research Communications in Chemical Pathology & Pharmacology64: 317–329.
38.
Sen GuptaRKimJGomesC. (2004) Effect of ascorbic acid supplementation on testicular steroidogenesis and germ cell death in cadmium-treated male rats. Molecular and Cellular Endocrinology221(1–2): 57–66.
39.
Sinha-HikimAPSwerdloffRS (1999) Hormonal and genetic control of germ cell apoptosis in the testis. Reviews of Reproduction4: 38–47.
40.
SreejayanNRaoMN (1996) Free radical scavenging activity of curcuminoids. Arzneimittelforschung46: 169–171.
41.
TirkeyNKaurGVijG. (2005) Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys. BMC Pharmacology5: 15.
42.
WaalkesMP (2000) Cadmium Carcinogenesis in review. Journal of Inorganic Biochemistry79: 241–244.
43.
WeiSMYanZZZhouJ (2009) Curcumin attenuates ischemia-reperfusion injury in rat testis. Fertility and Sterility91(1): 271–277.
44.
XuLCSunHWangS. (2005) The roles of metallothionein on cadmium-induced testes damages in Sprage-Dawley rats. Environmental Toxicology and Pharmacology20: 83–87.
45.
XuCJohnsonJESinghPK. (1996) In vivo studies of cadmium-induced apoptosis in testicular tissue of the rat and its modulation by a chelating agent. Toxicology107: 1–8.
46.
YangJMArnushMChenQY. (2003) Cadmium-induced damage to primary cultures of rat Leydig cells. Reproductive Toxicology142: 553–556.
47.
YiinSJChernCLSheuJYLinTH (1999) Cadmium induced lipid peroxidation in rat testes and protection by selenium. Biometals12: 353–359.
48.
ZhouTZhouGSongW. (1999) Cadmium-induced apoptosis and change in expression of p53, c-jun and MT-I genes in testes and ventral prostate of rats. Toxicology142: 1–13.
