To investigate a possible protective role of lycopene on adriamycin (ADR)-induced spermiotoxicity using quantitative, biochemical and histopathological approaches.
Firat University Medical School, Experimental Research Centre, Elazig, Turkey.
Twenty four Sprague Dawley rats (8-weeks old)
Adriamycin (10 mg kg(-1)) was intraperitoneally injected and lycopene (4 mg kg(-1)) was administered by gavage in corn oil.
Reproductive organ weights were evaluated along with epididymal sperm concentration, motility and morphology. Testicular histological findings, oxidative status and plasma testosterone levels were also determined.
Lycopene ameliorated ADR-induced reductions in both testes and epididymis weights. ADR decreased sperm motility, increased total abnormal sperm rates, but epididymal sperm concentration was not changed compared to control. A marked normalization was achieved in sperm motility and morphology in pretreatment with lycopene. Although testosterone level was decreased in ADR group compared to control, no changes were observed in pretreatment group. An increase in malondialdehyde and a decrease reduced glutathione concentrations were detected in alone ADR group compared to control. Pretreatment with lycopene restored significantly malondialdehyde and reduced glutathione concentrations. ADR caused severe degenerative changes in germinative cells, atrophy in the diameter size of seminiferous tubules and germinative cell thickness. However, ADR-induced histopathological alterations were effectively reverted by pretreatment with lycopene.
This study clearly indicates that ADR treatment markedly impaired testicular function and that pretreatment with lycopene might prevent this toxicity.
"Lycopene has a protective effect against testicular toxicity (Atessahin et al., 2006a; Turk et al., 2007), spermiotoxicity (Atessahin et al., 2006a, b), cardiotoxicity (Yilmaz et al., 2005), hepatotoxicity and nephrotoxicity (Yilmaz et al., 2005). Very recently we found that lycopene protected Leydig cellular StAR protein and steroidogenic enzyme expression and confirmed its activity against PCBs (Elumalai et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: Sertoli cell proliferation is attenuated before attaining puberty and the number is fixed in adult testes. Sertoli cells determine both testis size and daily sperm production by providing physical and metabolic support to spermatogenic cells. Polychlorinated biphenyls (PCBs) exposure disrupts functions of Sertoli cells causing infertility with decreased sperm count. On the other hand, lycopene is improving sperm count and motility by reducing oxidative stress in humans and animals. Hence we hypothesized that PCBs-induced infertility might be due to Sertoli cell apoptosis mediated by oxidative stress and lycopene might prevent PCBs-induced apoptosis by acting against oxidative stress. To test this hypothesis, animals were treated with vehicle control, lycopene, PCBs and PCBs + lycopene for 30 days. After the experimental period, the testes and cauda epididymidis were removed for isolation of Sertoli cells and sperm, respectively. We observed increased levels of oxidative stress markers (H2O2 and LPO) levels, increased expression of apoptotic molecules (caspase-8, Bad, Bid, Bax, cytochrome C and caspase-3), decreased anti-apoptotic (Bcl2) molecule and elevated apoptotic marker activity (caspase-3) in Sertoli cells of PCBs-exposed animals. These results were associated with decreased sperm count and motility in PCBs exposed animals. On the other hand, lycopene prevented the elevation of Sertoli cellular apoptotic parameters and prevented the reduction of sperm parameters (count and motility). The data confirmed that lycopene as an antioxidant scavenged reactive oxygen substances, prevented apoptosis, maintained normal function in Sertoli cells and helped to provide physical and metabolic support for sperm production, thereby treating infertility in men.
"In addition, it is likely that the dysfunction of the pituitary in LH releasing was resulted from damage to the cell membrane-mediated signaling mechanisms involved in releasing LH. This conclusion is confirmed by the findings that DOX can interact with cell membranes and change biochemical functions of them, without entering the cells (33). So it seems that reduced LH level in our study is resulted from damaged pituitary cell membranes after DOX exposure. "
[Show abstract][Hide abstract] ABSTRACT: Background: Doxorubicin (DOX), an anthracycline antibiotic, is a widely used anticancer agent. In spite of its high antitumor efficacy, the use of DOX in clinical chemotherapy is limited due to diverse toxicities, including gonadotoxicity.
Objective: We investigated the protective effect of nano-zinc oxide (nZnO) as an established antioxidant on DOX-induced testicular disorders.
Materials and Methods: In this experimental study 24 adult male Wistar rats were divided into four groups including one control and three experimentals (6 rats per group). They received saline (as control), DOX alone (6 mg/kg body weight, i.p.), nZnO alone (5 mg/kg body weight, i.p.), and nZnO followed by DOX. Animals were sacrificed 28 days after treatment and evaluations were made by sperm count and measuring sex hormone levels in plasma. Also total antioxidant power (TAP) and lipid peroxidation (LPO) in plasma were tested. Data was analyzed with SPSS-14 and one way ANOVA test. P<0.05 were considered to be statistically significant.
Results: In the DOX-exposed rats significant differences were found compared with the control group (p=0.001) in plasma total antioxidant power (TAP) (425.50±32.33 vs. 493.33±18.54 mmol/mL), Lipid peroxidation (LPO) (3.70±0.44 vs. 2.78±0.68 μmol/mL), plasma testosterone (3.38±0.69 vs. 5.40±0.89 ng/dl), LH (0.26±0.05 vs. 0.49±0.18 mlU/mL), sperm count (157.98±6.29 vs. 171.71±4.42×106/mL) and DNA damage (11.51±3.45 vs. 6.04±2.83%). Co-administration of nZnO significantly improved DOX-induced changes (p=0.013) in plasma TAP (471.83±14.51 mmol/mL), LPO (2.83±0.75 μmol/mL), plasma testosterone (5.00±1.07 ng/dl), LH (0.52±0.08 mlU/mL), sperm count (169.13±5.01×106/mL) and DNA damage (7.00±1.67%).
Conclusion: At the dose designed in the present investigation cytoprotective role of nano-zinc oxide through its antioxidant potential is illuminated in DOX-induced male gonadotoxicity.
Iranian Journal of Reproductive Medicine 05/2013; 11(5):355-64. · 0.19 Impact Factor
"The clinical application of DOX has been largely complicated by its potential toxicity to the various organs including testis (Imahie et al., 1995; Kato et al., 2001). The DOX-induced testicular cytotoxicity appears to be mainly due to overload of oxidative stress, breakage of DNA continuity, and induction of cell apoptosis (Atessahin et al., 2006b). "
[Show abstract][Hide abstract] ABSTRACT: Objective: Doxorubicin (DOX) is a broad spectrum chemotherapeutic agent used in the treatment of several malignancies. The use of DOX in clinical chemotherapy has been restricted due to its diverse toxicities, including reproductive toxicity. Crataegus monogyna (C. monogyna) is one of the oldest medicinal plants that have been shown to be cytoprotective because of scavenging free radicals. The present study was undertaken to determine whether C. monogyna fruits aqueous extract could serve as a protective agent against reproductive toxicity during DOX treatment in a rat model through antioxidant-mediated mechanisms.
Materials and Methods: Male Wistar rats were allocated to four groups. Two groups of rats were treated with DOX at a dose of 4 mg/kg intraperitoneally on days 1, 7, 14, 21, and 28 (accumulated dose of 20 mg/kg). One of the groups received C. monogyna fruits aqueous extract at a dose of 20 mg/kg per day orally for 28 days along with DOX. A vehicle-treated control group and a C. monogyna control group were also included.
Results: The DOX-treated group showed significant decreases in the body and organ weights and spermatogenic activities as well as many histological alterations. DOX treatment also caused a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK, and SGOT were observed in DOX-treated rats. Notably, Crataegus co-administration caused a partial recovery in above-mentioned parameters.
Conclusion: These findings indicated that doxorubicin can adversely damage the testicular tissue, while Crataegus co-administration could effectively prevent these adverse effects by effective inhibiting oxidative processes and restoration of antioxidant defense system.
Avicenna Journal of Phytomedicine 03/2013; 3(2):159-170.
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