Protective role of lycopene on cisplatin-induced changes in sperm characteristics, testicular damage and oxidative stress in rats
Introduction
Chemotherapy has improved the quality of life of cancer patients and given hope for remission. Despite successes, even the most effective anti-cancer drugs may cause unwanted lesions [1], [2], [3]. Cisplatin (cis-diamminedichloroplatinum-II, CP) is a widely prescribed anticancer drug. Activity has been demonstrated against a variety of neoplasm's, particularly in the head and neck, testis and ovary, bladder and small-cell lung cancers. High doses of CP can damage different tissues such as kidney, liver and testes. Impairment of renal function is recognized as the main side effect of CP and the most important dose-limiting factor [4], [5], [6], [7]. In addition, genotoxicity has been shown in different animals by chromosome aberration, sister chromatid exchange and micronucleus assays in bone marrow and spermatogonia. Owing to the relative spermiotoxicity of CP, almost all the human patients show temporary or permanent azoospermia [1], [8], [9], [10], [11], [12].
Pathogenesis of renal, hepatic, testicular damage following CP exposure is generally ascribed to oxidative damage. CP causes lipid peroxidation and decreases the activity of enzymes that protect against oxidative damage in these tissues. The administration of antioxidants such as Vitamin E, selenium, Vitamin C, carotenoids and others may protect against xenobiotic-induced damage [8], [9], [13], [14], [15]. Lycopene, an aliphatic hydrocarbon, is one of the 600 known naturally occurring carotenoids. Recently, lycopene in tomatoes has attracted attention due to efficient antioxidant properties and free radical scavenging capacity [16], [17], [18], [19].
The aims of the present study were to investigate the effects of CP on sperm characteristics, plasma testosterone levels, histopathological and biochemical changes related to oxidative stress in testes and to examine the protective effect of lycopene on these parameters.
Section snippets
Chemicals
Cisplatin (10 mg/10 ml, Code 1876A) was purchased from Faulding Pharmaceuticals Plc (Warwickshire, UK), lycopene 10%FS (Redivivo TM, Code 7803) from DSM Nutritional Products (İstanbul, Turkey). The other chemicals were obtained from Sigma (St. Louis, MO, USA).
Animals and treatments
This study used 24 healthy adult male Sprague–Dawley rats (8 weeks old weighing 190–250 g). The animals were obtained from the Fırat University Medical School, Experimental Research Centre, Elazığ, Turkey. They were kept under standard
Organ weights and dimensions
The values of testis weights and dimensions, epididymis and accessory glands weights are shown in Table 1. A significant difference (p < 0.05) was found in both right and left testes weights between control and other groups. There was a significant difference (p < 0.05) between the control and CP alone group with respect to the lengths of the right and left testes. When the weight of the epididymis was analyzed, all the groups receiving CP had significantly reduced epididymal weights (both right
Discussion
Cisplatin-based chemotherapy results in damage of different tissues such as kidney, liver and testes. Recently, it has attracted more attention owing to impairment in testicular function following the chemotherapy [1], [4], [10], [29], [30]. Ishikawa et al. [29] reported that chemotherapy-induced gonadal toxicity and recovery of spermatogenesis are related to the type of drugs used, their total dose, and the duration of therapy. Some investigators [9], [10], [11], [12] have reported that CP
Acknowledgement
We wish to thank Dr. Aykut Özdarendeli and Dr. Ahmet Ayar for their valuable criticisms on the language of the paper.
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