Protective role of lycopene on cisplatin-induced changes in sperm characteristics, testicular damage and oxidative stress in rats

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Abstract

The aim of this study was to investigate the possible protective role of lycopene on cisplatin (CP)-induced spermiotoxicity using quantitative, biochemical and histopathological approaches. Adult male Sprague–Dawley rats were randomly divided into four groups. The control group received physiological saline; animals in cisplatin group received only cisplatin; pre-treatment group received a 10-day of lycopene before administration of cisplatin while animals in post-treatment group received a 5-day of lycopene following administration of cisplatin. Cisplatin (7 mg kg−1) was intraperitoneally (i.p.) injected as a single dose and lycopene (4 mg kg−1) was administered by gavage in corn oil. Traits of reproductive organs; sperm characteristics, testicular histological findings, plasma testosterone levels and the testicular tissue oxidative status were determined.

Administration of cisplatin to rats decreased sperm concentration (p < 0.05) and sperm motility (p < 0.001), increased total abnormal sperm rates (p < 0.05) as compared with the control group. While a marked normalization was achieved only in sperm concentration with lycopene in pre-treatment group, significant normalizations were achieved in the sperm concentration, sperm motility, total abnormal sperm rates in post-treatment group. No significant differences in levels of testosterone were observed among all groups. An increase in testes malondialdehyde concentrations (p < 0.05) and glutathione peroxidase activities (p < 0.001) were detected while significant decreases in glutathione levels (p < 0.001) in cisplatin alone group when compared to control group. While pre-treatment with lycopene restoring only malondialdehyde concentrations, its post-treatment caused normalization in both malondialdehyde and glutathione levels when compared with the cisplatin alone group. On the other hand, significant increases were determined in GSH-Px activities in all experimental groups when compared with the control group.

Although the mechansim is not clear, the results from this experimental study suggest that the lycopene have a possible protective effect against cisplatin-induced spermiotoxicity, effect of giving lycopene after cisplatin being superior to the giving it before cisplatin.

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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