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Effects of combined treatment of α-tocopherol, l-ascorbic acid, selenium and zinc on bleomycin, etoposide and cisplatin-induced alterations in testosterone synthesis pathway in rats

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Abstract

Purpose

To investigate the effects of therapeutically relevant dose levels of bleomycin, etoposide and cisplatin (BEP) on testicular steroidogenic enzymes, and possible protective effects of an antioxidant cocktail (AC).

Methods

Adult Sprague–Dawley rats received BEP with or without the AC (α-tocopherol, l-ascorbic acid, selenium and zinc) for either (a) 4 days (short term; 1.5, 15 and 3 mg/kg), or (b) three cycles of 21 days each (0.75, 7.5 and 1.5 mg/kg), or (c) the three cycles with a 63-day recovery period. The expression of steroidogenic enzymes were measured in the testes by Western blotting and immunofluorescent labeling.

Results

The short-term BEP exposure resulted in a decrease in scavenger receptor class-B1 and an increase in luteinizing hormone receptor (LHR). The AC with or without BEP has increased the levels of LHR, 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD, but without significant changes in testosterone levels. The three cycles of BEP up-regulated the expression of steroidogenic acute regulatory protein (StAR) and down-regulated that of cholesterol side chain cleavage enzyme (P450scc), cytochrome p450 17A1 (Cyp17A1, recovered by the AC) and 17β-HSD, associated with significant reduction in testosterone levels. The three cycles with the recovery time led to decreases in LHR, StAR, P450scc and Cyp17A1 and increases in 3β-HSD and 17β-HSD. The AC did not enhance the recovery of the enzyme levels.

Conclusion

The three cycles of BEP treatment inhibit the testosterone synthesis pathway even after the recovery time. The AC recovers the effects of BEP chemotherapy on a few steroidogenic enzymes.

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Abbreviations

17β-HSD:

17-Beta-hydroxysteroid dehydrogenase

3β-HSD:

3-Beta-hydroxysteroid dehydrogenase

Cyp17A1:

Cytochrome p450 17A1

Cyp19A1:

Cytochrome P450 19A1

LHR:

Luteinizing hormone receptor

P450scc:

Cholesterol side chain cleavage enzyme

SRB1:

Scavenger receptor type B class 1

StAR:

Steroidogenic acute regulatory protein

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Acknowledgments

This research work was funded by Kuwait University Grant Number MA02/08 and General Facility grant number SRUL02/13. The author is grateful to Ms. S. Verghese, Ms. J. Prashanth and Dr. S. Jacob for the technical assistance, and the Animal Resources Center for maintaining the experimental animals.

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The author declares no conflict of interest.

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  1. Department of Anatomy, Faculty of Medicine, HSC, Kuwait University, PO Box 24923, 13110, Safat, Kuwait

    Narayana Kilarkaje

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Correspondence to Narayana Kilarkaje.

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Kilarkaje, N. Effects of combined treatment of α-tocopherol, l-ascorbic acid, selenium and zinc on bleomycin, etoposide and cisplatin-induced alterations in testosterone synthesis pathway in rats. Cancer Chemother Pharmacol 74, 1175–1189 (2014). https://doi.org/10.1007/s00280-014-2592-8

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  • DOI: https://doi.org/10.1007/s00280-014-2592-8

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