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Protective effect of melatonin against zonisamide-induced reproductive disorders in male rats.

Khalil WK, Abdu F - Arch Med Sci (2013)

Bottom Line: The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats.Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats.The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS.

View Article: PubMed Central - PubMed

Affiliation: Cell Biology Department, National Research Centre, Dokki, Giza, Egypt.

ABSTRACT

Introduction: Zonisamide (ZNS) is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. The pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone (LH) surge. The aim of the present work was to study the protective effect of melatonin against the potential suppression impact of ZNS on reproductive activity.

Material and methods: Ninety adult albino male rats were allocated to several groups treated with melatonin (10 mg/kg BW), ZNS (10, 20 and 50 mg/kg BW) and 10 mg/kg of melatonin plus ZNS (10, 20 or 50 mg/kg BW, respectively). Reproductive hormones (testosterone, LH and follicle-stimulating hormone (FSH)) levels were measured in animal serum. Sperm abnormalities and DNA fragmentation in testis tissues as well as expression alteration of several reproductive-related genes were analyzed.

Results: The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats. In addition, ZNS treatment increased the sperm abnormalities and DNA fragmentation and inducible nitric oxide synthase (iNOS) in testis tissues as well as GABA level in liver tissues. However, melatonin supplementation inhibited the negative symptoms of ZNS in which it increased the levels of reproductive hormones and expression of their encoding genes in the ZNS-treated rats. Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats.

Conclusions: The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS.

No MeSH data available.


Related in: MedlinePlus

Relative expression of FSH gene in brain tissues of male rats after exposure to ZNS and/or melatonin. Mean values in the same column with different superscript letters differ significantly (p < 0.05)ZNS – Zonisamide, CP – cyclophosphamide.
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Figure 0006: Relative expression of FSH gene in brain tissues of male rats after exposure to ZNS and/or melatonin. Mean values in the same column with different superscript letters differ significantly (p < 0.05)ZNS – Zonisamide, CP – cyclophosphamide.

Mentions: The effect of melatonin and ZNS on the expression of CYP19 in the testis tissues and LH as well as FSH genes in pituitary tissues of adult male rats is summarized in (Figures 4–6).


Protective effect of melatonin against zonisamide-induced reproductive disorders in male rats.

Khalil WK, Abdu F - Arch Med Sci (2013)

Relative expression of FSH gene in brain tissues of male rats after exposure to ZNS and/or melatonin. Mean values in the same column with different superscript letters differ significantly (p < 0.05)ZNS – Zonisamide, CP – cyclophosphamide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495141&req=5

Figure 0006: Relative expression of FSH gene in brain tissues of male rats after exposure to ZNS and/or melatonin. Mean values in the same column with different superscript letters differ significantly (p < 0.05)ZNS – Zonisamide, CP – cyclophosphamide.
Mentions: The effect of melatonin and ZNS on the expression of CYP19 in the testis tissues and LH as well as FSH genes in pituitary tissues of adult male rats is summarized in (Figures 4–6).

Bottom Line: The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats.Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats.The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS.

View Article: PubMed Central - PubMed

Affiliation: Cell Biology Department, National Research Centre, Dokki, Giza, Egypt.

ABSTRACT

Introduction: Zonisamide (ZNS) is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. The pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone (LH) surge. The aim of the present work was to study the protective effect of melatonin against the potential suppression impact of ZNS on reproductive activity.

Material and methods: Ninety adult albino male rats were allocated to several groups treated with melatonin (10 mg/kg BW), ZNS (10, 20 and 50 mg/kg BW) and 10 mg/kg of melatonin plus ZNS (10, 20 or 50 mg/kg BW, respectively). Reproductive hormones (testosterone, LH and follicle-stimulating hormone (FSH)) levels were measured in animal serum. Sperm abnormalities and DNA fragmentation in testis tissues as well as expression alteration of several reproductive-related genes were analyzed.

Results: The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats. In addition, ZNS treatment increased the sperm abnormalities and DNA fragmentation and inducible nitric oxide synthase (iNOS) in testis tissues as well as GABA level in liver tissues. However, melatonin supplementation inhibited the negative symptoms of ZNS in which it increased the levels of reproductive hormones and expression of their encoding genes in the ZNS-treated rats. Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats.

Conclusions: The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS.

No MeSH data available.


Related in: MedlinePlus