Limits...
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

DNA fragmentation detected with agarose gel of DNA extracted from testis tissues of rats exposed to ZNS and/or melatonin analyzed by DNA gel electrophoresis laddering assay. Lane 1 represents DNA ladder. Lane 2 represents control samples. Lane 3 shows DNA fragmentation in testis tissues following melatonin exposure. Lanes 4– 6 show DNA fragmentation in testis tissues following 10, 20 and 50 mg/kg of ZNS, respectively. Lanes 7–9 show DNA fragmentation in testis tissues following melatonin plus ZNS as in lanes 4–6. Lane 10 represents CP-treat ed samples
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4495141&req=5

Figure 0003: DNA fragmentation detected with agarose gel of DNA extracted from testis tissues of rats exposed to ZNS and/or melatonin analyzed by DNA gel electrophoresis laddering assay. Lane 1 represents DNA ladder. Lane 2 represents control samples. Lane 3 shows DNA fragmentation in testis tissues following melatonin exposure. Lanes 4– 6 show DNA fragmentation in testis tissues following 10, 20 and 50 mg/kg of ZNS, respectively. Lanes 7–9 show DNA fragmentation in testis tissues following melatonin plus ZNS as in lanes 4–6. Lane 10 represents CP-treat ed samples

Mentions: Quantitative DNA fragmentation was determined in rats exposed to ZNS alone or in combination with melatonin. The DNA damage was examined in testis tissues collected from ZNS-treated groups using gel electrophoresis laddering assay (Figure 3). The results of this assay revealed that ZNS treatment increased the DNA damage compared with the control group (Figure 3). DNA damage was observed with medium and high doses of ZNS. However, the low dose of ZNS did not induce damage in the DNA of the testis tissues of male rats.


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

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

DNA fragmentation detected with agarose gel of DNA extracted from testis tissues of rats exposed to ZNS and/or melatonin analyzed by DNA gel electrophoresis laddering assay. Lane 1 represents DNA ladder. Lane 2 represents control samples. Lane 3 shows DNA fragmentation in testis tissues following melatonin exposure. Lanes 4– 6 show DNA fragmentation in testis tissues following 10, 20 and 50 mg/kg of ZNS, respectively. Lanes 7–9 show DNA fragmentation in testis tissues following melatonin plus ZNS as in lanes 4–6. Lane 10 represents CP-treat ed samples
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 0003: DNA fragmentation detected with agarose gel of DNA extracted from testis tissues of rats exposed to ZNS and/or melatonin analyzed by DNA gel electrophoresis laddering assay. Lane 1 represents DNA ladder. Lane 2 represents control samples. Lane 3 shows DNA fragmentation in testis tissues following melatonin exposure. Lanes 4– 6 show DNA fragmentation in testis tissues following 10, 20 and 50 mg/kg of ZNS, respectively. Lanes 7–9 show DNA fragmentation in testis tissues following melatonin plus ZNS as in lanes 4–6. Lane 10 represents CP-treat ed samples
Mentions: Quantitative DNA fragmentation was determined in rats exposed to ZNS alone or in combination with melatonin. The DNA damage was examined in testis tissues collected from ZNS-treated groups using gel electrophoresis laddering assay (Figure 3). The results of this assay revealed that ZNS treatment increased the DNA damage compared with the control group (Figure 3). DNA damage was observed with medium and high doses of ZNS. However, the low dose of ZNS did not induce damage in the DNA of the testis tissues of male rats.

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