Effect of antiepileptic drug (Topiramate) and cold pressed ginger oil on testicular genes expression, sexual hormones and histopathological alterations in mice

Biomed Pharmacother. 2019 Feb:110:409-419. doi: 10.1016/j.biopha.2018.11.146. Epub 2018 Dec 5.


Sexual dysfunction in the epileptic patient is difficult to confirm whether it is ailment or therapy related. Antiepileptic drugs often use in reproductive age, through reproductive progress and maturation. On the other side, cold-pressed oils are rich in bioactive phytochemicals with health-promoting traits. The target of this work was to appraise the sexual dysfunction of antiepileptic Topiramate (TPM) and cold pressed ginger oil (CPGO) as antiepileptic alternative medicine in male mice. Fifty-four adult male albino mice were divided into nine groups (n = 6 mice). One group given saline and used as negative control; another one was given corn oil as vehicle. Six groups administered orally with TPM or CPGO at 100, 200 and 400 mg/kg. Moreover, group of animals co-administrated orally CPGO with TPM (400 mg/kg) to study their interaction. Fatty acid profile and tocols composition of CPGO were determined. in vitro assays were undertaken to evaluate radical scavenging traits of CPGO utilizing sable 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and galvinoxyl radicals. The study investigated antioxidant and oxidative stress markers, sexual hormones levels, mRNA levels of vascular endothelial growth factor (Vegfa), synaptonemal complex protein (Sycp3), Wilms tumor gene (Wt1) as well as histopathological and immunohistochemical examination. Strong radical scavenging potential of CPGO against stable DPPH· and galvinoxyl radicals was recorded. The results revealed that TPM caused a dose-dependent reduction in the antioxidant activities and testosterone content, while, malonaldehyde (MDA) and nitric oxide (NO) as oxidative stress markers were elevated. Vegfa and Sycp3 mRNA expression down-regulated at all Topiramate tested doses, but Wt1 up-regulated at 400 mg/kg. TPM (400 mg/kg) revealed histological alterations associated with strong positive Bax immune reactive spermatogoneal and Leydig cells. Ginger oil elevated the CAT and SOD (antioxidant enzymes), serum testosterone and diminished the oxidative stress, up regulated the expression of Vegfa and Sycp3 and down-regulated the Wt1 expression. Meanwhile, CPGO revealed no histopathological alterations and no Bax immune-reactive cells. CPGO co-administration with TPM (400 mg/kg) attenuated the TPM toxicity. High doses of TPM may exhibit sexual dysfunction but CPGO is safe and has androgenic property. CPGO co-administration could protect the antiepileptic patient from the TPM sexual dysfunction.

Keywords: Antiepileptic; Antioxidants; Cold pressed oils; Histopathology; Immunohistochemistry.

MeSH terms

  • Animals
  • Anticonvulsants / toxicity*
  • Gene Expression
  • Ginger*
  • Gonadal Steroid Hormones / biosynthesis*
  • Gonadal Steroid Hormones / genetics
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Plant Oils / administration & dosage*
  • Plant Oils / isolation & purification
  • Testis / drug effects
  • Testis / metabolism*
  • Testis / pathology
  • Topiramate / toxicity*


  • Anticonvulsants
  • Gonadal Steroid Hormones
  • Plant Oils
  • Topiramate