The effects of carbamazepine on sperm morphology in wistar rats.

Carbamazepine (5 H-dibenz (b, f) azepine-5-carboxamide), is an antiepileptic drug which is expected to be administered regularly over a substantial part of patients lifetime. As the gender focus in epilepsy the later years has primarily been on women, there certainly is a lack of studies focused on the effects particular to men. The present study was aimed to investigate its effects on germ cell's by employing the sperm morphology assay. Twelve groups of male wistar rats were treated with sterile water 0.5 ml, cyclophosphamide (CP) 20 mg/kg, carbamazepine 9, 18, 36 mg/kg (i.p) and 2% gumacasia 0.25 ml/100 g respectively for 5 consecutive days at intervals of 24 hrs. Following the last exposure, on days 14 and 35 sperm morphology assay was conducted as per the standard procedure. Mann-Whitney 'U' test was used for statistical analysis and the level of significance was P<0.01. Neither carbamazepine nor cyclophosphamide induced formation of abnormally shaped sperms at 14 day time interval. Whereas on day 35, with 18 mg/kg dose level of carbamazepine there was an increase in the number of sperms with heads defects (P<0.01); Whereas in the other two dose levels the number of abnormally shaped sperms had decreased. 2% gumacasia increased the number of sperms with tail defects at day 35. (Mann-Whitney 'U' test). CONCLUSION: Carbamazepine and 2% gumacasia could be germ cell mutagens and could cause infertility on prolonged use therefore further studies with serum drug level estimations are needed.

Cyclic nucleotide phosphodiesterase inhibition increases tyrosine phosphorylation and hyper motility in normal and pathological human spermatozoa

Our objective was to determine the effect of phosphodiesterase (PDE) inhibition on: 1) tyrosine phosphorylation of human spermatozoa at the tail level; and 2) sperm motion parameters and hyperactivated motility. The study was conducted with normozoospermic and asthenozoospermic samples incubated under in vitro capacitating conditions. The main outcome measures were computer-assisted sperm motion analysis and fluorescent immunodetection of phosphotyrosine-containing proteins. Pentoxifylline (PTX) was used as PDE inhibitor because of its wide use in the clinic. PTX-treatment significantly increased sperm velocity, hyperactivated motility and tyrosine-phosphorylation, both in normo and asthenozoospermic samples. Tyrosine-phosphorylation of tail proteins was highly conspicuous in both types of samples, showing no differential pattern after PTX-treatment. Normozoospermic samples treated with pentoxifylline showed an increase in the number of spermatozoa displaying hyperactivated movement and tyrosine-phosphorylation at the tail level. Preliminary data on asthenozoospermic samples exhibiting altered motion characteristics and defective phosphorylation of sperm-tail proteins showed that both defects can be concomitantly overcome by pentoxifylline treatment. Tyrosine-phosphorylation of sperm-tail proteins is underlying the enhancement of hyperactivated motility resulting from PDE inhibition by pentoxifylline.