Reproductive troubles induced by ivermectin or triclabendazole and their combinations in male rats

The present study was carried out to evaluate the effect of administration of ivermectin and / or its interaction with triclabendazole on some reproductive organs weight, epididymal sperm characters and serum testosterone level in mature male rats. Sixty mature male rats were divided equally into 4 groups each of 15 rats. The first group received s.c. ivermectin [0.56 mg/kg. b.wt.], the second group received orally triclabendazole [35mg/kg b.wt.], the third group received ivermectin plus triclabendazole as previously mentioned and the fourth group received saline [control group]. After 31 days from drugs administration, the drugs were repeated to all groups. The obtained results showed that administration of two doses of ivermectin, triclabendazole or both together induced a variety of adverse effects. These are represented by certain fertility troubles as reduction of some reproductive organs weight, changes in semen characters [decrease of sperm count and motility and increase of total sperm abnormalities, as well as a decrease in serum testosterone level. It could be concluded that the most harmful effect on male fertility induced by a coadministration of ivermectin and triclabendazole than giving each drug alone

Synthesis and primary cytotoxic screening of some 3-sulfonamide substituted benzamido-benzimidazolones

Several cycline dependent kinase 2 [CDK2] inhibitors with different chemical structures have been introduced. The hinge region of CDK2 [residues 81_84] contains a set of hydrogen bond donor and acceptor sites some of which must be satisfied for potent inhibitor binding. The benzimidazolone skeleton may provide such interactions. Accordingly, 3-sulfonamide substituted benzamido-benzimidazolones 24-31 were prepared starting from benzoic acid to give the acyl chloride 1 which was reacted with different amines to afford the acids 2-9. The acids were changed to their corresponding acyl chlorides 10-17. Reaction of 10-17 with o-nitropheyl hydrazine gave the nitro derivatives 18-25 followed by reduction of the nitro groups to give 26-33 which were then reacted with ethyl chloroformate to give the target compounds 34-41. The 3-pyridyl derivative 47 was prepared starting with chlorosulfonyl benzoyl chloride to give the acid 43 which was changed to the corresponding acyl, nitro and amino derivatives 44, 45 and 46, respectively, followed by the final ring closure reaction to give 47. The dibenzimidazolinoe derivative 49 was also obtained from the reaction of isopropenyl-benzimidazolone 48 and 3-chloro sulfonyl benzoyl chloride. The target compounds were then tested against the cancer cell lines, Hepa G2, HT-29, CL1-5 and AGS. Results indicated that the target compounds did not show reasonable cell growth inhibition comparing to the positive and negative controls

Spermatotoxic effect of carbendazim.

Carbendazim, suspended in sunflower oil, was administered to Wistar male rats through an oral intubation at a daily dose of 25 mg/kg body weight for 48 days, and the cauda epididymal sperm were analysed on day 49 for counts, motility and abnormalities. The study indicates that carbendazim affects the cauda epididymal sperm as seen in decreased sperm counts, inhibition of motility and increased incidence of abnormalities.

Carbendazim generates symplasts in rat spermatogenic clones.

In order to find non-microtubular targets in the seminiferous epithelium for the fungicide and reproductive toxicant carbendazim, it was administered to 90 days old male Wistar rat in a single bolus dose of 400 mg/kg body weight through an oral intubation. A parallel control group was maintained. Rats were sacrificed 48 days after the treatment and the testes were analysed for histopathological changes adopting routine histological methods, when symplasts were localised. The maximum diameter of five largest symplasts was measured, and the number of nuclei in these symplasts was also determined. As it is known that symplasts of spermatogenic cells are produced due to opening up of the intercellular bridges between cells in a clone consequent upon disruption of actin microfilaments, the present study shows that actin microfilaments would also be targets in the seminiferous epithelium for carbendazim toxicity.