Testicular effects of monensin, a golgi interfering agent in male rats.

OBJECTIVE: The present study was undertaken to explore the effects of monensin, a potent Golgi disturbing agent on male fertility. METHODS: Male Wistar rats were administered monensin at the dose levels of 2.5, 5, and 10 mg/kg b wt. Animals were sacrificed after 67 days of the treatment. The activities of lactate dehydrogenase (LDH), ATPase, acid phosphatase and thiamine pyrophosphatase (TPPase) were measured in the testis. Cytochemical assay of Golgi body marker enzyme, thiamine pyrophosphatase was also performed. Ultrastructural changes in testis were studied by Transmission electron microscopy. Sperm number and motility were also examined. RESULTS AND DISCUSSION: The alterations in the activities of above mentioned enzymes indicate the pronounced effect of the drug on the functioning of spermatogenic cells. The findings from electron microscopy such as membrane disruption, swelling and disintegration of Golgi apparatus strongly suggest the interference of monensin with the functioning of Golgi apparatus in the spermatogenic cells. Data from the sperm number and motility as well as the fertility studies and the resulted litter size further points towards the antifertility effects of monensin in male rats. CONCLUSION: The findings from the present study strongly indicated the effects of monensin on the testis, involving alterations in key enzyme activities and changes at the ultrastructural level.

Effect of monensin, a Na+-specific carboxylic ionophore on the oxidative defense system in rat testis.

The effect of monensin, a Na+-specific ionophore on the oxidative defense system in rat testis was studied. Monensin mixed in the animal diet was administered at the dose levels of 2.5, 5 and 10 mg/kg b.w. to Wistar rats for a period of 67 days. A marked inhibition in the activities of different oxidative defense enzymes such as catalase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and glutathione reductase was noticed, which indicates the possible involvement of free radicals in the antispermatogenic effects of monensin in rat testis. This was further substantiated by a significant increase in the generation of lipid peroxides along with the depletion of reduced glutathione. The drug treatment resulted in a significant change in apoptotic cell death as seen by an elevated fragmentation in the testicular genomic DNA. Monensin treatment also resulted in marked degenerative changes in the histoarchitecture of testis, such as depletion of different germ cell populations, vacuole formation and disorganization of seminiferous tubules. The results are indicative of the potential antispermatogenic effects of monensin in the rat.

Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase and DNA integrity in rat testicular cells in vitro.

Monensin, a sodium specific ionophore was evaluated for its in vitro effects on rat testis by studying changes at biochemical parameters as well as at the DNA level. It was observed that monensin produced marked alterations in the activities of various enzymes associated with the testicular functions. The significant inhibition of different enzymes of oxidative defense system points toward the generation of reactive oxygen species (ROS) by monensin treatment. The significant depletion of reduced glutathione and elevation in the level of lipid peroxidation further support the above findings. The significant inhibition of the activities of lactate dehydrogenase and adenosine triphosphatase shows the interference of monensin with the normal energy supply in spermatogenesis. Moreover, the significant increase in the activities of acid phosphatase and thiamine pyrophosphatase demonstrates the interference of monensin with the Golgi-lysosomal complex of the rat testis. Induced DNA fragmentation indicates towards the impact of monensin on the DNA integrity and apoptosis. Further studies are needed to understand the important molecular mechanisms responsible for these effects.

Alterations in oxidative stress-related parameters in rat testis following monensin administration.

Monensin, a carboxylic ionophore, is well known for Na(+)/H(+) exchanger activity across biological membranes. It is also used in the poultry industry for its useful effects as a food additive. The present study has been designed to investigate the effects of monensin on some oxidative stress-related parameters in rat testis. Monensin was administered intratesticularly (5 mug/testis) to both testes by a single dose to Wistar rats for different time periods. After the completion of the respective treatments, various parameters reflecting the antioxidant defense system of the tissue were monitored and marked changes were found in the activities of various enzymes as well as in the levels of reduced glutathione and lipid peroxidation. After 1, 2, 3, and 4 days of monensin treatment, the activity of superoxide dismutase was found to be unaltered. However, after 2 days of monensin treatment, glutathione-S-transferase and catalase showed inhibition in their activities along with the depletion of glutathione (reduced) accompanied by a marked increase in lipid peroxidation. The increase in lipid peroxidation was noticeable even after 1 day of monensin administration. The inhibition in glutathione-S-transferase and glutathione peroxidase activities was also observed along with an increase in lipid peroxidation at the end of the 3-day posttreatment period, while, the 4-day posttreatment schedule caused an increase in the activity of glutathione reductase and glutathione peroxidase that was also accompanied by an inhibition of catalase. The findings of the present study are indicative of the potential of monensin in testicular tissue in contraceptive intervention.