Most of the clinically infertile patients show spermatogenesis dysfunction. Cyclophosphamide, as an anticancer drug, can induce spermatogenesis dysfunction. Sesamin is the main bioactive component of natural lignans in sesame. It is abundant in sesame oil and has strong biological activities such as antioxidant, antibacterial, and hypoglycemic properties. By establishing the model of spermatogenic dysfunction induced by cyclophosphamide in male mice and then feeding sesamin (50, 100, and 200 mg/kg) for 2 weeks, we proved that sesamin can improve the reproductive organ damage induced by cyclophosphamide and increase the number and activity of sperms. Sesamin can resist cyclophosphamide-induced sperm nuclear maturity and DNA damage by increasing the expression levels of histones H2A and H2B in the testis. In addition, sesamin can improve the ubiquitination of histones regulated by RNF8 to protect the testis. In conclusion, these results suggest that sesamin can improve spermatogenic dysfunction induced by cyclophosphamide, which may be mediated by ubiquitination of histones.
Antiepileptic drugs have been shown
to be associated with inducing
or exacerbating adverse psychotropic reaction, including aggressive
behavior. Perampanel, the first pharmacological compound approved
by the FDA in 2012, is an effective antiepileptic drug for intractable
epilepsy but induces severe aggression. So far, the underlying molecular
mechanisms of aggression induced by perampanel remain incompletely
understood. In the present study, a model of aggressive behavior based
on the clinical use of perampanel was established and resident–intruder
test and open field test were performed. Changes in hippocampal protein
profiles were detected by tandem mass tag (TMT) proteomics. The behavioral
results indicated that long-term use of perampanel increased the aggressive
behavior of C57BL/6J mice. Proteomic analysis revealed that 93 proteins
were significantly altered in the hippocampus of the perampanel-treated
group (corrected
p
< 0.05), which were divided
into multiple functional groups, mainly related to synaptic function,
synaptogenesis, postsynaptic density protein, neurite outgrowth, AMPA-type
glutamate receptor immobilization, and others. Bioinformatic analysis
showed that differentially expressed proteins were involved in synaptic
plasticity and the Ras signaling pathway. Furthermore, validation
results by western blot demonstrated that glutamate receptor 1 (GluA1)
and phosphorylation of mitogen-activated protein kinase (ERK1/2) were
notably up-regulated, and synaptophysin (
Syn
) and
postsynaptic density 95 (PSD95) were down-regulated in perampanel-treated
mice. Therefore, our results provide valuable insight into the molecular
mechanisms of aggressive behavior induced by perampanel, as well as
potential options for safety treatment of perampanel in the future.
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