CREM, PRM I and II gene expression in Wistar rats testes treated with antipsychotic drugs: Chlorpromazine, Rauwolfia vomitoria and co-administration of reserpine, zinc and ascorbic acid

Abstract

Objective: The literature has shown that synthetic antipsychotic drugs induce reproductive toxicity, while psychiatric patients treated with traditionally used antipsychotic herbs (Rauwolfia vomitoria) showed no traces of reproductive toxicity. Thus, this study aimed to investigate the expression of CREM, PRM I and II genes in the testes of Wistar rats treated with antipsychotic drugs: chlorpromazine, Rauwolfia vomitoria (RV) and co-administration of reserpine, zinc and ascorbate (RAZ).

Methods: Forty-five adult male Wistar rats with rats with average weight of 180±4.67g were divided into nine groups (A-I) (n=5). Group A was administered saline (control) while rats in Groups B and C received 10 and 20mg/kg body weight (bwt) of chlorpromazine respectively. Groups D and E received 2.5 and 5mg/kg bwt of reserpine, respectively; while Groups F and G received 150 and 300mg/kg bwt of RV leaf extract. Groups H and I received (2.5+5+100) mg/kg bwt and (5+10+200) mg/kg of combination of RAZ, respectively for 56 days.

Results: The CREM, PRM I and II genes were significantly downregulated while significant decreased in serum FSH and testosterone concentration were found in the Chlorpromazine- and Reserpine-treated groups. Groups H and I showed a highly significant upregulation of the CREM, PRM I and II genes, and a highly significant increase in serum FSH and testosterone concentrations.

Conclusion: The study concluded that the HPT-Axis was impaired by chlorpromazine and reserpine, while RV and a combination of RAZ administration enhanced the axis in an animal model. The study recommended that synthetic antipsychotic drugs should be taken with Zinc and Ascorbate in order to help prevent reproductive toxicity associated with antipsychotic drugs. We need further studies in humans to confirm these findings.

Keywords: Rauwolfia vomitoria; antipsychotics; gene expression; testes.

Figure 1

Comparison in CREM gene expression among the groups after the administration of Chlorpromazine, Reserpine, Rauwolfia vomitoria and Co-administration of Reserpine, Ascorbate and Zinc. a=Comparison with Control Group A; b=Comparison with Group H and c=Comparison with group I. **p<0.01; ***p<0.001 (n=5).

Figure 2

Comparison of the PRM-1 gene expression among the groups after the administration of Chlorpromazine, Reserpine, Rauwolfia vomitoria and Co-administration of Reserpine, Ascorbate and Zinc. a=Comparison with Control Group A; b=Comparison with Group H and c=Comparison with group I.*p<0.05; **p<0.01; ***p<0.001 (n=5).

Figure 3

Showed comparison in PRM-2 gene expression among the groups after the administration of Chlorpromazine, Reserpine, Rauwolfia vomitoria and Co-administration of Reserpine, Ascorbate and Zinc. a=Comparison with Control Group A; b=Comparison with Group H and c=Comparison with group I.*p<0.05; **p<0.01; ***p<0.001 (n=5).

Figure 4

Showed comparison in Serum FSH Concentration among the groups after the administration of Chlorpromazine, Reserpine, Rauwolfia vomitoria and Co-administration of Reserpine, Ascorbate and Zinc. a=Comparison with Control Group A; b=Comparison with Group H and c=Comparison with group I.*p<0.05; **p<0.01; ***p<0.001 (n=5).

Figure 5

Comparison in Serum Testosterone Concentration among the groups after the administration of Chlorpromazine, Reserpine, Rauwolfia vomitoria and Co-administration of Reserpine, Ascorbate and Zinc. a=Comparison with Control Group A; b=Comparison with Group H and c=Comparison with group I.*p<0.05; **p<0.01; ***p<0.001 (n=5).

Figure 6

Comparison in Serum Prolactin Concentration among the groups after the administration of Chlorpromazine, Reserpine, Rauwolfia vomitoria and Co-administration of Reserpine, Ascorbate and Zinc. a=Comparison with Control Group A; b=Comparison with Group H and c=Comparison with group I.*p<0.05; **p<0.01; ***p<0.001 (n=5).