Pregabalin administration and withdrawal affect testicular structure and functions in rats

Abstract

The aim of this prospective experimental study was to investigate the effects of pregabalin (PG) administration and withdrawal on testicular structures and functions in rats. A total of 24 male Wistar rats were divided into two groups (n = 12 each): a control group received normal saline, and PG‐treated group received 62 mg kg‐1 day‐1 PG for 2 months. Half the animals of each group were sacrificed for the collection of blood and testicular samples. The remaining animals were bred for another 2 months without treatment before collection of blood and testicular samples. PG administration decreased testosterone and increased luteinising hormone (LH) and follicle‐stimulating hormone (FSH) levels versus controls. PG withdrawal led to a decrease in both FSH and LH and an increase in testosterone levels versus saline withdrawal. Compared to controls, PG administration caused degeneration of seminiferous tubules and decreased the number of spermatogenic but increased the number of Leydig cells. After PG withdrawal, these cells showed a rebound reverse. Reduced glutathione levels increased with PG administration while PG withdrawal increased malondialdehyde levels. Conclusion: PG administration affected testicular morphometry, gonadotrophic and sex hormones; however, there was a rebound reversal in all these parameters and a significant oxidative stress in PG withdrawal.

Effects of clinical medications on male fertility and prospects for stem cell therapy

“…Studies have shown that valproic acid can induce tissue pathological damage associated with autophagy by modulating the AMPK/mTOR signaling pathway ( Alsemeh et al, 2022 ). And another type of AEDs Pregabalin can reduce the number of germ cells while increasing the number of interstitial cells, and cause a decrease in the number and diameter of convoluted tubules ( Salem et al, 2020 ). It also induces cell apoptosis, increases caspase-3 expression in the testis ( Shokry et al, 2020 ), upregulates pro-apoptotic genes BAX and p38 MAPK, and downregulates the anti-apoptotic gene BCL2 ( Taha et al, 2020 ).…”