Risperidone induced reproductive toxicity in male rats targeting leydig cells and hypothalamic–pituitary–gonadal axis by inducing oxidative stress

Abstract

Infertility affects 15% of couples worldwide as the disease of the reproductive system and 30%-50% of infertile cases are related to male-dependent factors (Ghuman & Ramalingam, 2017; 'Mother or nothing: the agony of infertility', 2010). Recent studies have shown that sperm quality is decreasing all over the world. The exact cause of this situation has not been fully understood; however, chronic exposures to chemicals especially drugs take an important place (Gabrielsen & Tanrikut, 2016). The complex aetiology underlying male-factor infertility makes it harder to understand at what level drug exposures are responsible for it. Additionally, the number of chronic disease cases, such as migraine, depression, and epilepsy, is increasing year by year, pointing out the fact that long-term drug exposures become frequently because of the need of treating these diseases at younger ages (Kristensen, 2018). Schizophrenia is a serious psychiatric disorder, results in longterm antipsychotic treatment. Today, atypical antipsychotics are the

The effect of Fumaria parviflora on the expression of sexual hormones along with their receptors in testicles of adult rats induced by varicocele

“…The precise mechanism underlying the pathogenesis of VCL has not yet been elucidated; however, several lines of evidence suggest that oxidative stress, endocrine disorders, and aberrant apoptosis are thought to be involved in this scenario (Chang et al, 2010). Oxidative stress affects the hypothalamus-pituitary-gonadal (HPG) axis in the male reproductive system and could disrupt its crosstalk with other hormonal axes (Görmüs ¸et al, 2021). Reactive oxygen species (ROS) can increase the level of cortisol through the HPA axis, which in turn reduces pituitary hormone secretion, including LH and FSH.…”

Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations

“…Furthermore, immune function pathways related to T cell maturation/differentiation were among the most heavily impacted by risperidone treatment, strongly suggesting that reduced plasma con- centrations of multiple cytokines and immune modulators is a mechanism for the risperidone induced immunosuppression [28,29]. Previous experimental evidences have established risperidone can damage to the different cells by inducing oxidative stress [10,11,24].…”

“…For evaluation of GSH, the supernatant was diluted with phosphate-EDTA buffer and incubated with 100 µl of the o-phthalaldehyde (OPT) solution for 15 min at room temperature. For determination of GSSG, the supernatant of the cells was diluted with NaOH 0.1 N solution and before incubation with OPT, 200 µl of Nethylmaleimide [24] solution was incubated with supernatant for 30 min. The fluorescence intensity was measured by UV spectrophotometer (Shimadzu RF5000U) at the excitation wavelength of 350 nm and the emission wavelength of 420 nm [25,26].…”

“…To achieve this aim, lymphocytes were isolated using Ficoll paque plus. The results showed that risperidone (12,24 and 48 nM) causes toxicity in human blood lymphocytes by increasing the level of intracellular reactive oxygen species (ROS), damage to lysosomal membrane, the collapse of the mitochondrial membrane potential (MMP), and increased extracellular oxidized glutathione (GSSG). Also, exposure of human blood lymphocytes to risperidone is associated with a decrease in intracellular glutathione (GSH) levels.…”

“…In addition, risperidone has the ability to decrease the level of intracellular antioxidant enzymes, including glutathione (GSH), and increase the level of lipid peroxidation (LPO). These events indicate oxidative stress [10][11][12]. Reports indicate that some antipsychotic drugs, such as risperidone, have the ability to inhibit and impair mitochondrial electron transport chain (mETC) function.…”