Induction of apoptosis, oxidative stress, hormonal, and histological alterations in the reproductive system of thiamethoxam-exposed female rats

Abstract

The present study aimed to investigate the oral toxic effects of 1/10 LD50 and 1/5 LD50 of thiamethoxam (TMX), a neonicotinoid insecticide, on the reproductive system of female Wistar rats. Thirty female rats were divided into three groups and supplied orally with either; saline solution, 1/10 LD50 of TMX (156 mg/kg) or 1/5 LD50 of TMX (312 mg/kg). The daily administration was extended for 30 days. Investigating the parameters of oxidative stress, hormonal levels, histopathological alterations, and the apoptotic markers (P53, BAX, BCL-2, and caspase-3) was performed in the uterus and ovary of rats. Results showed significant changes in the body weight gain, and relative weight of the left and right ovaries and uterus. Moreover, luteinizing hormone (LH), estradiol (ED), and progesterone (PG) serum levels were not significantly altered following TMX oral administration. The level of follicle-stimulating hormone in the TMX-exposed group (156 mg/kg) was significantly increased; however, a significant decrease was observed in TMX-exposed animals (312 mg/kg). TMX induced significant oxidative stress in exposed groups by reducing the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), and elevating malondialdehyde (MDA) levels. Following hematoxylin and eosin staining, the microscopic examination revealed deteriorated luteal cells with vacuolation in the corpus luteum, a follicle containing a degenerated oocyte and degeneration/necrosis of the circular muscle layer with a high rate of apoptotic cells in TMX-exposed animals. TMX induced transcriptional alterations in apoptosis-related genes shifting towards the activation of the intrinsic apoptotic pathway. Collectively, results suggest the toxic effect of the TMX on the reproductive health of female Wistar rats.

The Effect of Acetamiprid Administration on Bcl-2 Immunoreactivity in the Liver

“…It was reported that thiamethoxam, one of the neonicotinoids, induced pathological lesions in the uterus and ovaries of rats and increased caspase-3 immunoreactivity in the uterus and ovaries compared to the control group. Furthermore, it was reported that Bcl-2 levels, one of the markers associated with apoptosis, were down-regulated, the Bax/bcl-2 ratio rose by up to 52% in contrast to the control group, and p53 expression was up-regulated (El-Din et al, 2023). A study by Nur et al in which they examined the immunoreactivity of Bcl-2 and p53 apoptotic markers showed an increased expression of p53-one of the cell death receptors parallel with the pathological changes in the kidneys resulting from acetamiprid-induced nephrotoxicity and a decrease in antiapoptotic Bcl-2 expression due to suppression (Nur et al, 2022).…”

The protective role of l-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats

“…With growing evidence of NEO neurotoxicity, there is an urgent need for a better understanding of their negative effects on nontarget organisms (Wang et al 2018 ; Habotta et al 2023 ). TMX is a potent NEO insecticide that has been shown to affect a variety of physiological indices and histological structures in albino rats (El-Din et al 2023 ). LC has already been shown to have a significant neuroprotective effect against aspartame (Hamza et al 2020 ), atrazine (Aziz et al 2018 ), bisphenol A (Edres et al 2018 ), and valproic acid (Nouri et al 2022 ; Salimi et al 2022 ) toxicity.…”

Impact of Perinatal Coexposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs

“…As a result, the delicate balance within the ovarian cells is disrupted. The apoptosis process is initiated as a protective response to eliminate cells that are severely affected by the ROS-induced damage [ 75 , 76 , 77 , 78 ].…”