All treatments led to an equal increase in astrocyte ramification (Figures 4K and L). The ramification of the astrocytes from ORX rats decreased, as indicated by the decline in number of GFAP intersections and area under the curve of GFAP intersections. The complexity of astrocyte morphology was further investigated by Sholl analysis. The microglial ramification of ORX rats was decreased as indicated by the decline in number of Iba1 intersections and area under the curve of Iba1 intersections. The complexity of microglial morphology was further investigated by Sholl analysis.
N-acetylcysteine can be given orally, intravenously, topically, or through inhalation. NAC is commonly taken as a supplement for health and wellness and is used in clinical settings to treat drug overdose, cystic fibrosis, and chronic obstructive pulmonary disease. It has antioxidant, anti-inflammatory, and mucus thinning properties. N-acetylcysteine (NAC) is a precursor for the amino acid L-cysteine.
To investigate blood-brain-barrier permeabilization, the expression of hippocampal tight junction proteins including claudin-5 and occludin were measured by immunoblotting. Similar to insulin sensitivity, plasma triglyceride, plasma cholesterol, plasma HDL and LDL levels were not significant difference between ORX rats and sham-operated rats. ORX rats showed significantly decreased body weight, food intake, and visceral fat weight when compared to those of sham-operated rats (Table 1). NAC, and inulin attenuated gut dysbiosis, but the combined therapy and testosterone replacement had better efficacy to restore the balance of gut microbiota in the testosterone-deprived condition. These findings suggested that testosterone-deprived rats developed gut dysbiosis. Previous study reported that consumption of 10% inulin for 4 weeks markedly shifted the composition of gut microbiota and improved intestinal function . The diet of treated rats was prepared by adding 10% of inulin fiber into the control diet (by weight).
Most of such clinical studies have evaluated men with high levels of sperm DNA damage. The three-month supplementation with NAC significantly improved sperm parameters (count, motility and normal morphology) from pre-treatment baseline. Mean of TAC significantly increased after treatment with NAC compared to before treatment. Percentage of protamine deficiency in sperm significantly decreased after treatment with NAC compared to before treatment. Percentage of DNA fragmentation in sperm significantly decreased after treatment with NAC compared to before treatment. Data before and after NAC treatment were compared by the paired t-test via the statistical package for social studies (SPSS software, Version 20 Chicago, IL, USA).
NAC may be less toxic and more soluble than l-cysteine itself, which is why NAC is often used in supplements instead of l-cysteine by itself. So, increasing l-cysteine supply can increase this rate. Scientists believe that the supply of l-cysteine in the cell limits the rate of glutathione production in the body. The body then uses l-cysteine to make glutathione, which is a tripeptide or chain of amino acids composed of cysteine, glycine, and glutamic acid. In the body, NAC converts to l-cysteine, a nonessential amino acid.
Hormones are also metabolized and eliminated through these systems, emphasizing the important role of the liver in maintaining optimal hormone balance (19). Antioxidant defenses work in tandem with these pathways, neutralizing ROS, safeguarding the liver from oxidative stress, and maintaining overall cellular health. This delicate equilibrium is influenced by hormone production, transport, and metabolism. This study was approved by the ethics committee of the Azad Medical University. RJ, MN, KP and NH contributed in conception, design, statistical analysis and drafting the manuscript. The primary data for this study is available from the authors upon direct request.
A total of 50 infertile men with terato-asthenozoospermia and a mean age of 25–40 years were enrolled in the unit of ACECR Infertility Research Center, Qom, Iran, in 2018. This study was conducted as a randomized, blinded clinical trial. NAC also contributes to glutathione (GSH) synthesis and may help restore the depleted pool of GSH often caused by oxidative stress and inflammation 17, 18. Antioxidant capacity in the idiopathic infertile male population is lower than that of fertile men, who exhibit significantly greater seminal ROS production .
Based on the above, the present study was conducted to investigate the effects of daily oral NAC supplementation on the quality of semen parameters, chromatin integrity and reproductive hormones in asthenoteratozoospermic men. After NAC treatment, patients’ sperm count and motility increased significantly whereas abnormal morphology, DNA fragmentation and protamine deficiency showed significant decreases compared to pre-treatment levels (P P P The possible explanation is that the castrated condition and time course of castration in this study may induce only mild pathological condition in the brain, therefore the monotherapy by NAC and inulin can completely mitigate those deleterious effects. A previous study reported that 10% inulin improved cognitive performance in the light extinction test and the wellbeing of male rats using the functional observational battery assessment tool (FOB) . The underlying mechanisms of neuronal apoptosis in castrated rats may be due to increased oxidative stress and microglial hyperactivation, leading to releases several pro-inflammatory cytokines and brain inflammation . The present study and other also demonstrated an increase in hippocampal TUNEL positive cells of castrated male rats, resulting to cognitive decline. Moreover, our previous studies have shown that testosterone deprivation increased apoptosis, as measured by increasing levels of apoptotic proteins .
Taken together, our findings suggest that BBB dysfunction, brain oxidative stress, and brain inflammation develop as a result of testosterone deprivation, but these deleterious effects can be attenuated by testosterone replacement, NAC, inulin, and the combined therapy. In addition, a previous study in germ-free male mice demonstrated lower systemic testosterone levels compared with conventionally-raised counterparts . The effects of NAC, inulin and combined therapy on hippocampal plasticity in rats with testosterone deprivation.