Oral exposure to polystyrene nanoplastics altered the hypothalamic-pituitary-testicular axis role in hormonal regulation, inducing reproductive toxicity in albino rats.

BACKGROUND: Nanoplastics can be considered a novel contaminant for the environment because of their extensive applications in modern society, which represents a possible threat to humans. Nevertheless, the negative effect of polystyrene nanoplastics (PS-NPs) on male reproduction, fertility, and progeny outcomes is not well known. Thus, the aim of the present work was to calculate the median lethal dose (LD50) and investigate the consequences of exposure to PS-NPs (25 nm) on male reproductive toxicity. METHODS: This investigation first determined the LD50 of PS-NPs in male Wistar rats, and then in a formal study, 24 rats were distributed into three groups (n = 8): the control group; the low-dose group (3 mg/kg bw); and the high-dose group (10 mg/kg bw) of PS-NPs administered orally for 60 days. On the 50th day of administration, the fertility test was conducted. RESULTS: The LD50 was determined to be 2500 mg/kg. PS-NP administration induced significant alternations, mainly indicating mortality in the high-dose group, a significant elevation in body weight gain, declined sperm quality parameters, altered reproductive hormonal levels, thyroid endocrine disruption, an alternation of the normal histo-architecture and the histo-morphometric analysis of the testes, and impaired male fertility. CONCLUSION: Altogether, the current findings provide novel perspectives on PS-NP general toxicity with specific reference to male reproductive toxicity.

Biological impacts of the green synthesized silver nanoparticles on the pregnant albino rats and their fetuses.

BACKGROUND: With the increasing production and applications of silver nanoparticles (AgNPs), they can be released into the air, water, and soil environments leading to direct exposure to human beings. On this, the current study revealed the physiological, histological, and genotoxic effects of the green biosynthesized AgNPs using two methods; lemon juice or saponin reduction on the maternal and fetal tissues. METHODS: Twenty-eight pregnant female rats were divided into four groups (seven/group) and orally administrated the corresponding treatment doses once daily from the first to the 19th gestational day. The first group was administered distilled water as a control. The second group was administrated saponin. The third was administrated AgNps. The fourth was administrated saponin-loaded silver nanoparticles (Sn-AgNPs). RESULTS: Compared with the control group, the serum of pregnant rats treated with saponin, AgNPs, and Sn-AgNPs exhibited significant alterations in liver and kidney function parameters. In addition, maternal hepatic and renal tissues showed elevated oxidative stress, with a significant increase in the comet parameters. Histologically, both mothers and fetuses showed changes in the liver and kidney tissues. CONCLUSIONS: Green synthesized AgNPs have toxic effects on maternal and fetal tissues. Sn-AgNPs revealed an increase in the transfer, accumulation, and toxicity.

The impact of mesenchymal stem cells on doxorubicin-induced testicular toxicity and progeny outcome of male prepubertal rats.

BACKGROUND: Many therapies to treat cancer are gonadotoxic and can lead to infertility. New strategies to diminish the side effects and protective plans during and after chemotherapy are needed. Therefore, bone marrow mesenchymal stem cells (BM-MSCs) as a novel solution were investigated against doxorubicin (Dox)-induced toxicity in rat testes. METHODS: Forty male albino prepubertal rats were divided into four groups, 10 rats per each group. The first was injected intraperitoneally with saline as control. The second group was injected intravenously with a single dose of BM-MSCs (2 × 106 cells). The third was injected intraperitoneally with a single dose of Dox (5 mg/kg b.wt). The fourth was injected with both Dox and BM-MSCs as previously mentioned. Rats were cohabited each separately with an untreated adult female after 8 weeks of treatment to examine Dox effects on male's fertility. RESULTS: BM-MSCs counteract the deleterious effects of Dox on body, testicular weight as well as sperm quality by increasing sperm concentration and reducing the rate of abnormal sperm. BM-MSCs reduced significantly the testicular oxidative stress by reducing the elevated level of malondialdehyde and increasing the antioxidant capacity. Histologically, the testicular atrophy, severe damage of spermatogenesis and the significant reduction of the diameter and germinative cell layer thickness of the seminiferous tubules caused by Dox were significantly recovered after administration of the BM-MSCs. CONCLUSION: BM-MSCs have a significant role in restoring the structural efficiency of male reproductive system in rats after Dox treatment.

Melatonin improves the therapeutic role of mesenchymal stem cells in diabetic rats.

The present study aimed to investigate the role of bone marrow mesenchymal stem cells (MSCs) and/or melatonin (MT) for improvement of ß-cell functions in STZ diabetic rats. Male albino rats (130-150 g) were divided into six groups. CONTROL GROUP: received phosphate-buffered saline (PBS); melatonin group received melatonin (10 mg/kg b.wt./day for 2 months by oral gavage); diabetic untreated group; diabetic group treated with melatonin; diabetic group treated with MSCs (a single intravenous injection of 3 × 106 cell in PBS); and diabetic group co-treated with stem cells and melatonin. The results showed significant improvement in glucose, insulin, total antioxidant, and malondialdehyde level in diabetic rats treated with either MSCs alone or in combination with melatonin. The imumuno-histochemical analysis showed that MSCs and/or melatonin treatment reduced the rate of inflammation and apoptosis of the islet cells as well as increased the rate of pancreatic cell division. Such results were indicated by a significant improvement in the level of TNF-α, IL-10, PCNA, and caspase-3 to levels very close to the control. Co-treatment of MSCs and MT resulted in an improvement in the tissue of the pancreas and reduced number of damaged ß-cells. It can be concluded that co-treatment of stem cells and melatonin has a significant role in restoring the structural and functional efficiency of ß-cells in the pancreas more than stem cells alone. Such results may be due to the role of melatonin as an antioxidant in increasing the efficiency and vitality of stem cells.

Biomonitoring of the Genotoxic and Hepatotoxic Effects and Oxidative Stress Potentials of Itraconazole in Pregnant Rats.

BACKGROUND: Pregnant women are more susceptible to both vaginal colonization and infection by yeast. One hundred million fungal infected patients have been treated worldwide with itraconazole (Caputo, 2003. METHOD: Itraconazole was administrated orally to pregnant rats at doses of 75, 100, or 150 mg/kg during gestational days (GD) 1 to 7 or GD 8 to 14 or GD 14 to 20. The genotoxicity and hepatotoxicity of the antifungal drug itraconazole were assessed during different periods of pregnancy using different methods. RESULTS: It was found that itraconazole was a genotoxic drug for both mothers and fetuses. This finding was observed via significant elevation in the estimated comet assay parameters (percentage of fragmented DNA, tail moment, and olive moment), percentage of fragmented DNA measured by diphenylamine assay and mixed smearing and laddering of DNA fragments of liver samples. In addition, itraconazole caused significant elevation in the level of hepatic malondialdehyde and depletion in the catalase activity and glutathione level. Furthermore, itraconazole induced histopathological alterations in the hepatic tissues of both mothers and fetuses. CONCLUSION: These findings indicate that itraconazole administration at doses of 75, 100, or 150 mg/kg during pregnancy induced maternal and fetal toxicity that could be induced by the genotoxicity and the oxidative damage.

Fetotoxicity of 2,4-dichlorophenoxyacetic acid in rats and the protective role of vitamin E.

The present study was conducted to investigate the potential role of 2,4-dichlorophenoxyacetic acid (2,4-D) in inducing developmental toxicity and oxidative damage in pregnant rats and their fetuses as well as to assess the efficacy of vitamin E to prevent or alleviate such defects. Pregnant rats received 2,4-D (100 mg/kg bw) alone or in combination with vitamin E (100 mg/kg bw) daily from gestation day 1 to 19. The number of implantations, viable and resorbed fetuses and sex ratio were not statistically different among groups. However, fetuses maternally treated with 2,4-D were characterized by lower body weight and higher morphologic and skeletal defect rate. 2,4-D induced oxidative stress in the liver of mothers and fetuses which was indicated by a significant elevation of malondialdehyde level with reduction in catalase activity and total antioxidant capacity. Coadministration of vitamin E can counteract the deleterious effects of 2,4-D by successive reduction in the oxidative stress.

Impact of boric acid exposure at different concentrations on testicular DNA and male rats fertility.

The aim of this study was to investigate the consequences of exposure to three levels of boric acid (BA) on male rats reproduction, fertility and progeny outcome, with emphasis on testicular DNA level and quality. Adult male rats (12 weeks old) were treated orally with 125, 250 and 500 mg/kg bwt/d of BA for 60 d. The results indicated that BA administration at 125 mg/kg bwt had no adverse effects on fertility, sperm characteristics or prenatal development of the impregnated females. However, at dose 250 mg, BA treatment significantly increased serum nitric oxide, testosterone, estradiol levels and testicular boron and calcium levels and also significantly reduced serum arginase activity, sperm quality and testicular DNA content with minor DNA fragmentation. The impact of BA exposure at dose 250 mg on male rats fertility was translated into increases in pre-implantation loss with a resulting decrease in the number of live fetuses/litter. In addition to the significant alteration of biochemical measurements, observed at dose 250 mg, administration of BA at 500 mg caused testicular atrophy, severe damage of spermatogenesis, spermiation failure and significant reduction of Mg and Zn testicular levels. None of the male rats, treated with 500 mg/kg bwt, could impregnate untreated females, suggesting the occurrence of definitive loss of fertility. In conclusion, BA impaired fertility, in a dose-dependant manner, by targeting the highly proliferative cells, the germ cells, through decreasing DNA synthetic rate rather than the induction of DNA damage.