Corn Oil Control Research Articles

Ascorbic acid alleviates reproductive toxicity of di-(2-ethyl hexyl) phthalate in female Wistar rats

Objective: To investigate the potential of ascorbic acid in mitigating reproductive toxicity induced by di-(2-ethyl hexyl) phthalate (DEHP) in female Wistar rats, focusing on oxidative stress, hormone levels, and gonadotropin receptors expression. Methods: Forty female Wistar rats [30 days old, weighing (60±10)g] were randomly divided into five groups (n=8 per group). Group 1 received corn oil (control). Groups 2 and 3 were administered DEHP at 10 and 100 mg/kg body weight (b.wt.), respectively. Groups 4 and 5 received DEHP at 10 and 100 mg/ kg b.wt., respectively, plus ascorbic acid 100 mg/kg b.wt.. All treatments were given orally for 30 days. Blood and ovarian tissues were collected to assess serum reproductive hormones, gonadotropin receptor gene expression, oxidative stress markers, and apoptosis. Results: DEHP, particularly at the higher dose, significantly decreased hormone levels (follicle-stimulating hormone, luteinizing hormone, estradiol) and gonadotropin receptor gene expression (FSHR, LHR), while increasing oxidative stress and apoptosis. Co-treatment with ascorbic acid significantly improved these parameters, reducing oxidative stress and apoptosis, and restoring hormone levels and gonadotropin receptor expression. Histopathology revealed fewer atretic follicles and less disruption in ovarian structure in DEHP and ascorbic acid-treated groups compared to those treated with DEHP alone. Conclusions: Ascorbic acid demonstrates protective effects against DEHP-induced reproductive toxicity in female rats, likely through mitigating oxidative stress and normalizing hormone levels and ovarian function.

Improvement in Glycolipid Metabolism Parameters After Supplementing Fish Oil-Derived Omega-3 Fatty Acids Is Associated with Gut Microbiota and Lipid Metabolites in Type 2 Diabetes Mellitus.

This study aimed to investigate the effects of fish oil-derived omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on gut microbiota and serum lipid metabolites in T2DM. In a three-month, randomized, double-blind, placebo-controlled study, 110 T2DM patients received either fish oil (n = 55) or corn oil (n = 55) capsules daily. Serum lipids, glycemic parameters, gut microbiota diversity, and lipidomics were assessed. This study found that fish oil-derived omega-3 PUFAs intervention did not significantly lower the fasting plasma glucose levels when compared with the baseline level (p > 0.05). However, serum fasting blood glucose (p = 0.039), glycosylated hemoglobin levels (p = 0.048), HOMA-IR (p = 0.022), total cholesterol (p < 0.001), triglyceride (p = 0.034), LDL cholesterol (p = 0.048), and non-HDL levels (p = 0.046) were significantly lower in the fish oil group compared with the corn oil group after three months of intervention. Also, it altered glycerophospholipid metabolism and gut microbiota. After three months, the fish oil group showed a significantly lower abundance of Desulfobacterota compared with the corn oil control group (p = 0.003), with reduced levels of Colidextribacter (p = 0.002), Ralstonia (p = 0.021), and Klebsiella (p = 0.013). Conversely, the abundance of Limosilactobacillus (p = 0.017), Lactobacillus (p = 0.011), and Haemophilus (p = 0.018) increased significantly. In addition, relevant glycolipid metabolism indicators showed significant correlations with the altered profiles of serum lipid metabolites, intestinal bacteria, and fungi. This study highlights the impact of fish oil-derived omega-3 PUFAs on intestinal microbiota structure and function in patients with type 2 diabetes. The observed decrease in pathogenic bacterial species and the enhancement of beneficial species may have significant implications for gut health and systemic inflammation, both of which are pivotal in managing diabetes. Further research is warranted to comprehensively elucidate the long-term benefits and underlying mechanisms of these microbiota alterations.

Administration of melatonin nanoparticles improves testicular blood flow, echotexture of testicular parenchyma, scrotal circumference, and levels of estradiol and nitric oxide in prepubertal ossimi rams under summer heat stress.

Environmental heat stress (HS) impairs reproductive efficiency in farm animals. This study investigated, for the first time, how the melatonin and melatonin nanoparticles treatment affected the testicular hemodynamics, testicular volume, echotexture [Pixel intensity (PIX) and integrated density (IND)], scrotal circumference, serum concentration of testosterone (T), estradiol (E2), nitric oxide (NO), and total antioxidant capacity (TAC) in prepubertal Ossimi ram lambs in hot climatic conditions. The lambs undergoing examination had a temperature humidity index (THI) of 87.05 ± 1.70, indicating severe HS condition. Fifteen prepubertal Ossimi ram lambs were exposed to a single s.c injection of either nano melatonin (nano melatonin group; 20mg/ram; n = 5) or melatonin suspended in two ml of corn oil (melatonin group; 40mg/ram; n = 5) or two ml of corn oil (control group; n = 5). Blood collection and ultrasonographic assessment of the testes and supratesticular arteries (STAs) were conducted immediately before treatment (W0) and once weekly for six successive weeks after nano melatonin and melatonin injection (W1-W6). Results revealed decreases (P < 0.05) in the Doppler indices (resistive index; RI and pulsatility index; PI) of the testicular arteries at most time points of the study in the nano melatonin and melatonin groups. PIX of testicular parenchyma was significantly increased (P ˂ 0.05) in the treated groups compared to the control one. IND of testicular parenchyma increased significantly in the nano melatonin group compared to the melatonin and control groups. Testicular volume and scrotal circumference significantly increased (P < 0.05) in nano melatonin and melatonin groups compared to the control one. T concentration did not significantly (P > 0.05) change in the treated groups compared to the control group. E2, NO, and TAC concentrations increased (P < 0.05) in the treated groups compared to the control one. In conclusion, this study extrapolated that administrations of melatonin or nano melatonin can ameliorate the effects of environmental HS in prepubertal Ossimi ram lambs with a more protective effect and lower dose of nano melatonin.

Se-Methylselenocysteine Ameliorates DEHP-Induced Ferroptosis in Testicular Sertoli Cells via the Nrf2/GPX4 Axis.

Di (2-ethylhexyl) phthalate (DEHP) is an important plasticizer in industrial production, and its toxic effects on testes are widely recognized. Se-methylselenocysteine (SMC) is a major selenium compound found in selenium-rich plants, which possesses unique biological properties such as antioxidants. However, the effect of SMC on DEHP-induced testicular injury and the specific mechanism remains unknown. In this study, 50 mice were randomly divided into 5 groups and were given corn oil (Control), DEHP, low-dose SMC (L-SMC), moderate-dose SMC (M-SMC), or high-dose SMC (H-SMC). The sperm quality of the mice in each group was determined, and HE staining and transmission electron microscopy (TEM) were applied to observe testicular morphology, and testicular tissues were collected for the subsequent molecular biological analyses. The TM4 cell line was applied in vitro for mechanism validation. Our results showed that DEHP could lead to decreased sperm quality and blood-testis barrier damage in mice, which could be alleviated by SMC. Mitochondrial damage accompanied by accumulation of total iron content, MDA, and 4-HNE, as well as downregulation of antioxidants SOD, GSH, and GSH-Px were observed after DEHP treatment, which exhibited a typical ferroptosis feature. In vitro experiments confirmed that SMC promoted upregulation of GPX4 in TM4 cells and was able to alleviate DEHP metabolite MEHP-induced ferroptosis and promote the expression of cell junction key proteins ZO-1, Occludin, and Connexin 43, which could be inhibited by the GPX4 inhibitor RSL3 or the Nrf2 inhibitor ML385. Overall, the above results suggest that SMC ameliorates the DEHP-induced ferroptosis in testicular Sertoli cells, protects the blood-testis barrier, and prevents sperm aberrations via the Nrf2/GPX4 axis.

Impacts of olfactory cues on equine feeding behavior

Anise has demonstrated equine palatability but its olfactory effect is underexplored. The objective was to investigate the effect of the aroma of anise on consumptive behavior. Stock-type horses (n = 8) were used in a crossover 6-day preference test. Palatability stocks were utilized. Bowls containing oats were situated on plates holding gauze soaked with 0.375 ml of anise or corn oil (control). Variables included first diet sniffed (FS), first consumed (FC), first action (FA), and amount consumed (AC). Each trial was video-recorded. Behavior data were analyzed using chi square and Kruskal-Wallis tests. FS and FC were elevated for anise treatment (P = 0.02; P = 0.04). For FA, sniffing was more frequent versus consuming (P < 0.01). AC for anise was twice the daily average of control (P < 0.01). Data represents an important relationship between olfactory stimuli and feeding in horses. To determine thresholds, more work is needed.

Neonatal vitamin A supplementation improves sheep fertility potential.

This study aimed to explore the effects of neonatal vitamin A (VA) supplementation on testis development and spermatogenesis. A total of 32 newborn lambs were intramuscularly injected with corn oil (control group) or corn oil + 2500 IU/kg BW VA (VA group). They were slaughtered and sampled at 3 weeks and 8 months of age to analyze spermatogenesis, cell proliferation, hormone secretion, antioxidant status of the testis, and adult sheep sperm parameters. Compared with the control group, the expression of spermatogonial differentiation-related genes in VA group was up-regulated (P < 0.05). Testis weight, seminiferous tubule diameter, number of spermatogonium and spermatocyte, and sperm density increased significantly in VA group at 8 months of age (P < 0.05). Neonatal VA injection upregulated the expression of the cell proliferation marker PCNA and cell cycle-related genes in the testis (P < 0.05). VA increased the concentrations of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the serum and upregulated steroidogenesis-related genes in the testis (P < 0.05). The antioxidant levels in the VA group were maintained at high levels. The total antioxidant capacity (T-AOC), antioxidant enzyme content and antioxidant-related genes were increased in the testis (P < 0.05). Furthermore, neonatal VA injection activated retinoic acid (RA) signaling to maintain the blood-testosterone barrier (BTB) in the testis of 3-week-old sheep. AMP-activated protein kinase (AMPK) and protein kinase B (AKT) signaling were also modulated in the sheep testis (P < 0.05). Taken together, VA supplementation in newborn rams promotes testis development and spermatogenesis to improve fertility.

Effect of Anise Seeds (Pimpinella anisum) Oil Extract on Some Fertility Parameters in Albino Male Mice

Anise is an aromatic plant which is used in traditional medicine and pharmaceutical industry. The main components of anise seed are anise alcohol, p-anisaldehyde, estragol, acetophenone, limonene and pinene, while the volatile oil found in anise is anethole. The antioxidant, antimicrobial, anticonvulsant and analgesic properties of anise seeds and oil have been confirmed by various studies. The current study was designed to study the effects of oral administration of anise oil on the reproductive capacity of adult male mice by examining certain physiological parameters such as measuring the serum testosterone level, counting the number of sperm, sperm motility and abnormal sperm morphology. A total of 36 male mice were used and randomly divided into three equal groups. Group1 received corn oil (control), T1 received anise oil in a dose of 0.043 gm/kg B.wt , and T2 received anise oil in a dose of 0.086 gm/kg B.Wt orally. The above mentioned parameters were examined at the end of three weeks of administration for six animals of each group. As well as, the examinations were repeated at the end of six weeks of administration for the rest of the animals. The results exhibited that treatment with anise oil led to a significant increase in the level of testosterone, sperm count and motility. Furthermore, abnormal morphology of the sperms decreased significantly. In conclusion, it can be said that the administered doses of anise oil could have led to improve the fertility in male mice.

Inulin alleviates perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure-induced intestinal toxicity by reshaping the gut microbiota and suppressing the enteric-origin LPS/TLR4/NF-κb pathway in dams and pups

Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.

Abstract 18: Toll-Like Receptor 4 Knockout Attenuates Microglia-Mediated Oxidative Stress and White Matter Toxicity

Background: Exposure to ambient air pollution causes neuroinflammation and white matter (WM) damage. In patients with preexisting cerebrovascular disease, pollution exposure can compound underlying pathology and may accelerate functional decline. Major mechanisms of this toxicity are microglial reactivity and oxidative stress. We therefore hypothesized that attenuation of the Toll-like receptor 4 (TLR4)-dependent microglial response would significantly decrease oxidative WM damage in a joint experimental model of pollutant exposure and chronic cerebral hypoperfusion modeled by surgical bilateral carotid artery stenosis (BCAS). Methods: Inducible microglial/macrophage-specific TLR4 deletion was achieved using a Tamoxifen-induced Cx3cr1CreER+/- mouse model. Male and female Cx3cr1CreER+/- mice treated with tamoxifen (i-mTLR4-ko) or corn oil (control) were exposed to 120 hours of filtered air (FA) or aerosolized diesel exhaust particulate (DEP), and 30 days of BCAS or sham surgery using a factorial design. The 8 experimental groups were: 1) control/FA (n=10), 2) control/DEP (n=10), 3) control/FA + BCAS (n=9), 4) control/DEP+BCAS (n=10), 5) i-mTLR4-ko/FA (n=9), 6) i-mTLR4-ko/DEP (n=8), 7) i-mTLR4-ko/FA + BCAS (n=8), and 8) i-mTLR4-ko/DEP+BCAS (n=10). Immunofluorescence was used to identify 4-HNE and 8-OHdG expression in the corpus callosum (CC). Results: While control mice showed elevations of 4-HNE in the CC after DEP (p&lt;0.01) and DEP+BCAS (p&lt;0.0001), i-mTLR4-ko prevented this change (Figure 1). While control mice exhibited a rise in 8-OHdG in the CC after DEP+BCAS (p&lt;0.05), i-mTLR4-ko prevented this rise. Conclusions: We demonstrate that i-mTLR4-ko is sufficient to abate major elevations in oxidative stress markers in WM after DEP and BCAS exposures. This suggests a potential role for therapies targeting TLR4 signaling to minimize pollution-associated neurotoxicity, particularly in the setting of cerebral hypoperfusion.

Abstract 019: Perimenopause Exacerbates Hypertension In Doca-salt Rats

Blood pressure (BP) is lower in premenopausal women than in age-matched men, but after menopause BP rates and the incidence of hypertension (HTN) show opposite tendencies. The mechanisms by which fluctuating ovarian hormone environment during that period impacts the onset and development of HTN are poorly understood, and strategies to reduce HTN risk in peri- and postmenopausal females are lacking. An ovary-intact rat model of perimenopause using the chemical, 4-vinylcyclohexene diepoxide (VCD), has been developed to accelerate the natural process of slow follicular loss. Daily dosing with VCD for 15 days selectively destroys primordial and primary follicles in ovaries of mice and rats by accelerating atresia processes, thus inducing precocious perimenopause/menopause. Hypothesis: The induction of perimenopause by VCD will increase susceptibility to the development of HTN in DOCA-salt rats. Female Sprague-Dawley rats at post-natal day 28 received subcutaneous injection of VCD (160mg/kg) or corn oil (control) for 15 days. 57 days after the first injections, nephrectomy and telemetric pressure transducer implantation were performed. After 2 weeks of recovery, a 100 mg/kg DOCA silicone or placebo pellet was implanted subcutaneously. The rats that received DOCA were provided 0.9% saline during the 21 days of DOCA protocol and mean arterial pressure (MAP) was continuously evaluated. Rats were housed weekly in metabolic cages for 24 hours to measure saline intake and urine volume. After protocol completion the animals were decapitated, and blood was collected for the measurement of anti-Mullerian hormone (AMH) and estradiol (E2) by ELISA. The AMH plasma levels were reduced in the periestropause rats (VCD + DOCA, n=9) compared to oil (Oil + DOCA, n=6) confirming the VCD-induced follicular depletion. The steady state increase in MAP (day 21 of DOCA-salt) was higher in periestropause (±45.7mmHg) compared to oil (±28.6 mmHg). Urine volume was higher in periestropause rats compared to oil. No differences were observed in the saline intake between the groups. Our data demonstrate that periestropause rats showed greater susceptibility to the development of HTN in a DOCA-salt rat model.

Vitamin A injection at birth improves muscle growth in lambs.

Vitamin A and its metabolite, retinoic acid (RA) play important roles in regulating skeletal muscle development. This study was conducted to investigate the effects of early intramuscular vitamin A injection on the muscle growth of lambs. A total of 16 newborn lambs were given weekly intramuscular injections of corn oil (control group, n=8) or 7,500 IU vitamin A palmitate (vitamin A group, n=8) from birth to 3wk of age (4 shots in total). At 3wk of age and weaning, biceps femoris muscle samples were taken to analyze the effects of vitamin A on the myogenic capacity of skeletal muscle cells. All lambs were slaughtered at 8 months of age. The results suggest that vitamin A treatment accelerated the growth rate of lambs and increased the loin eye area (P<0.05). Consistently, vitamin A increased the diameter of myofibers in longissimus thoracis muscle (P<0.01) and increased the final body weight of lambs (P<0.05). Vitamin A injection did not change the protein kinase B/mammalian target of rapamycin and myostatin signaling (P>0.05). Moreover, vitamin A upregulated the expression of PAX7 (P<0.05) and the myogenic marker genes including MYOD and MYOG (P<0.01). The skeletal muscle-derived mononuclear cells from vitamin A-treated lambs showed higher expression of myogenic genes (P<0.05) and formed more myotubes (P<0.01) when myogenic differentiation was induced invitro. In addition, invitro analysis showed that RA promoted myogenic differentiation of the skeletal muscle-derived mononuclear cells in the first 3d(P<0.05) but not at the later stage (P>0.05) as evidenced by myogenic gene expression and fusion index. Taken together, neonatal intramuscular vitamin A injection promotes lamb muscle growth by promoting the myogenic potential of satellite cells.

Inulin alleviates neuroinflammation and oxidative stress induced by perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure in female mice and offspring

Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 μg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1β, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.

Antibiotic induced restructuring of the gut microbiota does not affect oral uptake and accumulation of perfluorooctane sulfonic acid (PFOS) in rats

Perfluorooctane sulfonic acid (PFOS) is a manmade legacy compound belonging to the group of persistent per- and polyfluorinated substances (PFAS). While many adverse health effects of PFOS have been identified, knowledge about its effect on the intestinal microbiota is scarce. The microbial community inhabiting the gut of mammals plays an important role in health, for instance by affecting the uptake, excretion, and bioavailability of some xenobiotic toxicants. Here, we investigated (i) the effect of vancomycin-mediated microbiota modulation on the uptake of PFOS in adult Sprague-Dawley rats, and (ii) the effects of PFOS exposure on the rat microbiota composition. Four groups of twelve rats were exposed daily for 7 days with either 3 mg/kg PFOS plus 8 mg/kg vancomycin, only PFOS, only vancomycin, or a corn oil control. Vancomycin-induced modulation of the gut microbiota composition did not affect uptake of branched and linear PFOS over a period of 7 days, measured in serum samples. 16S rRNA amplicon sequencing of faecal and intestinal samples revealed that vancomycin treatment lowered microbial alpha-diversity, while PFOS increased the microbial diversity in vancomycin-treated as well as in non-antibiotic treated animals, possibly because an observed decrease in the Enterobacteriaceae abundance allows other microbial species to propagate. Colonic short-chain fatty acids were significantly lower in vancomycin-treated animals but remained unaffected by PFOS. Our results suggest that PFOS exposure may disturb the intestinal microbiota, but that antibiotic-induced modulation of the intestinal ecosystem does not affect systemic uptake of PFOS in rats.

Environmentally relevant doses of endocrine disrupting chemicals affect male fertility by interfering with sertoli cell glucose metabolism in mice

The growing global deterioration in several aspects of human health has been partly attributed to hazardous effects of endocrine-disrupting chemicals (EDCs) exposure. Therefore, experts and government regulatory agencies have consistently advocated for studies on the combined effects of EDCs that model human exposure to multiple environmental chemicals in real life. Here, we investigated how low concentrations of bisphenol A (BPA), and phthalates compounds affect the Sertoli cell glucose uptake/lactate production in the testis and male fertility. An EDC mixture containing a detected amount of each chemical compound in humans, called daily exposure (DE), and DE increased in magnitude by 25 (DE25), 250 (DE250), and 2500 (DE2500), and corn oil (control) were administered for six weeks to male mice. We found that DE activated estrogen receptor beta (Erβ) and glucose-regulated protein 78 (Grp 78) and disrupted the estradiol (E2) balance. In addition, DE25, DE250, and DE2500 doses of the EDC mixture via binding with Sertoli cells’ estrogen receptors (ERs) inhibited the glucose uptake and lactate production processes by downregulating glucose transporters (GLUTs) and glycolytic enzymes. As a result, endoplasmic reticulum stress (ERS), marked by unfolded protein response (UPR) activation, was induced. The accompanying upregulation of activating transcription factor 4 (ATF4), inositol requiring enzyme-1 (IRE1), C/EBP homologous protein (CHOP), and mitogen-activated protein kinase (MAPK) signaling promoted antioxidant depletion, testicular cell apoptosis, abnormal regulation of the blood−testis barrier, and decreased sperm count. Therefore, these findings suggest that human and wildlife exposure to multiple environmental chemicals can produce a wide range of reproductive health complications in male mammals.

Antioxidant, dermal and acute toxicological effects of Eucalyptus camaldulensis (Dehn-Blakely) essential oil on male Wistar rats

During the era of the COVID-19 lockdown, many Nigerians resorted to home remedies like herbal mixtures for therapy because they could not have access to orthodox medicine. Eucalyptus camaldulensis (E. camaldulensis) essential oil was one of such remedies as many believed it had the potential to treat colds, flu, sore throats, bronchitis and even prevent SARS-CoV-2 infection.&#x0D; The objective of the study is to check the antioxidant, dermal and acute toxicological effects of the E. camaldulensis essential oil. Rats were grouped into 8 of 5 each. Normal and corn oil (2ml/kg body weight) control groups. E. camaldulensis essential oil from Jos, Niger, Nasarawa, Kogi, Kwara, and Benue zones were given at 2ml/kg body weight for 14 days as well as applied on the shaved skin of the rats. No mortality was recorded in the sub-acute toxicity study at low and high doses (10mg/kg and 5000mg/kg). The levels of AST, ALT, TNF-α and IL-6 did not significantly differ from normal control rats. Lungs Investigation recorded a significant increase in the TNF-α. Antioxidant enzyme assays showed a significant increase in catalase, superoxide dismutase and glutathione-s-transferase. Histological examination showed focal inflammation with moderate cytoplasmic clearing in the liver and focal mild epidermal sclerosis of the skin. Dermal application of the oil shows no significant toxic effect except some mild inflammation (skin irritation). Oral administrations were relatively safe with mild adverse effect observed in the lung inflammatory markers.

Subchronic exposure to environmentally relevant concentrations of di-(2-ethylhexyl) phthalate differentially affects the colon and ileum in adult female mice

Di(2-ethylhexyl) phthalate (DEHP) is a large-molecular-weight phthalate added to plastics to impart versatile properties. DEHP can be found in medical equipment and devices, food containers, building materials, and children's toys. Although DEHP exposure occurs most commonly by ingesting contaminated foods in the majority of the population, its effects on the gastrointestinal tract have not been well studied. Therefore, we analyzed the effects of subchronic exposure to DEHP on the ileum and colon morphology, gene expression, and immune microenvironment. Adult C57BL/6 female mice were orally dosed with corn oil (control, n = 7) or DEHP (0.02, 0.2, or 30 mg/kg, n = 7/treatment dose) for 30–34 days. Mice were euthanized during diestrus, and colon and ileum tissues were collected for RT-qPCR and immunohistochemistry. Subchronic DEHP exposure in the ileum altered the expression of several immune-mediating factors (Muc1, Lyz1, Cldn1) and cell viability factors (Bcl2 and Aifm1). Similarly, DEHP exposure in the colon impacted the gene expression of factors involved in mediating immune responses (Muc3a, Zo2, Ocln, Il6, and Il17a); and also altered the expression of cell viability factors (Ki67, Bcl2, Cdk4, and Aifm1) as well as a specialized epithelial cell marker (Vil1). Immunohistochemical analysis of the ileum showed DEHP increased expression of VIL1, CLDN1, and TNF and decreased number of T-cells in the villi. Histological analysis of the colon showed DEHP altered morphology and reduced cell proliferation. Moreover, in the colon, DEHP increased the expression of MUC2, MUC1, VIL1, CLDN1, and TNF. DEHP also increased the number of T-cells and Type 2 immune cells in the colon. These data suggest that subchronic DEHP exposure differentially affects the ileum and colon and alters colonic morphology and the intestinal immune microenvironment. These results have important implications for understanding the effects of DEHP on the gastrointestinal system.

Investigation of combined effects of propyl paraben and methyl paraben on the hypothalamic-pituitary-adrenal axis in male rats.

The aim of this study was to investigate the endocrine-disrupting effects of methyl paraben (MeP) and propyl paraben (PrP) mixture on the hypothalamic-pituitary-adrenal axis (HPA). In this study, six experimental groups were designated. These groups included three control groups (control, corn oil control, and positive control (50mg/kg/day BPA)) and three dose groups (10, 100, and 500mg/kg/day MeP+PrP). MeP with PrP were mixed in a 1:1 ratio and administered to the 42-day-old male rats by oral gavage for 30days. At the end of the experiment, adrenocorticotropic hormone (ACTH), corticosterone and aldosterone hormones were analyzed in serum. Effects of MeP+PrP on the adrenal glands were investigated by immunohistochemical staining of 11ß hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) enzymes involved in the synthesis steps of corticosterone and aldosterone. Also, pituitary and adrenal glands were examined histopathologically. In the histopathological findings, cortical nodule, congestion, and edema were found in the tissues. In the pituitary gland, cytokeratin rings were detected in all MeP+PrP dose groups, supporting the increase of corticosterone and ACTH. Serum corticosterone, aldosterone, and ACTH hormone levels were increased in the 100 mg/kg/day MeP+PrP and BPA groups. Results obtained from immunohistochemical staining showed that increased staining parallelled increased corticosterone and aldosterone hormone levels. In summary, the results showed that exposure to the MeP+PrP mixture caused a significant increase in ACTH and corticosterone. Also, the MeP+PrP mixture caused a significant increase of CYP11B1 and CYP11B2. MeP+PrP exposure disrupts the normal HPA axis.

The protective effects of diallyl sulfide (DAS) on genotoxicity induced by benzene

Objective: To investigate the protective effect of diallyl sulfide (DAS) , against benzene-induced genetic damage in rat. Methods: In September 2018, Sixty adult male adaptive feeding 5 days, were randomly divided into six groups according to their weight. Control groups, DAS control groups, benzene model groups, benzene+low DAS groups, benzene+middle DAS groups, benzene+High DAS group, 10 in each group. Rats in the DAS and DAS control group were orally given DAS at 40, 80, 160, 160 mg/kg, blank control and benzene model groups were given corn oil in the same volume. 2 h later, the rats in the benzene model and DAS treatment groups were given gavage administration of benzene (1.3 g/kg) mixed with corn oil (50%, V/V) , blank and DAS control groups were given corn oil in the same volume. Once a day, for 4 weeks. Samples were collected for subsequent testing. Results: Compared with the blank control group, In benzene treated rat, peripheral WBC count was reduced 65.06% (P=0.003) , lymphocyte ratiowas reduced (P=0.000) , micronucleus rate was increased (P=0.000) , Mean fluorescent intensity and relative fluorescence intensity of γH2AX in BMCs were increased 32.69%、32.64% (P=0.001、0.008) , Mean fluorescent intensity and relative fluorescence intensity of γH2AX in PBLs were increased 397.70%、396.26% (P=0.000、P=0.003) respectively. Compared with the benzene model group, the WBC count increased respectively (P=0.000、0.003、0.006) and the micronucleus rate decreased (P=0.000、0.000、0.000) in the DAS groups, Mean fluorescent intensity and relative fluorescence intensity ofγH2AX in BMCs were significantly reduced in the high DAS groups (P=0.000、0.000) , Mean fluorescent intensity and relative fluorescence intensity ofγH2AX in PBLs were significantly reduced in the low, middle, high DAS groups (P=0.000、0.000) . Conclusion: DAS can effectively suppress benzene induced genotoxic damage in rats.

Multigenerational Effects of an Environmentally Relevant Phthalate Mixture on Reproductive Parameters and Ovarian miRNA Expression in Female Rats.

Phthalates are endocrine-disrupting chemicals used in many consumer products. Our laboratory previously developed an environmentally relevant phthalate mixture consisting of 6 phthalates and found that it disrupted female fertility in mice. However, it was unknown if maternal exposure to the mixture affects reproductive parameters and ovarian post-transcription in the F1 and F2 generation of female rats. Thus, we tested the hypothesis that maternal exposure to the phthalate mixture affects folliculogenesis, steroidogenesis, and ovarian microRNA (miRNA) in the F1 and F2 generations of female rats. Pregnant female rats were divided into 4 groups and orally dosed daily from gestational day 10 to postnatal day 21 with corn oil (control group), 20 μg/kg/day, 200 μg/kg/day, or 200 mg/kg/day of the phthalate mixture. Maternal exposure to the phthalate mixture impaired folliculogenesis in the F1 and F2 generations of female rats and affected steroidogenesis in the F1 generation of female rats compared to control. Further, the phthalate mixture altered ovarian expression of some genes related to the cell cycle and steroidogenesis compared to control in the F1 and F2 generations of female rats. The mixture also increased ovarian expression of rno-mir-184 that is involved with the oocyte maturation process. Collectively, our data show that maternal exposure to the phthalate mixture affects folliculogenesis and steroidogenesis in the F1 and F2 generations of female rats and alters ovarian miRNA expression in the F1 generation of female rats.

High Doses of Anacardium Occidentale Nut Shell Extract Induce Oxidative Damage in Cardiac and Renal Organs of Wistar Rats

Anacardium occidentale (Cashew) is a plant reported to show several biological activities. The aim of this study is to examine the effects of methanol extract of Anacardium occidentale nut shell on the antioxidant status and histological features in cardiac and renal tissues of rats. Shells were obtained from the nut, air-dried, pulverized, and subjected to Soxhlet extraction to obtain Anacardium occidentale nut shell extract (AONSE). Forty-five male Wistar rats were divided into nine groups (5 rats each), and given oral gavage of corn oil (Control), and 50, 100, 150, 200, 250, 300, 350 and 400 mg/kg of AONSE, every other day for twenty-eight days. After sacrifice, heart and kidney were removed and divided into two portions each; one portion was homogenized for biochemical assays, while the other was fixed in formalin for histopathology. Superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and Malondialdehyde (MDA) levels in the two organs were spectrophotometrically assayed. Histopathology of the organs was also done. The SOD and catalase were reduced in heart at high doses of AONSE relative to control. The AONSE has no significant effects on GPx, GST and MDA in the two organs, comparable to control. Photomicrographs of heart show, myocardial distortions and fibrosis, while glomerular fluid accumulation and hemorrhagic fibrosis were observed in kidney, at high doses, as against control and low doses of AONSE. This study shows that high doses of Anacardium occidentale nut shell extract could induce cytological derangements in heart and kidney of rats, possibly via oxidative mechanism.