Impact of alkaloid of Peganum harmala extract on oxidative stress biomarkers and histomorphometrics of testicular tissues in male mice (Mus musculus)

Male- and female-specific microRNA expression patterns in a mouse model of methanol poisoning.

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging

Effects of exposure to prothioconazole and its metabolite prothioconazole-desthio on oxidative stress and metabolic profiles of liver and kidney tissues in male mice

Background:Tamoxifen-inducible Cre/lox site-specific recombination technology has been widely used to generate conditional transgenic mice. As an estrogen receptor ligand, tamoxifen itself potentially affects energy metabolism, which may confound interpretation of data especially in metabolic studies. Considering sexual dimorphism, in this study, the effects of low-dose tamoxifen administration on energy metabolism, and browning of adipose tissues in female and male mice were investigated.Methods:Female and male C57/BL6 mice were injected with tamoxifen oil solution (i.p.) and then housed at both room temperature (23 ± 2 °C) and cold environment (6 ± 1 °C). Serum, brown and white adipose tissues were obtained, and the effects of tamoxifen administration on energy metabolism and the browning of adipose tissues were evaluated.Results:At 25 mg/kg body weight (BDW), tamoxifen administration for 3 alternative days decreased the percentage of inguinal and gonadal white adipose tissue weights in female mice accompanied by the up-regulation of thermogenesis in adipose tissues. In contrast, this dosage of tamoxifen did not induce noticeable changes in the energy metabolism and thermogenesis of adipose tissue in male mice under room temperature. Consistently, under cold stimulus, substantial browning of adipose tissues was observed in female mice injected with tamoxifen (50 mg/kg BDW, single injection) but not in male mice. Two-way ANOVA tests also demonstrated significant interactions between tamoxifen treatment and gender on the expression of thermogenic markers in adipose tissues.Conclusion:Tamoxifen, even at a low dose, remarkably increases thermogenesis in adipose tissues of female mice; meanwhile, such a low dose could be used in male mice for inducing gene recombination without confounding the interpretation of data related to metabolism and thermogenesis of adipose tissues.

Experimental infections with different pathogen strains give insight into pathogen life history traits. The purpose of the present study was to compare variation in tissue infection prevalence and spirochete abundance among strains of Borrelia burgdorferi in a rodent host (Mus musculus, C3H/HeJ). Male and female mice were experimentally infected via tick bite with one of 12 strains. Ear tissue biopsies were taken at days 29, 59 and 89 postinfection, and seven tissues were collected at necropsy. The presence and abundance of spirochetes in the mouse tissues were measured by quantitative polymerase chain reaction. To determine the frequencies of our strains in nature, their multilocus sequence types were matched to published data sets. For the infected mice, 56.6% of the tissues were infected with B.burgdorferi. The mean spirochete load in the mouse necropsy tissues varied 4.8-fold between the strains. The mean spirochete load in the ear tissue biopsies decreased rapidly over time for some strains. The percentage of infected tissues in male mice (65.4%) was significantly higher compared to female mice (50.5%). The mean spirochete load in the seven tissues was 1.5× higher in male mice compared to female mice; this male bias was 15.3× higher in the ventral skin. Across the 11 strains, the mean spirochete loads in the infected mouse tissues were positively correlated with the strain-specific frequencies in their tick vector populations. The study suggests that laboratory-based estimates of pathogen abundance in host tissues can predict the strain composition of this important tick-borne pathogen in nature.

Acrylamide (AA) exposure causes increased incidence of forestomach, lung, and Harderian gland tumors in male mice. One hypothesized mode of action (MOA) for AA-carcinogenicity includes genotoxicity/mutagenicity as a key event, possibly resulting from AA metabolism to the direct genotoxic metabolite glycidamide. Alternatively, altered calcium signaling (CS) has been proposed as a central key event in the MOA. To examine the plausibility of these proposed MOAs, RNA-sequencing was performed on tumor target tissues: Harderian glands (the most sensitive tumor target tissue in the rodent 2-year cancer bioassay) and lungs of AA-exposed male CD-1 mice. Animals were exposed to 0.0, 1.5, 3.0, 6.0, 12.0, or 24.0 mg AA/kg bw-day in drinking water for 5, 15, or 31 days. We observed a pronounced effect on genes involved in CS and cytoskeletal processes in both tissues, but no evidence supporting a genotoxic MOA. Benchmark dose modeling suggests transcriptional points of departure (PODs) of 0.54 and 2.21 mg/kg bw-day for the Harderian glands and lungs, respectively. These are concordant with PODs of 0.17 and 1.27 mg/kg bw-day derived from the cancer bioassay data for these tissues in male mice, respectively. Overall, this study supports the involvement of CS in AA-induced mouse carcinogenicity, which is consistent with a recently proposed CS-based MOA in rat thyroid, and with other published reports of aberrant CS in malignant tumors in rodents and humans.

Ameliorative synergistic therapeutic effect of gallic acid and albendazole against Trichinella spiralis muscular phase infection and assessment of their effects on hepatic and cardiac tissues in male mice

Because of the classification of the nickel compounds as carcinogenic substances, there is a need for in vivo tests to nickel nanoparticles (NiNPs) for observing their effects on health experimentally. Spherical NiNPs with 10 nm in diameter and 75 ppm concentration were applied for investigating their toxicities within male albino mice as an in vivo model. We randomly made sham group, control group, and 75 ppm group (with five animals in each group). Then, the nanoparticles were injected into mice intraperitonealy for 7 days and after that their lungs, liver, and spleen were removed for histopathological observations. At the end of the test, section microscopic observations of liver, spleen, and lung in sham and control groups showed normal tissues but these tissues underwent significant abnormal effects in 75 ppm group. NiNPs can cause undesirable effects in lungs, liver, and spleen tissues with same condition of this study.

The aim of the present dissertation was to study the radiation toxicity and its protection of healthy tissues in male mice. Initially, we investigated the dose-dependent protection afforded by amifostine against lethal fractionated radiation in mice. Then we studied the ‘’'autophagic flux’’ in normal tissues under different stress conditions such as: i. starvation (induction of autophagy), ii. chloroquine (inhibition of autophagy) and iii. ionizing radiation. Then, we studied the affects of ionizing radiation in autophagic response in lung and liver tissues of mice, as well and the cytoprotective effect of the amifostine on radiation-induced dysfunctional autophagy. Finally, we investigated the role of exercise on the homeostatic mechanism of autophagy after exposure to ionizing radiation in mice. The results of the first study showed that the minimum dose of amifostine to achieve 100% survival in animals after a dose of 2x6 Gy and 3x6 Gy is 25 mg/kg/day and 75 mg/kg/day, respectively. Also the 200-300 mg/kg/day amifostine provided significant protection, after 4x6 Gy as 11 out of 18 mice survived 30 days of recording. The results of the second study shown that the LC3A protein follows discrete patterns of LC3A-I and LC3A-II changes in liver, lung, kidney and heart tissues of mice, whereas the LC3B protein didn’t follow the same pattern under stressor conditions. We conclude that the endogenous LC3A processing is a major marker of autophagy flux in mouse model. The results of the third study showed that the mechanism of autophagy deregulated after 6Gy gamma radiation in normal lung cells. Deregulation was characterized by reduced LC3A mRNA transcription and accumulation of LC3A, and p62 protein, either due to defective formation of autophagosomes (lysosome fusion) or disruption of the mechanisms of degradation of autophagy-lysosomes. The results of the fourth study showed that exercise increases the levels of LC3A after irradiation in the liver and lung tissues of mice. Also, exercise failed to protect against lethal dose 2x6Gy of fractionated radiation in mice. In conclusion the present thesis supports the idea that ionizing radiation causes dysfunctional autophagy and this might be the concept of the mechanism for the radiation-indueced cell death toxicity.

The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials

Individual and joint effects of phthalate metabolites on biomarkers of oxidative stress among pregnant women in Puerto Rico

Introduction: Few studies have reported on the association between a systematic consumption of organic diet and human health effects. Pesticides, commonly used in conventional, but not in organic agriculture, could lead to generation of reactive oxygen species, indicative of oxidative stress and inflammatory responses. We aimed to evaluate the literature on the association between organic diet and biomarkers of inflammation, oxidative stress and antioxidant capacity. Methods: Using PubMed, we searched for peer-reviewed articles that examined the influence of organic diet interventions in altering key biomarkers of oxidative stress, inflammation and antioxidant capacity in human studies; in-vitro and animal studies were excluded. Results: Only 9 relevant human studies were identified. Some of the biomarkers assessed in these articles were vitamins, cytokines, malondialdehyde and C-reactive protein. For most biomarkers, no statistically (p>0.05) significant differences were observed between conventional and organic diet interventions. In three crossover studies, organic diet resulted in significant (p<0.05) changes for markers of antioxidant capacity (vitamin B12, carotenoids, flavonols, total plasma antioxidant capacity), inflammatory biomarkers (tumor necrosis factor-alpha, interleukin-6 and -1) and for biomarkers of oxidative stress (protein oxidation). Conclusions: The small number of existing studies and their heterogeneity did not provide us with solid evidence on the association of organic diet with biomarkers of oxidative stress and inflammation. Randomized controlled human trials with sufficient power and long enough windows of monitoring exposures and biomarkers of effect should be implemented.

Exposure to pesticides negatively have associated with many public health hazards infecting humans as infertility, therefore, the objective of this study was to investigate the effect of dimethoate on testicular cytoarchitecture of treated mice and on the embryos. Albino mice were divided into three groups of 9 each: the first group served as control and was given distilled water orally, whereas the second and third groups were given dimethoate at doses (0.1 and 0.2 mL dimethoate/100 mL distilled water) respectively for 20 days. At the end of the treatment, six mice from each group were weighed and sacrificed, the testis and epididymis weights were recorded, and histopathological lesions of tests were carried out. The obtained results revealed that dimethoate caused a decrease in the body and epididymis weights. Furthermore, dimethoate led to a significant decrease in the number of dead embryos and their weights. Histopathological examination demonstrated that this pesticide caused marked alterations in the microstructure of testicular tissues appeared as vacuoles, disorganization of the germinal epithelium, and degenerative changes in some seminiferous tubules as well as its effect on the embryos, therefore, more efforts should be conducted to protect our environment and health from these detrimental compounds and the search for safe methods for insect control.

Benzo(a)pyrene (B[a]P) can induce somatic mutations, whereas its potential to induce germ cell mutations is unclear. There is circumstantial evidence that paternal exposure to B[a]P can result in germ cell mutations. Since DNA adducts are thought to be a prerequisite for B[a]P induced mutations, we studied DNA adduct kinetics by (32)P-postlabeling in sperm, testes and lung tissues of male mice after a single exposure to B[a]P (13 mg/kg bw, by gavage). To investigate DNA adduct formation at different stages of spermatogenesis, mice were sacrificed at Day 1, 4, 7, 10, 14, 21, 32, and 42 after exposure. In addition, DNA repair deficient (Xpc(-/-)) mice were used to study the contribution of nucleotide excision repair in DNA damage removal. DNA adducts were detectable with highest levels in lung followed by sperm and testis. Maximum adduct levels in the lung and testis were observed at Day 1 after exposure, while adduct levels in sperm reached maximum levels at approximately 1 week after exposure. Lung tissue and testis of Xpc(-/-) mice contained significantly higher DNA adduct levels compared to wild type (Wt) mice over the entire 42 day observation period (P < 0.05). Differences in adduct half-life between Xpc(-/-) and Wt mice were only observed in testis. In sperm, DNA adduct levels were significantly higher in Xpc(-/-) mice than in Wt mice only at Day 42 after exposure (P = 0.01). These results indicate that spermatogonia and testes are susceptible for the induction of DNA damage and rely on nucleotide excision repair for maintaining their genetic integrity.

To determine, in a chronic dosing study, the oral toxicity potential of the test substances, enclomiphene citrate (ENC) and zuclomiphene citrate (ZUC), when administered to male mice by oral gavage. Mice were divided into five treatment groups. Group I, placebo; Group II, 40 mg/kg body weight/day ENC; Group III, 4 mg/kg/day ENC; Group IV, 40 mg/kg/day ZUC; Group V, 4 mg/kg/day ZUC. Serum samples and tissues were obtained from each mouse for analysis and body weights were measured. In this chronic dosing study in mice, profound effects on Leydig cells, epididymis, seminal vesicles, and kidneys were seen, as well as effects on serum testosterone, follicle-stimulating hormone and luteinising hormone levels that were associated with ZUC treatment only. Treatment with the isolated enclomiphene isomer had positive effects on testosterone production and no effects on testicular histology. The present study suggests that an unopposed high dose of zuclomiphene can have pernicious effects on male mammalian reproductive organs. The deleterious effects seen when administering ZUC in male mice, justifies the case for a monoisomeric preparation and the development of ENC for clinical use in human males to increase serum levels of testosterone and maintain sperm counts.