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It has been hypothesized that oils containing high levels of omega-3 polyunsaturated fatty acids, such as canola and fish oil, could counteract some of the adverse effects induced by phthalates. In the present study, the influence of different oily vehicles on di-butyl phthalate (DBP)-induced testicular toxicity and lipid profile was investigated. Pregnant Wistar rats were treated by oral gavage from gestation days 13 to 20 with DBP (500 mg/kg/day) diluted in three different vehicles: corn, canola or fish oil. Male fetuses were analyzed on gestation day 20. DBP exposure lowered intratesticular testosterone levels and anogenital distance, regardless of the vehicle used. The percentage of seminiferous cords containing multinucleated gonocytes and cord diameter was increased in DBP-exposed groups, compared with vehicle controls, with no difference between the three DBP-exposed groups. Clustering of Leydig cells was seen in all DBP groups. Lipid profile indicated that administration of canola and fish oil can increase the content of omega-3 fatty acids in rat testis. However, content of omega-3 was diminished in DBP-treated groups. Overall, our results indicate that different oily vehicles did not alter fetal rat testicular toxicity induced by a high DBP dose. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) constitutes a very aggressive type of breast cancer with few options of cytotoxic chemotherapy available for them. A chemotherapy regimen comprising of doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel, known as AC-T, is approved for usage as an adjuvant treatment for this type of breast cancer. In this study we aimed to elucidate the role of KIF11 in TNBC progression throughout its inhibition by two synthetic small molecules containing the DHPM core (dihydropyrimidin-2(1H)-ones or -thiones), with the hypothesis that these inhibitors could be an interesting option of antimitotic drug used alone or as adjuvant therapy in association with AC. For this purpose, we evaluated the efficacy of DHPMs used as monotherapy or in combination with doxorubicin and cyclophosphamide, in Balbc-nude mice bearing breast cancer induced by MDA-MB-231, having AC-T as positive control. Our data provide extensive evidence to demonstrate that KIF11 inhibitors showed pronounced antitumor activity, acting in key points of tumorigenesis and cancer progression in in vivo xenograft model of triple negative breast cancer, like down-regulation of KIF11 and ALDH1-A1. Moreover, they didn't show the classic peripheral neuropathy characterized by impaired mobility, as it is common with paclitaxel use. These results suggest that the use of a MAP inhibitor in breast cancer regimen treatment could be a promising strategy to keep antitumoral activity reducing the side effects., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare., (Copyright: © 2021 Guido et al.)

Coagulant fixatives and paraffin embedding were widely used in the past for histomorphometrical evaluations of the human testis under physiological and pathological conditions. However, new methods are applied nowadays using better combinations of fixatives and plastic resins as embedding media, improving cell and tissue structural preservation. In an attempt to compare old and new data, the present study evaluated histomorphometrical data obtained from human testis after three different histological processing methods: Bouin/paraplast, glutaraldehyde/glycol methacrylate and glutaraldehyde/araldite. The morphometrical parameters were not affected by glutaraldehyde fixation after both resin embedding (methacrylate or araldite). On the other hand, Bouin/paraplast embedding lead to tissue shrinkage, which could give rise to misinterpretations on the measurements performed. Since some germ and somatic cells recognition do not depend upon high resolution techniques, counting of such cell types could be performed even using routine Bouin/paraplast protocols. Thus, the morphometrical analyses relying on cell recognition were not affected by the methods here applied, however, when metric measurements were applied, the obtained results could not be promptly compared. However, if the study requires confident spermatogonial identification for kinetics evaluation, glutaraldehyde/araldite processing is highly recommended.

Ethnopharmacological Relevance: Paffia spp (Amaranthacea) has a widespread use of in Brazil as a possible hormonal supplement and a substitute of Panax ginseng, although information on its reproductive effects is missing., Aim of the Study: To evaluated possible anabolic-androgenic or anti-androgenic effects of Pfaffia glomerata (PG) extract using intact eight-months-old male rats and pre-pubertal castrated rats., Materials and Methods: Three different dose levels of PG (8.5, 30 and 85 mg/kg/day) were administered to eight-months-old rats for 28 days or to castrated males for 7 days (Hershberger assay). In the experiment with intact animals, 24h fecal samples were collected for quantification of fecal metabolites of androgens throughout treatment. At the end of the treatment period, animals were euthanized for evaluation of serum testosterone, reproductive organ weights, number of spermatids per testis, diameter of seminiferous tubules and cross-sectional area of soleus muscle fibers. In the Hershberber assay, androgenic or anti-androgenic effects were evaluated by the weights of androgen-dependent tissues: ventral prostate, seminal vesicle, glans penis and levator ani muscle/bulbocavernosus muscle., Results: No effects were observed in the concentrations of fecal metabolites of androgens monitored during the treatment of intact eight-months-old rats. Moreover, at the end of treatment, no changes were seen in any of the investigated parameters. In the Hershberger assay, the PG extract did not induce androgenic or anti-androgenic effects at the dose levels tested. Significant effects were only observed in animals treated with testosterone and testosterone plus flutamide, which were used as positive controls for androgenicity and anti-androgenicity, respectively., Conclusions: At the dose levels tested, PG extract does not induce anabolic-androgenic or anti-androgenic effects in rats., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

In utero exposure to the antivirals acyclovir and ganciclovir has been reported to induce gross structural defects in rat offspring. The present study investigated the effects of maternal antiviral treatment on gestation day 10 on reproductive and nonreproductive organs in male rat offspring with a particular focus on the testes. Vehicle and two doses of acyclovir and ganciclovir, 75 and 300 mg/kg, were administered to rat dams. The total doses were fractioned into three subcutaneous applications (3 × distilled water, 3 × 25 mg/kg, and 3 × 100 mg/kg) that were administered on gestation day 10 at 8:00 a.m., 1:00 p.m., and 6:00 p.m. The antiviral concentrations were measured in the serum of the dams 1 h after the last administration. Exposure to 300 mg/kg ganciclovir induced germ cell deficiency in both fetal and adult testes, an effect that was not seen in any other treatment group. Adult rats exposed in utero to this high ganciclovir dose exhibited Sertoli cell-only tubules intermingled with seminiferous tubules that displayed a normal size and normal cell counts, alterations that resemble focal Sertoli cell-only syndrome in humans. The serum concentrations of ganciclovir were markedly higher than those of acyclovir, particularly at the high dose tested. However, although 300 mg/kg acyclovir did not induce germ cell deficiency, other specific effects were seen in exposed animals, including incomplete eye opening and reduced thymus weight.

Ethnopharmacological Relevance: The use of medicinal plants for the treatment of diseases usually comes from the belief that they present low toxicity due their natural origin. However, it is necessary a toxicological and pharmacological evaluation for these plants. Tropaeolum majus is a medicinal plant used in popular medicine to treat several diseases, including cardiovascular disorders, urinary tract infections and asthma. Even though several studies proved its therapeutic effects, there are few toxicological studies with this species., Aim of the Study: The present study was carried out to evaluate the subchronic toxicity of the hydroethanolic extract obtained from leaves of T. majus (HETM) in Wistar rats., Material and Methods: Male and female Wistar rats received three doses of HETM (75, 375 and 750 mg/kg) for 28 days. After the treatments biochemical, hematological and histopathological parameters were analyzed., Results: No significant alterations in the animal's body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys and spleen were observed., Conclusions: These results demonstrate the absence of subchronic toxicity due to oral treatment with HETM for 28 days in Wistar rats. However, other toxicological studies are necessary to evaluate the total safety of this plant., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)