Eugenol reduces serum testosterone levels and sperm viability in adult Wistar rats.

Eugenol is the main constituent of clove extract. It is a remarkably versatile molecule incorporated as a functional ingredient in several food products and widely applied in the pharmaceutical industry. Men consume natural products enriched with eugenol for treating sexual disorders and using as aphrodisiacs. Nevertheless, there is no information about the impact of eugenol intake on the reproductive parameters of healthy males. Therefore, we provided 10, 20, and 40 mg kg-1 pure eugenol to adult Wistar rats for 60 days. Testis, epididymis, and spermatozoa were analyzed under microscopic, biochemical, and functional approaches. This phenolic compound did not alter testicular and epididymal biometry and microscopy. However, 20 and 40 mg kg-1 eugenol reduced serum testosterone levels. The highest dose altered lactate and glucose concentrations in the epididymis. All the eugenol concentrations diminished CAT activity and MDA levels in the testis and increased FRAP and CAT activity in the epididymis. Epididymal sperm from rats receiving 10, 20, and 40 mg kg-1 eugenol presented high Ca2+ ATPase activity and low motility. In conclusion, eugenol at low and high doses negatively impacted the competence of epididymal sperm and modified oxidative parameters in male organs, with no influence on their microscopy.

High doses of eugenol cause structural and functional damage to the rat liver.

Eugenol is a phenolic compound found in clove extract and extensively used in traditional medicine. It is unclear whether its intake can cause positive or negative effects on liver morphology and physiology in healthy individuals. Thus, we aimed to evaluate liver parameters of rats treated with 10, 20, and 40 mg kg-1 eugenol. After 60 days of treatment, liver samples were collected and analyzed by biometric, histological, biochemical, and oxidative analyses. Our results showed that 10, 20, and 40 mg kg-1 eugenol did not alter body and liver weights, serum and hepatic ALT levels and catalase, glutathione-s-transferase, total, Ca2+, and Mg2+ ATPases activities in treated animals. However, 20 and 40 mg kg-1 eugenol reduced Na+/K+ ATPase pump activity and blood glucose levels. They also increased hepatic glycogen content, superoxide dismutase activity, ferric reducing antioxidant power, and nitric oxide and malondialdehyde levels. Still, 20 and 40 mg kg-1 eugenol caused structural and functional damage to the liver tissue of eugenol-treated rats. We concluded that 10 mg kg-1 eugenol is a safe dose for consumption in long-term treatment for rats. Doses higher than 20 mg kg-1 lead to hepatic damage that can impair vital processes of liver functionality.

Synthesis of cinnamic acid ester derivatives with antiproliferative and antimetastatic activities on murine melanoma cells.

Melanoma is the most aggressive skin cancer, and its incidence has continued to rise during the past decades. Conventional treatments present severe side effects in cancer patients, and melanoma can be refractory to commonly used anticancer drugs, which justify the efforts to find new potential anti-melanoma drugs. An alternative to promote the discovery of new pharmacological substances would be modifying chemical groups from a bioactive compound. Here we describe the synthesis of seventeen compounds derived from cinnamic acid and their bioactivity evaluation against melanoma cells. The compound phenyl 2,3-dibromo-3-phenylpropanoate (3q) was the most effective against murine B16-F10 cells, as observed in cytotoxicity and cell migration assays. Simultaneously, this compound showed low cytotoxic activity on non-tumor cells. At the highest concentration, the compound 3q was able to trigger apoptosis, whereas, at lower concentrations, it affected the cell cycle and melanoma cell proliferation. Furthermore, cinnamate 3q impaired cell invasion, adhesion, colonization, and actin polymerization. In conclusion, these results highlight the antiproliferative and antimetastatic potential of cinnamic acid derivatives on melanoma.

Short-term intake of deltamethrin-contaminated fruit, even at low concentrations, induces testicular damage in fruit-eating bats (Artibeus lituratus).

Deltamethrin (DTM) is a pyrethroid insecticide widely used for agricultural purposes. Exposure to DTM has proven to be harmful to humans, but whether low, environmental concentrations of this pesticide also poses a threat to wild mammals is still unknown. In Neotropical areas, bats play important roles in contributing to forest regeneration. We investigated the effects of DTM exposure on the reproductive function of male Neotropical fruit-eating bats (Artibeus lituratus), known for contributing to reforestation through seed dispersal in Neotropical Forests. Bats were assigned to 3 groups: control (fed with papaya); DTM2 (fed with papaya treated with DTM at 0.02 mg/kg) and DTM4 (fed with papaya treated with DTM at 0.04 mg/kg) for seven days. Bats from DTM2 and DTM4 groups showed increased testicular levels of nitric oxide and superoxide dismutase and catalase activities. The germinal epithelium from DTM4 bats showed non-viable cells and cell desquamation, indicating microscopic lesions and Leydig cells atrophy. Our results demonstrate the onset of cell degeneration that may affect the reproductive function in DTM exposed bats.

Green tea infusion prevents diabetic nephropathy aggravation in recent-onset type 1 diabetes regardless of glycemic control.

ETHNOPHARMACOLOGICAL RELEVANCE: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies. AIM: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes. MATERIAL AND METHODS: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney. RESULTS: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment. CONCLUSION: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia.

Effect of eugenol treatment in hyperglycemic murine models: A meta-analysis.

Diabetes is a highly prevalent health condition affecting many people worldwide. In vitro studies have described the positive effects of cloves and its major compound, eugenol, in the treatment of diabetes. However, it is unclear whether the effects of this compound are negative, neutral, or positive, on hyperglycemic animals. Therefore, a meta-analytical review was conducted to determine the magnitude of effects of eugenol on variables directly and indirectly related to diabetes. This study revealed that eugenol treatment decreased the glucose levels and the activity of carbohydrate-metabolizing enzymes, ameliorated the lipid profile, and reduced the oxidative, renal, and hepatic damages in hyperglycemic rodents. Moreover, eugenol alleviated the weight loss and restored the activity of the antioxidant defense system. Insulin levels was not affected by eugenol treatment. Also, mixed model analyses revealed that the use of purified or non-purified eugenol and the concentrations administered significantly affected the treatment outcome. In conclusion, our findings indicate that eugenol may have potential therapeutic effects in the treatment of diabetes. Furthermore, this study can direct future preclinical and clinical trials, with important implications for human health.

Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma.

The Serine/arginine-rich protein kinases (SRPK) are involved in pre-mRNA splicing control through the phosphorylation of the SR protein family of splicing factors. Over the last years, several studies have shown the relevance of SRPK for human cancers and their potential as promising drug targets. In this context, we have previously selected three trifluoromethyl arylamides (named here as SRVIC24, SRVIC30 and SRVIC36) with improved in vitro antileukemia effect and ability of impairing the cellular activity of SRPK. Given the increasing amount of reports on the implication of these kinases in metastatic cancers, in this study, we have evaluated the antimetastatic effect of these compounds and the known SRPK inhibitor (SRPIN340) on a murine model of metastatic melanoma. The compounds were able to impact the melanoma cell metastatic behavior by decreasing migration, invasion, adhesion, and colony formation in in vitro assays. Also, they presented antimetastatic in vivo activity, without apparent signs of systemic toxicity after treatments, as revealed by the histology of organs and analysis of key serum biochemical markers. Moreover, the effect of the treatments on SRPK1 nuclear translocation and SR protein phosphorylation was observed. Finally, molecular docking studies were carried out to gain structural information on the SRPK-compound complexes. Together, these data suggest that SRPK pharmacological inhibition should be considered as an interesting therapeutic strategy against metastatic cancers.

Synthesis and antimetastatic activity evaluation of cinnamic acid derivatives containing 1,2,3-triazolic portions.

It is herein described the preparation and evaluation of antimetastatic activity of twenty-six cinnamic acid derivatives containing 1,2,3-triazolic portions. The compounds were prepared using as the key step the Copper(I)-catalyzed azide (A)-alkyne (A) cycloaddition (C) (CuAAC reaction), also known as click reaction, between alkynylated cinnamic acid derivatives and different benzyl azides. The reactions were carried in CH2Cl2/H2O (1:1 v/v) at room temperature, and the triazole derivatives were obtained in yields ranging from 73%99%. Reaction times varied from 5 to 40 min. The identity of the synthesized compounds was confirmed by IR and NMR (1H and 13C) spectroscopic techniques. They were then submitted to in vitro bioassays to investigate how they act over metastatic behavior of murine melanoma. The most potent compound, namely 3-(1-benzyl-1H-1,2,3-triazol-4-yl)propyl cinnamate (9a), showed significant antimetastatic and antiproliferative activities against B16-F10 cells. In addition, gelatin zymography and molecular docking analyses pointed to the fact that this compound has potential to interact with matrix metalloproteinase 9 (MMP-9) and MMP-2, which are directly involved in melanoma progression. Therefore, these findings suggest that cinnamic acid derivatives containing 1,2,3-triazolic portions may have potential for development of novel candidates for controlling malignant metastatic melanoma.

Fertility in male rats: Disentangling adverse effects of arsenic compounds.

Arsenic impairs male reproductive functions. However, it is not clear whether different arsenic compounds similarly affect fertility. In this study, we compared the impact of sodium arsenite and arsenate on sperm quality and fertility. After 56 d exposure, male Wistar rats were mated and pregnant females were evaluated by fertility indexes. Clearly, exposure to 10 mg/L arsenite reduced daily sperm production via H2O2 overproduction and germ cells loss. Animals from this group also showed a decrease in epididymal sperm counts and percentage of sperm with intact membranes. Moreover, they presented low fertility potential and high preimplantation loss. In contrast, 10 mg/L arsenate caused oxidative stress in testis, mineral imbalance in epididymis, and sperm membranes damage, with no effects on fertility. Both arsenic compounds at 0.01 mg/L altered reproductive parameters. We concluded that arsenite is more harmful than arsenate to sperm quality and male fertility, with negative influences in early pregnancy.

Effects of sodium arsenate and arsenite on male reproductive functions in Wistar rats.

Arsenic (As), in the form of trivalent arsenite or pentavalent arsenate, is a ubiquitous toxic compound naturally occurring in the environment. This study aimed to evaluate the impact of two different forms of inorganic As on reproductive parameters following oral exposure. Adult Wistar male rats were exposed to sodium arsenite or arsenate at concentrations of 0.01 mg/L or 10 mg/L for 56 d in drinking water. Sodium arsenite at both concentrations and sodium arsenate at 10 mg/L produced reduction in daily sperm production, in number of spermatids in the testis, and in sperm in the epididymal caput/corpus regions. Changes in epididymal morphometry were variable and region specific. Total and progressive sperm motility and sperm morphology did not differ markedly between controls and animals exposed to As. The body and reproductive organs weights, as well as testosterone concentration, remained unchanged among all groups. In conclusion, As exposure in drinking water over 56 d produced damage in male reproductive functions in adult rats, suggesting that fertility problems might occur. Therefore, additional studies need to be undertaken to investigate potential mechanisms underlying sodium arsenite- and arsenate-induced disturbances in fertility and reproductive performance.