Antineoplastic drugs in environmentally relevant concentrations cause endocrine disruption and testicular dysfunction in experimental conditions.

5-fluorouracil (5-FU) and methotrexate (MTX) are among the most widely consumed antineoplastic drugs worldwide. These drugs are known as emerging pollutants, once after consumption are excreted by feces and/or urine in a mixture of compounds and metabolites, entering the aquatic environment due to low efficiency in drug removal by effluent treatment plants. Considering that these substances may interact with the DNA, causing metabolic and morphological changes, leading to cell death, the present study aimed to investigate the potential impact of a long-term exposure to these antineoplastic drugs in environmentally relevant concentrations, on testicular morphophysiology of rats. Male Wistar rats (70 days old) were distributed into 4 groups (n = 10 / group): control, received only vehicle; MTX, received methotrexate at 10ngL-1 in drinking water; 5-FU received 5-fluorouracil at 10ngL-1 in drinking water; and MTX+ 5FU, received the combination of MTX and 5-FU at 10ngL-1 each. The treatment period was from postnatal day (PND)70 to PND160, when the animals were euthanized for evaluation of testicular toxicity and changes in endocrine signaling. In these experimental conditions, both drugs acted as endocrine disruptors causing cytotoxic effects in the testes of exposed rats, altering the structural pattern of seminiferous tubules and leading to oxidative stress even at environmental concentrations.

Low concentrations of sodium arsenite induce hepatotoxicity in prepubertal male rats.

Arsenic (As) can contaminate air, soil, water, and organisms through mobilization of natural mineralogical deposits or anthropogenic actions. Inorganic-As compounds are more toxic and widely available in aquatic environments, including drinking water reservoir catchments. Since little is known about its effects on prepubertal mammals, the present study focused on it. Hence, As was administered through drinking water to male Wistar rats from postnatal day 23 to 53. Negative control group received vehicle only (filtered water); As 1 group received AsNaO2 at 0.01 mg L-1 and As2 group received AsNaO2 at 10 mg L-1 . It was investigated hepatic and renal toxicity of AsNaO2 (ie, histopathology and apoptosis analysis), as well as its mutagenicity (ie, micronucleus test in liver and bone marrow), cytotoxicity (ie, frequency and type of erythrocytes in blood), and genotoxicity (ie, comet assay in blood). Also, As determination was performed in hepatic and renal tissues. Data obtained revealed that immature organisms present a pattern of arsenic accumulation similar to that observed in adults, suggesting similarity in metabolic processes. In addition, liver showed to be an important target tissue for As toxicity in these experimental conditions, exhibiting infiltrate of defense cells, DNA damages, and increased apoptosis rates.

Arsenic exposure during prepuberty alters prostate maturation in pubescent rats.

Arsenic is a widely dispersed chemical compound in the environment and has been associated with the development of some diseases and different types of cancer. Little is known about the action of arsenic compounds on prostate development during prepuberty and puberty. This study evaluated prostate morphophysiology after sodium arsenite exposure during prepubertal period in rats. Male Wistar rats at PND23 were randomly distributed into three experimental groups (n = 10/group). The Ctrl group (filtered drinking water); As1 group (0.01 mg/L of NaAsO2); As2 group (10.0 mg/L of NaAsO2) that received the diluted solution in drinking water from PND23 to PND53. Histological and molecular analyzes showed developmental delay in the As1 group and important morphophysiological alterations in As2 group. The results showed that exposure to NaAsO2 during prepuberty compromised structural and functional maturation of the prostate in pubertal rats at both doses evaluated in this study.

Prepubertal exposure to low doses of sodium arsenite impairs spermatogenesis and epididymal histophysiology in rats.

For the first time, juvenile toxicity of inorganic arsenic (As) was investigated in male rats, focusing on reproductive effects. As is a metalloid naturally occurring in the environment, being the inorganic forms the most toxics. Contaminated drinking water and agricultural products are the main prospectors of intoxication for general population. In the present study, Wistar male rats (21 days old) were distributed into three groups (n = 10/group): control (received vehicle-filtered drinking water), As1 (received AsNaO2 at 0.01 mg L-1 ) and As2 (received AsNaO2 at 10 mg L-1 ). The animals were euthanized on PND 53. Testicular damages increased in As1 and As2 compared to control (ie, presence of vacuolization, acidophilic cells, and epithelium degeneration). Testicular interstitium of As1 and As2 presented fluid's increase and intense inflammatory infiltration. In the epididymis there was reduction of sperm amount in the lumen, besides epithelium areas presenting cribriform aspect in As1 and As2, exfoliation of cells in the light (in As1) and vacuoles (in As2). In epididymis interstitium, inflammatory infiltrates were observed in initial segment of As1 and As2. AsNaO2 changed immunolabeling pattern for androgen receptor in epididymis of As2, although serum testosterone levels was statistically comparable to control. Mass spectrometry revealed higher As concentrations in testis and epididymis of As2 compared to As1 and Control. These results indicate compromise of spermatogenesis and epididymal histophysiology in AsNaO2 -treated animals, possibly impairing sperm quality and fertility in long-term, even at low levels of exposure. Investigations about the reversibility of reproductive damages are necessary to better understand the mechanisms of As reproductive toxicity.