Perfil inflamatório e oxidativo de testículos e epidídimos de camundongos adultos expostos ao clorotalonil

Abstract

Among the pesticides consumed in Brazil, chlorothalonil (CHL) is the fifth most commercialized active ingredient and the third within the organochlorine class. Evidence from the literature demonstrates that CHL is capable of inducing nephrotoxicity, carcinogenesis, allergic dermatitis, asthma, mucosal irritation, and reproductive toxicity. However, studies investigating the effects of low-dose CHL exposure on reproductive parameters remain scarce. Therefore, the present study aimed to evaluate whether exposure to CHL during adulthood influences testosterone and estradiol levels, as well as oxidative parameters in the testes and inflammatory parameters in the epididymis of male mice. The experimental protocol was approved by the Animal Use Ethics Committee of the Federal University of Triângulo Mineiro (CEUA-UFTM; approval no. 23/2023). Twenty-four adult male C57BL/6 mice, with an initial age of 50 days, were randomly assigned to three experimental groups: control (CTRL), which received only the vehicle (water); chlorothalonil 1 mg/kg (CHL1); and chlorothalonil 10 mg/kg (CHL10). The compound was administered orally by gavage for 50 consecutive days. At the end of the experimental period, the animals were weighed and euthanized by intraperitoneal overdose of ketamine and xylazine. Testes, epididymides, and blood samples were collected and processed according to the specific analytical procedures. In the epididymides, the cytokines IL-1β, TNF-α, IFN-γ, and IL-10 were quantified by enzyme-linked immunosorbent assay (ELISA). In the testes, oxidative stress markers (AOPP, MDA, GSH, and TEAC) were evaluated, and relative gene expression of androgen receptor (AR) and estrogen receptor alpha (ER-α) was assessed by RT-qPCR. In addition, serum testosterone and estradiol concentrations were determined using commercial ELISA kits. CHL exposure resulted in a reduction of TNF-α, IFN-γ, and IL-10 levels in the caput region of the epididymis. No changes were observed in oxidative damage markers AOPP and MDA. Conversely, GSH levels were reduced in both CHL-exposed groups, and total antioxidant capacity (TEAC) was increased in the CHL10 group. Relative gene expression of AR and ER-α was increased in the CHL1 group. Serum estradiol and testosterone levels were increased exclusively in the group exposed to the highest dose, whereas the lower-dose group exhibited hormone concentrations similar to those of the control group. In conclusion, exposure to low doses of chlorothalonil alters the antioxidant profile of the testes in adult mice, induces a dysregulated epididymal inflammatory response, and acts as an endocrine disruptor.