Avaliação do efeito da melatonina em ratas prenhes após exposição a doses subletais de herbicidas

Abstract

The inadequate use of herbicides may cause serious and sometimes chronic poisoning due to long exposure to low levels. Herbicides may also be teratogenic, mutagenic, cancerigenous agents and endocrine disruptors, with the occurrence of neurodegenerative diseases and reproduction disorders. Several studies have shown that melatonin has antioxidant, anti-inflammatory and immune-modulating qualities, besides affecting the reproduction system. It is a beneficent agent in the intoxication by herbicides even though no reports are extant on the use of melatonin against intoxications by Glyphosate-Roundup® alone or associated to Paraquat. Current analysis investigates the effect of melatonin on the reproduction and hepatic aspects in female rats exposed to sub-lethal doses of the herbicide Paraquat (50 mg/kg) and/or Glyphosate-Roundup® (500 mg/kg) of body weight, alone or associated. Thirty-five pregnant rats were used, randomly divided into 7 groups with 5 animals each. Group I (control/saline), groups (II and III) exposed to Paraquat and Glyphosate-Roundup® respectively, the IV group exposed to the associated herbicide, while the rats of the groups (V and VI ) were exposed to the herbicides alone and group (VII) above the associated herbicides, however the groups (V, VI and VII) were simultaneously treated with melatonin (10 mg/kg body weight). Both exposure as treatment with melatonin was during the first third of pregnancy. Thus, the hematological profile, function and hepatic oxidative stress, reproduction parameters such as body weight gain, ovaries weight, number of implantation sites, corpora lutea, pre-implantation losses, implantation rates and histopathology of implantation sites and liver were analyzed. Results post-exposure to associated or single herbicides revealed decrease in body and ovary weights, number of implantation sites, implantation rate (the implantation rate (number of implanted embryos compared with the number of corpora lutea), total number of corpora lutea, percentage increase of pre-implantation losses. The hematological profile revealed a reduction of erythrocytes in hemoglobin concentrations, in hematocrit rates, increase in total counts of leucocytes, in the number of segmented neutrophils, eosinophils and decrease in lymphocytes. Moreover, decrease in serum levels of albumin, increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP), high levels of reactive compounds to thiobarbituric acid (TBARS) and reduction in the levels of reduced glutathione (GSH) were reported in biochemical and hepatic oxidative stress analyses. The histopathological analysis of the implantation sites revealed the disorganization of blastocyte and degeneration of cytotrophoblasts within the blastocyte cavity, whilst in histochemical analysis was observed reduction number of uterine natural killer cells (uNKs). Morphometry revealed decrease endometrial parameters of superficial and glandular epithelium, as well as the diameter of the endometrial glands. In the histopathological analysis of liver samples was observed the presence of necrotic hepatocytes, portal and central lobular inflammatory infiltrate and congestion of sinusoid capillaries. Treatments with melatonin provided results significantly similar to those in control animals, with the exception of serum albumin levels in rats associated group (Paraquat 50 mg/kg) and/or Glyphosate-Roundup® 500 mg/kg of body weight), which remained low. Treatment with melatonin at a dose of 10 mg/kg of body weight is a protecting agent against experimentally induced maternal and embryo poisoning by herbicides. Body weight, reproduction, hematological, biochemical parameters maintenance and hepatic oxidative stress was reduced.