INVESTIGATION OF PHARMACOLOGICAL PROFILE OF SOME ENDOCRINE DISRUPTORS IN MALE RATS

Abstract

Endocrine disrupting chemicals (EDC) are the natural or synthetic compounds which mimic or inhibit the actions of endogenous hormones or modulate the synthesis of latter and are said to adversely affect the normal functioning of the endocrine system. They can be broadly categorized as (anti) androgenic, (anti)estrogenic or (anti) progestagenic chemicals depending on their effects on the production or functions of those steroids (i.e. androgens, estrogens, progesterone respectively). EDC may enter into the physiological system of animals/humans through the diet or occupational exposure and have been related with the occurrence of a number of hormone-sensitive disease/disorders like reduced fecundity, abnormal fetal development, delayed onset of puberty, cryptorchadism, abnormal lactation, testicular dysfunction and even various types of cancers The present work describes action of two major pesticides: Chlordane and Monocrotophos. We investigated chlordane, monocrotophos for endocrine disruptions and reproductive toxicity in animal model (in vivo). Our aim was to evaluate the hazardous effects of chlordane and monocrotophos in order to establish a relationship between the exposure to these insecticides (through any modes) and occurrence of various human diseases. Results showed that oral administration of chlordane and monocrotophos caused a significant reduction in the overall body weight along with weight of testis and accessory sex organs. However, the weight of the liver was increased significantly. Negative fertility was observed at high dose of chlordane and monocrotophos. Motility of sperms in cauda epididymides was decreased markedly after oral administration of chlordane and monocrotophos at all dose levels. Sperm density in the testis and cauda epididymides was decreased significantly in rats treated with chlordane and monocrotophos at all dose levels. A significant decrease was observed in serum testosterone concentration in the chlordane and monocrotophos treated rats at higher dose levels which was indicative of its anti-androgenic activities. Total erythrocyte count (TEC), haemoglobin concentration and haematocrit values were significantly decreased at various dose levels of chlordane and monocrotophos treatment. Whereas the total leukocyte count (TLC) was increased in chlordane and monocrotophos exposed rats at all the dose levels. Blood urea and blood sugar, bilirubin concentration, serum protein were significantly increased. Serum phospholipids, Serum cholesterol, HDL-Chol, LDL-Chol and VLDL-Chol levels were increased at all the dose levels. Degenerative changes in the histoarchitecture of testis and reduced amount of secretion in seminal vesicle and prostate was also observed. The histoarchitecture of testis was altered markedly. Inhibition of spermatogenesis, shrunken and damaged seminiferous tubules with increased interstitial spaces, degenerated and vacuolated Sertoli cells, presence of vacuoles in the epithelium, disruption of Leydig cells were conspicuous. Epididymes showed reduced number of spermatozoa in the lumen of caput and cauda regions after the treatment with chlordane and monocrotophos. The epithelial lining was regressed. Histopathologically size of the liver was found to be increased (hypertrophy) and various histopathological alterations were observed in the kidney which includes glomerulonephritis, glomeruloscleroses, odenema, pycnotic nuclei and glomerulus deposits. The results of the present study revealed that the administration of chlordane and monocrotophos insecticides induces reproductive toxicity as well as hepato-nephrotoxicity in male albino rats. In which mating test showed 100% negative fertility that is the state of sterility. Low concentration of spermatozoa in testis and cauda epididymides and reduction in number of spermatogenic elements in testis reflects antispermatogenic nature of chlordane and monocrotophos insecticides. Increase in acid phosphatase, aspartate, alanine transferase and bilirubin indicates the hepatotoxic action of insecticides due to cellular damage. Increase blood urea and pathological alterations further suggests the chlordane and monocrotophos induced intoxication on the structure and function of kidney.