{"id":5853,"date":"2015-12-28T10:04:33","date_gmt":"2015-12-28T10:04:33","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=5853"},"modified":"2020-04-25T06:10:11","modified_gmt":"2020-04-25T06:10:11","slug":"the-effect-of-herbicide-paraquat-and-organophosphate-pesticide-malathion-on-changes-of-sex-hormones-in-female-rats","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol8no2\/the-effect-of-herbicide-paraquat-and-organophosphate-pesticide-malathion-on-changes-of-sex-hormones-in-female-rats\/","title":{"rendered":"The Effect of Herbicide Paraquat and Organophosphate Pesticide Malathion on Changes of Sex Hormones in Female Rats"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

By production of chemical pesticides,\u00a0human decides to control own environment to\u00a0protect agricultural product cultivate for food supply,\u00a0against pests. The antiquity of chemical opposition\u00a0with pests and herbal diseases returns to more than\u00a0a thousand years before Christ1. Paraquat is an\u00a0herbicide in the category of bipyridylium2. As a\u00a0powerful herbicide due to unique characteristics,\u00a0paraquat has remarkable consumption and\u00a0production in all around the word. Its chemical\u00a0formula is N, N\u2019-dimethyl-4, 4\u2019-bipyridinium\u00a0dichloride. Paraquat is mainly used as herbicide\u00a0and causes serious lung damage and other injuries\u00a0in mammals.\u00a0This herbicide is highly toxic for human\u00a0(especially with delayed toxicity mechanism to\u00a0human) and animals. This kind of toxicity is
\nassociated with mitochondrial and microsomal\u00a0oxidation and reduction systems3. The mechanism\u00a0of paraquat toxicity is often related to production of\u00a0superoxide anions, which can lead to production\u00a0of large amounts of reactive oxygen species (ROS),\u00a0such as hydrogen peroxide and superoxide anions.\u00a0The two free radicals are considered as two major\u00a0toxicants. These radicals are highly toxic and are\u00a0intensively combined with macromolecules and\u00a0cause serious damages to various organs4, 5. As a\u00a0strong peripheral toxic compound, paraquat affects\u00a0on the growth and development of amphibians.\u00a0Followed by orally absorption, paraquat\u00a0accumulates in all important body organs,\u00a0particularly the lungs (more than 10 times higher\u00a0than plasma) as an optional member and due to\u00a0the high volume of distribution. So that in case of\u00a0severe poisoning, death occurs from respiratory\u00a0failure due to pulmonary edema and fibrosis6. The\u00a0impact of paraquat and its mechanism in\u00a0reproductive system of male rats is decreased\u00a0weight of male reproductive systems (includes\u00a0testes, epididymis, seminal vesicles, and prostate),\u00a0as well as reduced number of sperms, cell division,\u00a0and spermatogonial cells7. Researches performed\u00a0on bacteria, mice and human revealed that\u00a0paraquat has no mutagenic and carcinogenic\u00a0effects. However, it weakens the immune system\u00a0and endometriosis. Reduced number of sex cells\u00a0and considerable shrinkage in Bulb\/c race of mice\u00a0is caused by paraquat, as well8.\u00a0Malathion is introduced in 1950 as the first\u00a0phosphorous compounds of mammals. Rapid\u00a0decomposition in body into non-toxic compounds\u00a0followed by consumption is the important\u00a0prominence of organophosphorous compounds.\u00a0Unlike chlorinated organic pesticides, this\u00a0compound does not accumulate in body tissues of\u00a0living organisms and biological cycles1. Its scientific\u00a0name is malathion or carbofos and its trade name\u00a0is malathion and malathiosol1. Malathion is derived\u00a0from phosphorodithioic acid1. Its utilization for a\u00a0certain period may be toxic for some cells such as\u00a0T cells9. Liver tissue is a candidate for receiving of\u00a0malathion most effects10. This toxic compound also\u00a0causes disturbance of DNA in body11, induction of\u00a0free radicals production and oxidative stress in the\u00a0brain, and increased activity of anti-oxidant\u00a0enzymes12. Use of lethal and sub-lethal dose of this\u00a0poison can also increase fatty acids, glycerol, and\u00a0lipase activity in tested tissues and this can have a\u00a0negative impact on reproductive activity and causes\u00a0decline in the population13.\u00a0By inhibition of acetylcholinesterase\u00a0enzyme, steroidogenesis process is inhibited by\u00a0malathion, too1. Followed by absorption of\u00a0organophosphorus (OP) pesticides in body, they\u00a0undergo numerous bio-transformation reactions.\u00a0Since OP compounds are lipophilic, they permeate\u00a0to skin readily. The bio-transformation reactions are\u00a0mainly derived toward formation of polar\u00a0compounds to achieve the ability of exertion from\u00a0kidneys. OP compounds in biological terms may\u00a0convert to some metabolites which their toxicity\u00a0changes determinately15.\u00a0Given to the above as well as widespread\u00a0use of paraquat and malathion and various direct\u00a0and indirect effects of these toxins on reproductive\u00a0system, so this study is aimed to investigate the\u00a0impact of an herbicide (paraquat) and an\u00a0organophosphate pesticide (malathion) on\u00a0changes of sex hormones in female rats.<\/p>\n

Methods<\/strong><\/p>\n

This study was conducted in vitro and\u00a0completely random. All ethical use of animals was\u00a0observed in this study. A total number of 80 adult\u00a0female Wistar rats weighing 20015 g and at 100-\u00a0120 days of age were produced from Razi Vaccine\u00a0and Serum Research Institute of Shiraz. The rats\u00a0were then transported to Jahrom and kept for 2\u00a0weeks in Animal House of Islamic Azad University\u00a0under in vitro condition, including 212 \u00daC and a\u00a0cycle of 12 hours of light and 12 hours of darkness.\u00a0Malathion insecticide and paraquat pesticide were\u00a0prepared from Moshkfam and Alafkosh Companies,\u00a0respectively. The toxins were injected\u00a0intraperitoneally for 14 days. Since malathion and\u00a0paraquat are soluble in saline, so malathion and\u00a0paraquat lethal doses were determined 80 mg per\u00a0kilogram of body weight and 8 mg per kilogram of\u00a0body weight, respectively. The rats were then divided\u00a0randomly as follows:<\/p>\n

Control<\/strong><\/p>\n

The rats in this group were kept in normal\u00a0condition and without receiving any medications.<\/p>\n

Blank<\/strong><\/p>\n

The rats in this group received saline\u00a0intraperitoneally.\u00a0Paraquat receiving groups\u00a0Experimental P1: the rats in this group\u00a0intraperitoneally received paraquat at 1 mg\/kg body\u00a0weight.\u00a0Experimental P2: the rats in this group\u00a0intraperitoneally received paraquat at 2 mg\/kg body\u00a0weight.\u00a0Experimental P3: the rats in this group\u00a0intraperitoneally received paraquat at 4 mg\/kg body\u00a0weight.<\/p>\n

Malathion receiving groups<\/strong><\/p>\n

Experimental M1: the rats in this group\u00a0intraperitoneally received malathion at 10 mg\/kg of\u00a0body weight.
\nExperimental M2: the rats in this group\u00a0intraperitoneally received malathion at 20 mg\/kg of\u00a0body weight.
\nExperimental M3: the rats in this group\u00a0intraperitoneally received malathion at 40 mg\/kg of\u00a0body weight.<\/p>\n

After the injections, all rats were\u00a0anesthetized and dissected and blood samples\u00a0were obtained directly from their hearts using insulin\u00a0syringe (5 cc). Subsequent to separation of blood\u00a0serum, the concentrations of LH, FSH, estrogen,\u00a0and progesterone hormones were measured by\u00a0ELISA method in the laboratory of Jahrom\u2019s Medical\u00a0Science University. One-way analysis of variance\u00a0(abbreviated one-way ANOVA) was used for\u00a0comparison between treatments. P<0.05 was\u00a0considered as significant level. SPSS version 15\u00a0was also used for data analysis and to perform\u00a0statistical tests.<\/p>\n

Results<\/strong><\/p>\n

The obtained results related to changes\u00a0of sex hormones in paraquat receiving groups are\u00a0as follows. As listed in Table 1, it is clear that the\u00a0amounts of LH hormone in all the experimental\u00a0groups do not show significant changes compared\u00a0with the control group. However, FSH levels in all\u00a0groups reveal a significant increase compared with\u00a0the control group (P<0.05). There is no significant\u00a0change in estrogen levels in all the experimental P\u00a0groups. A significant decrease is observed in\u00a0progesterone hormone levels in the experimental\u00a0P1 group compared with the control group. However,\u00a0this amount shows a significant increase in the\u00a0experimental P2 group compared with the control\u00a0group and no significant change is observed in the\u00a0experimental P3 group.\u00a0The obtained results related to changes\u00a0of sex hormones in malathion receiving groups are\u00a0as follows. According to Table 2, LH hormone levels\u00a0in all the experimental groups do not show a\u00a0significant change compared with the control group.\u00a0FSH hormone levels in all groups show a significant\u00a0increase compared with the control group (p<0.05).\u00a0Estrogen levels in the experimental M1 and M2\u00a0groups show significant decrease compared with\u00a0the control group (p<0.05). However, this amount\u00a0in the experimental M3 group do not show a\u00a0significant change compared with the control group.\u00a0Progesterone hormone levels show a significant\u00a0reduction compared with the control group\u00a0(p<0.05).<\/p>\n\n\n\n
\"table<\/td>\nTable 1: Sex hormones changes in the experimental groups<\/strong>
\nreceiving paraquat (the experimental P groups)<\/strong><\/p>\n

Click here to View\u00a0Table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Discussion<\/strong><\/p>\n

A- Interpretation of results related to\u00a0changes in sex hormones in the experimental\u00a0groups receiving paraquat (the experimental P\u00a0groups) With increasing population in human\u00a0society, preparation of food supplies is impossible\u00a0without use of advanced scientific farming. In\u00a0modern agriculture, people have to use pesticides,\u00a0herbicides and chemical fertilizers, as well. All of\u00a0these pesticides, herbicides and chemical fertilizers\u00a0while serving humans are somehow cause\u00a0problems. One of the toxins is paraquat which its\u00a0biochemical parameters and mechanisms have not\u00a0been identified accurately.\u00a0Studies have shown that oxidative stress\u00a0plays an important role in pathogenesis of several\u00a0diseases such as cancer, diabetes, atherosclerosis,\u00a0and lung disease and cataracts16. Oxidative stress\u00a0is caused by free radicals and mitochondria are\u00a0known as the main location for production of free\u00a0radicals 17. Mitochondria are targets of choice for\u00a0paraquat toxicity in animal and herbal tissues18. On\u00a0the other hand, lipids peroxidation increases\u00a0adverse effects such as increased stiffness of\u00a0membrane, reduction of intracellular materials,\u00a0decreased in fluidity of membrane, and osmotic\u00a0fragility19. Paraquat also reduces the amounts of\u00a0glutathione and glucose 6-phosphate\u00a0dehydrogenase, while increases superoxide\u00a0glutathione, glutathione peroxidase catalase, and\u00a0superoxide. This reflects defense and impact on\u00a0antioxidant system of rats20.\u00a0Performed studies have shown till now\u00a0some impacts of paraquat such as histopathological\u00a0changes in rats21 and ovarian and testicular atrophy\u00a022. Paraquat impacts investigation on different\u00a0generations of particular race of hen during certain\u00a0periods revealed that paraquat caused reduced
\nfertility, and ovaries and fallopian tubes weight loss,\u00a0as well as impairment in newborn baby chicks23.\u00a0Other performed studies on paraquat and\u00a0glyphosate effects on ovaries and testes of\u00a0amphibians found that paraquat inhibits 17-beta\u00a0estradiol, resulting impairment in steroidogenesis\u00a0pathway. This may be caused by oxygenic reagents\u00a0or reactive oxygen species (ROS)24. So it can be\u00a0concluded that if an ovarian tissue is damaged,
\nthen it will face with impairment in the secretion of\u00a0estrogen and progesterone hormones. This\u00a0impairment appears in the form of decreased or\u00a0increased levels of the hormones. On this basis,\u00a0significant reduction of progesterone hormone\u00a0levels in the experimental P1 group compared with\u00a0the control is quite logical. In this study, the estrogen
\nlevels increase in the experimental P1 group and\u00a0decrease in the experimental P2 and P3 groups,\u00a0however these changes are not significant\u00a0compared with the control group. Changes of LH\u00a0and FSH hormones may initially seem to be due to\u00a0increased amount of GnRH which increases blood\u00a0serum FSH, but since these changes have no effect
\non blood serum levels of LH, they could not be\u00a0effective in increase of GnRH. FSH levels show\u00a0significant increase in all the experimental P groups\u00a0compared with the control group (p<0.05).\u00a0According to the researches of Hemayatkhah\u00a0Jahromi et al. in 2008, the concentration of these\u00a0hormones reduced in adult male rats. This is\u00a0contrary to what we have achieved in this study\u00a0which could be due to the released free radicals\u00a0and lipid peroxidation (1-captopril). This causes\u00a0tissue changes and as a result impairments in\u00a0secretion of hormones. This difference also may\u00a0depend to gender of rats.\u00a0B- Interpretation of results related to\u00a0changes in sex hormones in the experimental\u00a0groups receiving malathion (the experimental M\u00a0groups) So far, most researches have been done\u00a0in the terms of the effect of organophosphorous\u00a0pesticides with various doses on different organs\u00a0and on different animals and each of which\u00a0obtained different results. The results obtained inthis research that show malathion effect on ovaries \u00a0of rats can complete available data about the effects\u00a0of this pesticide on various species investigated
\nprevious.\u00a0Organophosphorous pesticides have\u00a0alkylation properties and thus can affect on nuclear\u00a0DNA25. Malathion increases malondialdehyde\u00a0levels in ovarian tissue that may be caused by\u00a0release of free radicals as a result of body lipid\u00a0metabolisms. On the other hand, malathion causes\u00a0ovarian tissue damages and weight loss; with\u00a0increased doses, malathion toxicity reduces\u00a0healthy follicles and increases the number of atretic\u00a0follicles. It also changes corpus luteum26. Other\u00a0studies show that increased levels of\u00a0malondialdehyde and lower antioxidant defense\u00a0system in body can lead to destruction of cells 27.\u00a0So this conclusion that levels of estrogen and\u00a0progesterone hormones significantly decreased is\u00a0quite logical since these two hormones secrete from\u00a0ovaries and any tissue damages to ovaries impairs\u00a0the secretion of these hormones. Studies also\u00a0reveal that malathion does not significantly change\u00a0levels of FSH and 17-beta estradiol in dairy cows.\u00a0However, progesterone level was significantly\u00a0decreased after injection of this pesticide. Malathion\u00a0induces oxidative stress and production of free radicals and increases the activity of antioxidant\u00a0enzymes28. Malathion effects on concentrations of\u00a0acetylcholinesterase (AChE) and 5-delta, 3-beta\u00a0hydroxysteroid and phosphate dehydrogenase\u00a0were invstigated in a study. This pesticide induces\u00a0chromosomal aberrations in somatic cells (bone\u00a0marrow) and early sexual cells (primary\u00a0spermatocytes)30, 31. It should be noted that ovarian\u00a0is the secretion site of estrogen and progesterone\u00a0hormones, while gonadotropin hormones are\u00a0released from pituitary gland. There is no research\u00a0about malathion impact on pituitary tissues. On the\u00a0other hand, ovarian hormones influence on\u00a0secretion of pituitary gonadotropin secretion during\u00a0the estrous cycle. Of course, the main role of\u00a0hypothalamus should not be ignored.<\/p>\n\n\n\n
\"table<\/td>\nTable 2: Sex hormones changes in the experimental groups\u00a0<\/strong>receiving malathion (the experimental M groups)<\/strong><\/p>\n

Click here to View Table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Conclusion<\/strong><\/p>\n

According to this study, it can be told that\u00a0malathion pesticide and paraquat herbicide can\u00a0have devastating effects on female rats reproductive\u00a0indicators and these effects may be extended in\u00a0lesser extent to human. Of course, in this case the\u00a0use of pesticides as well as the amount of exposure\u00a0to it is very important. So care must be taken in\u00a0generalizing of this research findings to human and\u00a0possible experiments should be carefully done.<\/p>\n

References<\/strong><\/p>\n

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