Users Online: 643

Home Print this page Email this page Small font sizeDefault font sizeIncrease font size

Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Login 
     

   Table of Contents      
ORIGINAL ARTICLE
Year : 2011  |  Volume : 1  |  Issue : 2  |  Page : 179-183

A pathomorphological study of the sublethal toxicity of cypermethrin in Sprague Dawley rats


1 Department of Animal and Veterinary Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Sultanate of Oman;Center of Excellence in Pathology, College of Veterinary and Animal Sciences, Thrissur, Kerala,India
2 Center of Excellence in Pathology, College of Veterinary and Animal Sciences, Thrissur, Kerala,India
3 Center of Excellence in Pathology and Department of Veterinary Pharmacology and Toxicology, College of Veterinary and Animal Sciences, Thrissur, Kerala, India

Date of Submission23-Jan-2011
Date of Acceptance06-Mar-2011
Date of Web Publication23-Aug-2011

Correspondence Address:
Remya R Nair
Department of Animal and Veterinary Sciences, College of Agricultural and Marine Sciences, PO.Box 34, PC. 123, Sultan Qaboos University, Sultanate of Oman

Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0738.84211

Rights and Permissions
   Abstract 

Introduction : A study was undertaken to investigate the potential toxic effects of cypermethrin in adult Sprague Dawley male rats, with particular emphasis on its effect on the nervous and digestive systems. Materials and Methods: The clinical signs, gross and histological alterations were analyzed, to study the effects of different doses of cypermethrin. Results: Medium and high doses produced nervous signs in animals. Gross lesions were observed in the intoxicated groups, such as, bloat, congestion of lungs, heart, brain, pulmonary haemorrhage, and degenerative changes in the liver and kidneys. Microscopically effects on all organs were mild-to moderate degenerative changes at the low-dose level. Medium- and high-dose intoxicated groups revealed necrotic changes, extensive haemorrhages, congestion in organs like liver, kidney, and lungs apart from the changes observed in low-dose group animals. Conclusions: The text to abstract): The present study reveals that cypermenthrin can produce toxic effects in mammals at sublethal doses.

Keywords: Clinical signs, cypermethrin, histopathology, sublethal toxicity


How to cite this article:
Nair RR, Abraham MJ, Lalithakunjamma C R, Nair N D, Aravindakshan C M. A pathomorphological study of the sublethal toxicity of cypermethrin in Sprague Dawley rats. Int J Nutr Pharmacol Neurol Dis 2011;1:179-83

How to cite this URL:
Nair RR, Abraham MJ, Lalithakunjamma C R, Nair N D, Aravindakshan C M. A pathomorphological study of the sublethal toxicity of cypermethrin in Sprague Dawley rats. Int J Nutr Pharmacol Neurol Dis [serial online] 2011 [cited 2019 Jun 17];1:179-83. Available from: http://www.ijnpnd.com/text.asp?2011/1/2/179/84211


   Introduction Top


Pesticides play a multipurpose role in the control of insects/pests and rodents in modern agriculture. Widespread use of pesticides in agriculture and livestock production has posed potential health hazards, not only to livestock and wildlife, but also to fishes, birds, mammals, and even human beings. [1] The synthetic pyrethroids constitute an unique group of insecticides having a pyrethrin-like structure, with better performance characteristics, and account for over 30% of insecticides used globally. [2] Cypermethrin, a recent synthetic pyrethroid is extensively used for plant protection and control of ectoparasites of domestic animals. [3] Some of the toxic actions of cypermethrin have been reported earlier, but the effect of oral administration of sublethal doses of cypermethrin on the gastrointestinal tract and nervous system together has not been reported. The toxicity study of cypermethrin in gingely oil vehicle in rats has not been studied. Therefore, the present study has been undertaken to know the sublethal effect of cypermethrin on the clinical signs, gross pathology, and histopathology of the brain, spinal cord, liver, esophagus, stomach, intestine, kidney, lungs, and heart, following repeated doses in rats.


   Materials and Methods Top


Adult male Sprague Dawley rats weighing 200 ± 3 g procured from Small Animal Breeding Station, at the College of Veterinary and Animal Sciences, Mannuthy, were used for the study. The rats were maintained on identical feeding and management practices in the laboratory for one week, before commencement of studies. The animals were randomly divided into five groups of eight each and designated as groups I to V. Technical grade cypermethrin was dissolved in 2 ml of gingely oil at the specified dose rates (40 mg/kg, 80 mg/kg, and 120mg/kg body weight) and administered orally, using a gastric tube, to rats of group III, group IV and group V, respectively, daily, for 21 days. Group II animals were administered 2 ml gingely oil daily orally for 21 days, using a gastric tube, to evaluate the effect of feeding gingely oil. Group I animals were maintained without any treatment. This protocol was approved by the Institutional Animal Ethics Committee, College of Veterinary and Animal Sciences, Thrissur.

Symptoms shown by all intoxicated animals were noted regularly. At the end of the experiment, the animals were sacrificed and weighed. Detailed postmortem examinations were conducted and gross lesions were noted. Brain, spinal cord, oesophagus, stomach, intestine, liver, kidney, lungs, and heart were collected for histopathology. The brain and spinal cord were fixed in neutral buffered formalin and the other tissues were fixed in 10% formalin. The sections were cut in 4 micron thickness and stained with the routine Hematoxylin and Eosin stain. [4]


   Results and Discussion Top


Mortality pattern

The group treated with 120 mg/kg body weight (group V) of cypermethrin showed 100% mortality within three to seven days. The medium-dose group, which was given 80 mg/kg body weight of cypermethrin, showed 75% mortality, and most of the deaths occurred within six to ten days. Animals of the lowest-dose group and the control groups did not show any mortality, indicating that mortality was due to cypermethrin toxicity. Manna et al.,[5] reported that LD 50 of α cypermethrin is 145 mg/kg body weight and 100% mortality in the highest dose group agrees with this finding.

Clinical signs

The clinical sign observed in the low-dose group was loss of body weight during the first few days of intoxication. Later the animals adapted and gradually their body condition improved. Another sign noticed during the early days of intoxication was gradual development of hind limb extensor tone followed by recovery. Other signs noticed were increased startle response, salivation, and somnolence. The medium-dose group exhibited signs such as burrowing behavior, increased startle response, salivation, somnolence, seizures, and gradual development of hind limb extensor tone. Finally choreoathetosis developed and the animal became recumbent, showing labored breathing, gasping, and death. The highest-dose group animals exhibited increased startle response, seizures, somnolence, and salivation initially, but later showed loss of righting reflex, lateral recumbency, labored breathing, gasping, and death. Similar signs were observed by Aldana et al.,[6] and Manna et al.,[5] in cypermethrin toxicity studies in rats, at different dose levels. Cypermethrin, a cyanopyrethroid, produces type II syndrome or choreoathetosis/salivation (CS) syndrome in rodents, characterized by signs such as initial pawing and burrowing behavior, salivation, seizures, increased startle response, and abnormal locomotion involving hind limbs. [7] All these suggest that cypermethrin primarily affects the nervous system and the primary neurotoxic target sites are the voltage-dependent sodium channels in the excitable membrane. The prolonged sodium current induced by the pyrethroids, results in pronounced repetitive activity, which is manifested as the CS syndrome. [8] Near lethal doses can give rise to axonal degeneration in the peripheral nerve, closely resembling Wallarian degeneration, but this effect is inherently reversible and is seen only at dose levels that produce prolonged and severe motor signs. Current prolongation for a longer period can cause in-coordination, choreoathetosis, seizures, and can have a direct effect on the skeletal and cardiac muscles and salivary glands. [9]

Gross pathology

The gross lesions in the lowest-dose group and medium group that survived until the end of experiment were bloat, congestion of the lungs, brain, and gastric mucosa, with mild degenerative changes in the liver and kidneys. Similar lesions with extensive pulmonary haemorrhage were observed in the medium- and highest-dose group of animals that died during the experiment. Manna et al.,[5],[10] observed bloat, haemorrhages in the stomach, intestine, and lungs, in both single dose and repeated dose toxicity studies of cypermethrin in rats. No gross morphological changes were observed in the visceral organs by Luty et al.,[11] in a study of toxicity of dermally applied cypermethrin in rats. In crossbred calves, cypermethrin intoxication produced congestion and/or haemorrhages on the auriculoventricular groove of the heart, lungs, mucosal surface of the intestine, cortex of the kidney, and brain (Patel et al., 2000). Haemorrhages in the liver, kidneys, lungs, ventricles, and endocardium of male dwarf goats treated with high doses (0.8 and 1.6%) of cypermethrin were reported by Khan et al.[1]

Histopathology

The lesions in the cerebrum of the treated groups were gliosis, perineuronal vacuolation, perivascular vacuolation, and neuronal degeneration [Figure 1], and the severity of the lesions was slightly different between the groups. The highest dose group, that is, group V, revealed discontinuity and shrinkage of the Purkinje cells in the cerebellum [Figure 2] and congestion in the meninges apart from the above-mentioned lesions. In cypermethrin-intoxicated rats, pyknosis of the Purkinje cells and disappearance of some of the cells in the cerebellum was observed by Luty et al.[11] Pyknosis of neurons was observed by Latuszynska et al.,[12] and Sayim et al.,[2] in their studies on cypermethrin-intoxication in rats. Congestion and degenerative changes in the brain were reported by Patel et al.,[1] and Muthuviveganandavel et al.,[13] in calves and rats, respectively. Manna et al.,[5],[10] and b) reported congestion and haemorrhages in the brain of rats intoxicated with single and repeated doses of cypermethrin. In cypermethrin-intoxicated rats, Grewal et al.,[14] observed neuronal degeneration and necrosis in the cerebrum. Spinal cord lesions were observed only in group III animals and they included large neuronal degeneration, perineuronal vacuolation, and vacuolation of the white matter [Figure 3]. Vijverberg and Bercken, [8] demonstrated histopathological lesions in the peripheral nerves and occasionally in the brain and spinal cord of rats, mice, and hamsters receiving lethal or near-lethal oral doses of pyrethroids. Many pesticide agents are reported to cause variable changes in the brain on repeated exposure, which have been related to hypoxia, hypoglycemia, and / or damage to cell ion homeostasis. [14]
Figure 1: Cerebrum-Perineuronal vacuolation and perivascular vacuolation. 80 mg / kg body weight. H and E x400.

Click here to view
Figure 2: Cerebellum-Shrinkage (a) and loss of Purkinje cells (b); 120 mg / kg body weight. H and E x400.

Click here to view
Figure 3: Spinal cord-Spongiosis of white matter, perineuronal vacuolation. 40 mg / kg body weight. H and E x400

Click here to view


The most consistent lesions in the liver of animals, of all treatment groups, were varying degrees of degenerative changes and vascular changes. In some areas, the degenerative changes extended up to necrotic changes. In the livers of the group III animals, Kupffer cell hyperplasia was pronounced. These findings were in agreement with those observed in cypermethrin toxicity in rats by Grewal et al.,[14] Muthuviveganandavel et al.,[13] Yavasoglu

et al.,[15] Manna et al.,[5],[10] and Luty et al.[11] All had conducted experiments in albino rats, but the dosage and route of administration of cypermethrin were different. In crossbred cow calves, cypermethrin intoxication produced moderate congestion of the sinusoids and hepatic vasculature, and the hepatocytes showed tiny vacuoles along with increased granularity in the cytoplasm of the liver. [1] In male dwarf goats, necrosis, condensed/pyknotic nucleus, and regeneration of the hepatocytes was observed by Khan et al.[16] Cypermethrin metabolized in the liver via the hydrolytic ester cleavage and an oxidative pathway by the cytochrome P-450 microsomal enzyme system, which caused oxidative stress by reducing the activity of superoxide dismutase and glycogen level, leading to hepatic degeneration and necrosis. [5] Nair et al.[17] reported elevation in serum aspartate aminotransferase(AST) and alanine amino transferase (ALT) levels in rats treated with cypermethrin and the pathological changes in liver can be correlated with the elevation in serum enzyme levels.

The oesophagus in all intoxicated groups revealed no lesions. In the stomach, the highest dose group (group V) revealed superficial erosion with a presence of RBCs and lysed cells in the non-glandular portion of the stomach. Manna et al.,[5],[10] observed desquamation and necrosis of the epithelium of the stomach of rats intoxicated with single and repeated doses of cypermethrin. Diffuse hyperplasia of the goblet cells and inflammatory cell infiltration into the villous epithelium of the intestine was observed in group III and group IV, whereas, diffuse necrosis of the villous epithelium was observed in group V. Patel et al.,[1] , reported congestion in the submucosa and mucosa, degenerative changes in the enterocytes, and foci of desquamation in cypermethrin-intoxicated calves. Desquamation of epithelium and fibrous tissue proliferation with celluar infiltration were observed in the intestine of cypermethrin-intoxicated male dwarf goats. [16]

In the group III animals, the lungs revealed varying degrees of pulmonary congestion and edema, while those in groups IV and V exhibited pulmonary edema, varying degrees of pulmonary congestion, and haemorrhages. These were the lesions observed in most of the toxicity studies with cypermethrin. Patel et al.,[1] reported mild-to-moderate congestion, edema, hemorrhage, and focal areas of emphysema in cypermethrin-intoxicated calves. Manna et al.,[5],[10] reported the same lesions in rats intoxicated with single and repeated doses of cypermethrin. Congestion, hemorrhage, and thickening of the interalveolar septa of rats intoxicated with cypermethrin was reported by Grewal et al.[14]

Varying degrees of degeneration extending to necrosis was observed in the tubular epithelial cells of animals of all treatment groups. Other lesions encountered in group III were congestion and diffuse atrophy of the glomeruli. In the medium- and high-dose groups, other than the lesions mentioned earlier, multiple haemorrhages in both the cortical and medullary tubules, besides the interstitium, were evident. Luty et al.,[11] observed parenchymatous degeneration in the tubular epithelium of rats. Latuszynska et al.,[18] observed infiltration of mononuclear cells between proximal tubules and around blood vessels in rats intoxicated with cypermethrin and chlorpyrifos. Patel et al.,[1] reported vacuolation of cytoplasm and rarefaction in the parenchyma of tubular epithelial cells of the kidneys, along with intense congestion, in cypermethrin-intoxicated calves. Lakkawar et al.[19] , found hyalinization of the tubular epithelium of the kidneys in rabbits in cypermethrin toxicity. Destruction of the tubular epithelium was observed by Muthuviveganandavel et al.[13] Lower dose produced sloughing off the renal tubular epithelial cells, whereas, a higher dose produced mild haemorrhage, sloughing off epithelial cells, shrinkage of glomeruli, and necrosis of renal tubules in rats treated with cypermethrin, and suggested that any process that interferes with the structural integrity of the glomeruli and renal tubules can cause a nephrotoxic effect. [14]

The lowest dose group (group III) revealed no microscopic lesions in the heart. Haemorrhage and congestion with focal myolysis [Figure 4] were observed in the myocardium of animals in groups IV and V. Patel et al.,[1] found congestion and haemorrhagic foci, with loss of cross striations and eosinophilic appearance of cardiomyocytes in crossbred calves intoxicated with cypermethrin. Muscle bands were observed to appear in patches and blood vessels were found to have ruptured in the myocardium of rats with cypermethrin toxicity. [13] Histopathological studies on the heart showed that lower dose of cypermethrin had no apparent adverse effect, but a higher dose produced haemorrhages, disruption in branching structure, with loss of striations, and early necrotic changes in the myocardium of rats. [14] The toxicity of cypermethrin can be compared with doxorubicin, a potent chemotherapeutic drug, that induces moderate necrosis and changes in biochemical parameters in rats treated with it. [20]
Figure 4: Heart-Intermuscular haemorrhage (a) and myolysis (b); 80 mg / kg body weight; H and E ×400.

Click here to view



   Conclusions Top


Even though pyrethroid pesticides are stated to be less toxic to mammals, the present study reveals that it is can affect various vital organs and produce toxic signs in mammals. Therefore, proper care should be taken, while using pyrethroid compounds such as pesticides/insecticides.


   Acknowledgment Top


The authors are thankful to the Dean of the College of Veterinary and Animal Sciences for providing facilities to conduct the research, and also to Makham Pharmaceuticals for providing technical grade cypermethrin for the research.

 
   References Top

1.Aldana L, Mejia EG, Craigmill A, Tsutsumi V, Borunda JA, Panduro A, Rincon AR. Cypermethrin increases apo A-1 and apo B mRNA but not hyperlipidemia in rats. Toxicol Lett 1998;95:31-9.  Back to cited text no. 1
    
2.Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. 5 th ed. USA: Churchill Livingstone; 2002. p. 63.  Back to cited text no. 2
    
3.Garg SK. Veterinary Toxicology. New Delhi: CBS Publishers and Distributors; 2006. p. 176.  Back to cited text no. 3
    
4.Grewal KK, Sandhu GS, Kaur RR, Brar RS, Sandhu HS. Toxic impact of cypermethrin onbehaviour and histology of certain tissues of albino rats. Toxicol Intl 2010;17:94-8.  Back to cited text no. 4
    
5.Khan A, Faridi HA, Ali M, Khan MZ, Siddique M, Hussain I, Ahmed M. Effects of cypermethrin on some clinico- hemato- biochemical and pathological parameters in male dwarf goats (Capra hircus). Exp Toxicol Pathol 2009;61:151-60.  Back to cited text no. 5
    
6.Lakkawar AW, Chattopadhyay SK, Somvanshi R. Experimental cypermethrin toxicity in rabbits- a clinical and pathomorphological study. Folia Veterinaria 2004;48:3-8.  Back to cited text no. 6
    
7.Latuszynska J, Luty S, Halliop J, Przylepa E, Tochman A, Obuchowska D, Korczak E. Studies of toxicity of dermally absorbed Nurelle D 550 EC preparations. Ann Agric Environ Med 1999;6:151-9.  Back to cited text no. 7
    
8.Latuszynska J, Luty S, Raszewski G, Roda MT, Przebirowska D, Przylepa E, Haratym A. Neurotoxic effects of dermally applied chlorpyriphos and cypermethrin in Wistar rats. Ann Agric Environ Med 2001;8:163-70.  Back to cited text no. 8
    
9.Luty S, Latuszynska J, Halliop J, Tochman A, Obu Chowska D, Prazylepa E, Korezak E. Toxicity of dermally applied alpha cypermethrin in rats. Ann Agric Environ Med 1998;5:109-15.  Back to cited text no. 9
    
10.Manna S, Bhattacharya D, Basak DK, Mandal TK. Single oral dose toxicity study of á cypermethrin in rats. Indian J Pharmacol 2004;36:25-8.  Back to cited text no. 10
  Medknow Journal  
11.Manna S, Bhattacharya D, Mandal TK, Das S . Repeated dose toxicity of alfa cypermethrin in rats. J Vet Sci 2004;5:241-5.  Back to cited text no. 11
    
12.Muthuviveganandavel V, Muthuraman P, Muthu S, Srikumar K. A study of low dose cypermethrin induced histopathology, lipid peroxidation and marker enzyme changes in male rat. Pestic Biochem Physiol 2008;91:12-6.  Back to cited text no. 12
    
13.Nair RR, Abraham MJ, Nair ND , Lalithakunjamma CR , Aravindakshan CM. Hematological and biochemical profile in sublethal toxicity of cypermethrin in rats. Int J Bio Med Res 2010; 1: 211-14.  Back to cited text no. 13
    
14.Patel BJ, Singh SP, Sharma SN, Joshi DV. Clinico- pathomorphological studies on induced cypermethrin toxicity in crossbred cow calves. Indian J Anim Sci 2000;70:925-8.  Back to cited text no. 14
    
15.Ray DE, Forshaw PJ. Pyrethroid Insecticides: Poisoning, Syndromes, Synergies and Therapy. Clin Toxicol 2000;38:95-101.  Back to cited text no. 15
    
16.Sayim F, Yavasoglu NU, Uyamkgil Y, Aktug H, Yavasoglu A, Turgut M. Neurotoxic effects of cypermethrin in Wistar rats: A haematological, biochemical and histopathological study. J Health Sci 2005;51:300-7.  Back to cited text no. 16
    
17.Varshneya C, Singh T, Sharma LD, Bahga HS, Garg SK. Immunotoxic responses of cypermethrin, a synthetic pyrethroid insecticide in rats. Indian J Physiol Pharmacol 1992;36:123-6.  Back to cited text no. 17
    
18.Vijay T, Sarumathy K, Palani S, Sakthivel K, Rajan D. Cardioprotective, antioxidant activities and phytochemical analysis of Gmelina arborea (GA) in doxorubicin induced myocardial necrosis in rats. Proceedings of International Congress on Nutrition in Cardiovascular Diseases (Healthy Heart '10) .Int J Nutr Pharmocol Neurological Diseases 2011;1: 21-2  Back to cited text no. 18
    
19.Vijverberg HP, Bercken JV. Neurotoxicological effects and mode of action of pyrethroid insecticides. CRC Rev Toxicol 1990; 21:105-26.  Back to cited text no. 19
    
20.Yavasoglu A, Sayim F, Uyamkgil Y, Turgut M, Yavasoglu NU. The pyrethroid cypermethrin induced biochemical and histological alterations in rat liver. J Health Sci 2006;52:774-80.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


This article has been cited by
1 Protective effect of a-lipoic acid against a-cypermethrin-induced changes in rat cerebellum
H. Elsawy,M.A. Al-Omair,A. Sedky,L. Al-Otaibi
Journal of Chemical Neuroanatomy. 2017; 86: 52
[Pubmed] | [DOI]
2 Ameliorating effect of Phoenix dactylifera on lambda cyhalothrin induced biochemical, hematological and hepatopathological alterations in male wistar rats
Mani Ramadhas,Krishnan Palanisamy,Munisamy Sudhagar,Vinayagam Magendira Mani
Biomedicine & Aging Pathology. 2014;
[Pubmed] | [DOI]
3 Effects of melatonin on changes in cognitive performances and brain malondialdehyde concentration induced by sub–chronic co–administration of chlorpyrifos and cypermethrin in male Wister rats
Idris Sherifat Banke,Ambali Suleiman Folorunsho,Bisalla Mohammed,Suleiman Mohammed Musa,Onukak Charles,Ayo Joseph Olusegun
Asian Pacific Journal of Tropical Biomedicine. 2014; 4(4): 318
[Pubmed] | [DOI]
4 Ameliorative effect of N-acetyl cysteine on alpha-cypermethrin-induced pulmonary toxicity in male rats
Manar Hamed Arafa,Dalia AbdElmoain Mohamed,Hebatallah Husseini Atteia
Environmental Toxicology. 2013; : n/a
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
    Results and Disc...
   Conclusions
   Acknowledgment
    References
    Article Figures

 Article Access Statistics
    Viewed6256    
    Printed185    
    Emailed0    
    PDF Downloaded294    
    Comments [Add]    
    Cited by others 4    

Recommend this journal