Chem Biol Interact. 2014 Mar 25;211:11-9.

Exacerbation of intestinal brush border enzyme activities and oxidative stress in streptozotocin-induced diabetic rats by monocrotophos.
 

Vismaya1, Rajini PS2.
  • 1Food Protectants and Infestation Control Department, CSIR-Central Food Technological Research Institute, Mysore 570 020, India.
  • 2Food Protectants and Infestation Control Department, CSIR-Central Food Technological Research Institute, Mysore 570 020, India. Electronic address: rajini29@yahoo.com.

 

Abstract

The present study was undertaken to investigate the potential of monocrotophos (MCP), one of the widely used broad spectrum systemic organophosphorus insecticides (OPI) in India, to alter small intestinal structure and function. Further, its potential to exacerbate diabetes induced alterations in intestinal structure and function was also studied in experimentally induced diabetic rats. Rats were rendered diabetic with an acute dose of streptozotocin (60 mg/kg b.w.). MCP was orally administered at a sublethal dose (1/20 LD50 i.e. 0.9 mg/kg b.w./d) for 15 days to both normal and diabetic rats. MCP significantly increased unit weight of intestine in diabetic rats. MCP alone increased (up to 57%) the activities of intestinal brush border disaccharidases in normal rats and further augmented the enzyme activities in diabetic rats. Similar results were found with intestinal alkaline phosphatase activity. In addition, Na(+)/K(+)-ATPase activity was found to be aggravated in diabetic rats by MCP treatment. Oxidative stress markers showed similar degree of change in both MCP and diabetic rats while MCP aggravated oxidative stress condition in diabetic rats. Scanning electron microscopy and histological analysis of the small intestine revealed increased length of villi, congestion, goblet cell hyperplasia and infiltration of inflammatory cells in MCP and diabetic rats while MCP also induced necrotic lesions in diabetic rats. Collectively, our findings provide evidence that multiple doses of MCP has the propensity to augment diabetes associated intestinal dysfunctions in rats. Copyright © 2014 Elsevier Ireland Ltd.

KEYWORDS: Brush border enzymes; Diabetes; Disaccharidases; Monocrotophos; Small intestine

PMID: 24440807

 

Supplement:

Data obtained from our earlier experiments (1) indicated that single oral of Monocrotophos (MCP) did not cause any change in the activity of intestinal disaccharidases whereas, repeated doses of MCP enhanced the activities all brush border enzymes in all the regions of small intestine and caused altered redox status. In addition, histological changes and ultra-structural alterations in villi were noticed in the intestinal regions. Further, MCP treatment for 15 days augmented the biochemical and structural alterations significantly in the jejunum portion of the small intestine of diabetic rats. So, we were interested in exploring the long term impact of MCP on the small intestine of experimentally induced diabetes. Hence, a study was planned to examine the impact of repeated oral doses (30d) of MCP in experimentally induced diabetic rats in terms of effect on brush border enzymes, oxidative stress parameters and ultra structure of small intestine.

Interestingly we found that in 30d treatment with MCP significantly increased the activities of all the four disaccharidases (maltase, sucrase, lactase and trehalase) in all the treatment groups. In addition to increased activity in jejunum part (as observed in 15d experiment), enhanced disaccahridase activity was observed in STZ+MCP group in duodenum and ileum also. Scanning electron microscopic observation revealed significant alterations in all the three intestinal regions – duodenum, jejunum and ileum.

Collectively, our study provides evidence for the potential of MCP to augment dysfunctions in the small intestine of diabetic rats. Besides affecting glucose homeostasis as reported earlier from our laboratory (2), the current work establishes the fact that long-term exposure to MCP residues may interfere with the digestive capacity of the small intestine by altering the brush border enzymes and the structure of the small intestine, which might also contribute towards postprandial hyperglycemia. Further, our results clearly demonstrate that the intestine of diabetic rats are prone to further structural, functional and oxidative damage by MCP on chronic exposure, which might result in exacerbated intestinal dysfunction.

References

  1. Vismaya and Rajini P.S . Oral exposure to the organophosphorus insecticide, Monocrotophos induces intestinal dysfunction in rats. Food and Chemical Toxicology 71 (2014) 236–243.
  2. Apurva Kumar R. Joshi and P.S. Rajini. Organophosphorus Insecticides and Glucose Homeostasis, Source: Insecticides – Pest Engineering, ISBN 978-953-307-895-3, Edited by: Farzana Perveen; Publisher: InTech, February 2012. (http://www.intechopen.com/articles/show/title/organophosphorus-insecticides-and-glucose-homeostasis).
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