Effect of early natal supplementation of paracetamol on attenuation of exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in albino rats

Abstract

The present study was aimed to test the hypothesis that paracetamol (PCM) can precipitate autistic like features when used to counteract vaccine-induced fever using experimental rat pups. The pups were treated with measles mumps rubella (MMR) vaccine, diphtheria tetanus and pertussis (DPT) vaccines and lipopolysaccharide (LPS) with subsequent PCM treatment. The pups were evaluated for postnatal growth (weight gain, eye opening) and behavior alterations (swimming performance, olfactory discrimination, negative geotaxis, nociception, and locomotor activity) by performing battery of neurobehavioral test. Significant correlation was observed between social behavioral domains (nociception, anxiety and motor coordination) and pro-inflammatory load in the pups when treated with MMR/LPS along with PCM. A significant change in pro and anti-inflammatory (IL-4, IL-6, IL-10) markers were observed in rats treated with PCM, MMR, LPS, DPS alone or in combination with MMR, LPS and DPT (5128.6 ± 0.000, 15,488 ± 0.000***, 9661.1 ± 157.29***a, 15,312 ± 249.29***, 10,471 ± 0.00***a, 16,789 ± 273.34*** and 12,882 ± 0.00***a). Pups were also scrutinized for the markers of oxidative stress, inflammation and histopathologically. All the treatment groups showed significant alteration in the behavioral changes, oxidative markers (TBARS-in control-4.33 ± 0.02, PCM-9.42 ± 0.18***, MMR-5.27 ± 0.15***, MMR + PCM-8.57 ± 0.18*** a, LPS-6.84 ± 0.10***, LPS + PCM-4.51 ± 0.30***a, DPT-5.68 ± 0.12***, DPT + PCM-7.26 ± 0.18***a) and inflammatory markers without following any specific treatment. These observation could be accorded to variable phenotypes of autistic spectrum disorders (ASDs).

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References

  1. Aggarwal B, Prasad BS et al (2011) Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: “reverse pharmacology” and “bedside to bench” approach. Curr Drug Targets 12(11):1595–1653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Ahmad A, Kumar V et al (2013) Natural antiulcer agents: a pharmacological review. Int J Res Pharm Biomed Sci 4:535–541

    Google Scholar 

  3. Alqasoumi S, Al-Dosari M et al (2011) Gastric antiulcer activity of a pungent spice Ferula assafoetida in rats. Farmacia 59:750–759

    Google Scholar 

  4. Amr R, Maysa E (2010) Antiulcer effect of cinnamon and chamomile aqueous extracts in rats models. J Am Sci 6:209–216

    Google Scholar 

  5. Andrade C (2016) Use of acetaminophen (paracetamol) during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring. J Clin Psychiatry 77(3):e312–e314

    Article  PubMed  Google Scholar 

  6. Barker V, Middleton G, Davey F, Davies AM (2001) TNFα contributes to the death of NGF-dependent neurons during development. Nat Neurosci 4(12):1194–1198

  7. Borrelli F, Izzo AA (2000) The plant kingdom as a source of anti-ulcer remedies. Phytother Res 14(8):581–591

    Article  PubMed  CAS  Google Scholar 

  8. Brunton LL, Chabner B et al (2011) Goodman and Gilman’s the pharmacological basis of therapeutics. McGraw-Hill Medical, New York

    Google Scholar 

  9. Ding Y, Zhou Y et al (2012) Laparoscopic management of perforated Meckel’s diverticulum in adults. Int J Med Sci 9(3):243–247

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dorsinville J-M (2015) Celebrating Our Prince: DIMITRI The Face of ADHD. 1–290

  11. Falcão H, Mariath I et al (2008) Plants of the American continent with antiulcer activity. Phytomedicine 15(1):132–146

    Article  PubMed  Google Scholar 

  12. Gadekar R, Singour P et al (2010) A potential of some medicinal plants as an antiulcer agents. Pharmacogn Rev 4(8):136

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Ghanizadeh A (2012) Acetaminophen may mediate oxidative stress and neurotoxicity in autism. Med Hypotheses 78(2):351

    Article  PubMed  CAS  Google Scholar 

  14. Gilmore JH, Jarskog LF, Vadlamudi S (2005) Maternal poly I:C exposure during pregnancy regulates TNF alpha, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat. J Neuroimmunol 159:106–112

  15. Gregory M, Vithalrao K et al (2009) Anti-ulcer (ulcer-preventive) activity of Ficus arnottiana Miq.(Moraceae) leaf methanolic extract

  16. Gupta M, Shaw B (2009) Uses of medicinal plants in Panchakarma Ayurvedic therapy. Indian J Tradit Knowl 8:372–378

    Google Scholar 

  17. Howland RD, Mycek MJ et al (2006) Lippincott’s illustrated reviews: pharmacology. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  18. Jain D, Baheti A et al (2010) Use of medicinal plants among tribes in Satpuda region of Dhule and Jalgaon districts of Maharashtra—an ethnobotanical survey. Indian J Tradit Knowl 9(1):152–157

    Google Scholar 

  19. Kamble S, Patil S et al (2010) Studies on plants used in traditional medicine by Bhilla tribe of Maharashtra. Indian J Tradit Knowl 9(3):591–598

    Google Scholar 

  20. Karuppusamy S, Pullaiah T (2009) Pollination systems and ex situ fruit set in Ceropegia juncea Wight (Apocynaceae)—an endemic species in India. Acad J Plant Sci 2:242–245

    Google Scholar 

  21. Kosif R, Akta G et al (2008) Microscopic examination of placenta of rats prenatally exposed to Aloe barbadensis: a preliminary study. Int J Morphol 26(2):275–281

    Article  Google Scholar 

  22. Kota BP, Teoh AW et al (2012) Pharmacology of traditional herbal medicines and their active principles used in the treatment of peptic ulcer, diarrhoea and inflammatory bowel disease, INTECH Open Access Publisher

  23. Kumar R, Bhagat N (2012) Ethnomedicinal plants of district Kathua (J&K). Int J Med Aromat Plants 2(4):603–611

    Google Scholar 

  24. Kumar M, Paul Y et al (2009) An ethnobotanical study of medicinal plants used by the locals in Kishtwar, Jammu and Kashmir, India. Ethnobot Leafl 2009(10):5

    Article  Google Scholar 

  25. Kumar R, Niyas M et al (2011) A review on medicinal plants for peptic ulcer. Der Pharmacia Lettre 3(3):414–420

    Google Scholar 

  26. Maury PK, Jain S et al (2012) A review on antiulcer activity. Int J Pharm Sci Res 3(8):2487

    Google Scholar 

  27. Minaiyan M, Ghannadi A et al (2012) A study of the effects of Cydonia oblonga Miller (Quince) on TNBS-induced ulcerative colitis in rats. Res Pharm Sci 7(2):103–110

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Nigam V, Paarakh PM (2011) Anti-ulcer effect of Chenopodium album Linn. against gastric ulcers in rats. Int J Pharm Sci Drug Res 3(4):319–322

    Google Scholar 

  29. Nikhat S, Khan JA et al (2012) Some experimentally proved herbs in peptic ulcer disease. Int J Pharm Sci Res 3(8):2387

    Google Scholar 

  30. Patankar R, Devale T et al (2011) Antiulcer activity of acacia catechu wild in rats. Int J Res Ayurveda Pharm 2(5):1585–1587

  31. Priya CL, Rao KVB (2012) Ethanobotanical and current ethanopharmacological aspects of Argemone mexicana Linn: an overview. Int J Pharm Sci Res 3(7):2143

    Google Scholar 

  32. Purohit M, Shanthaveerappa B et al (2013) Antiulcer and anticatatonic activity of alcoholic extract of Evolvulus alsinoides (convolvulaceae). Ind J Pharma Sci 58(3):110–112

  33. Rafatullah S, Al-Yahya M et al (1994) Gastric anti-ulcer and cytoprotective effects of Cyamopsis tetragonoloba (‘Guar’) in rats. Int J Pharmacogn 32(2):163–170

    Article  Google Scholar 

  34. Raja AE, Vijayalakshmi M et al (2009) Acorus calamus Linn.: chemistry and biology. Res J Pharm Technol 2(2):256–261

    CAS  Google Scholar 

  35. Ramasubramaniaraja R, Niranjan Babu M (2011) Peptic ulcer and phytochemistry: an overview. J Pharm Res 4(1):156–160

    CAS  Google Scholar 

  36. Sakat S, Tupe P et al (2012) Gastroprotective effect of Oxalis corniculata (whole plant) on experimentally induced gastric ulceration in Wistar rats. Indian J Pharm Sci 74(1):48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Saurabh A, Mishra AS et al (2012) A review on medicinal plant, which may effective in the treatment of ulcer or which show antiulcer activities. Int J Biopharm Toxicol Res 2(1):266–276

    Google Scholar 

  38. Schultz ST (2010) Can autism be triggered by acetaminophen activation of the endocannabinoid system? Acta Neurobiol Exp 70(2):227–231

    Google Scholar 

  39. Sharma N, Gautam S et al (2015) Preclinical appraisal of terbutaline analogues in precipitation of autism spectrum disorder. RSC Adv 5(49):39003–39011

    Article  CAS  Google Scholar 

  40. Thirunavukkarasu P, Ramkumar L et al (2009) Anti-ulcer activity of Excoecaria agallocha bark on NSAID-induced gastric ulcer in Albino rats. Glob J Pharmacol 3(3):123–126

    Google Scholar 

  41. Thirunavukkarasu P, Ramanathan T et al (2010) Anti ulcer effect of Avicennia officinalis leaves in Albino rats. World Appl Sci J 9(1):55–58

    CAS  Google Scholar 

  42. Tripathi K (2008) Essential of medical pharmacology. Jaypee brothers medical publishers (P) LTD, Dhaka, pp 769–775

    Google Scholar 

  43. Umashanker M, Shruti S (2011) Traditional Indian herbal medicine used as antipyretic, antiulcer, anti-diabetic and anticancer: a review. Int J Res Pharm Chem 1(4):1152–1159

    Google Scholar 

  44. Venkatalakshmi P, Senthamaraiselvi V (2012) Anti ulcer effect of basella alba leaf extract in aspirin induced albino rats. Int J Pharm Sci Res 3(8):2539

    Google Scholar 

  45. Venkataswamy R, Mubarack HM et al (2010) Ethnobotanical study of medicinal plants used by Malasar tribals in Coimbatore District of Tamil Nadu (South India). Asian J Exp Biol Sci 1(2):387–392

    Google Scholar 

  46. Verma M (2010) Investigation on antiulcer activity of Aegle marmelos root as experimental, biochemical and histological study. J Pharm Res 3(10):2523–2528

    CAS  Google Scholar 

  47. Vinothapooshan G, Sundar K (2010) Anti-ulcer activity of Mimosa pudica leaves against gastric ulcer in rats. Res J Pharm Biol Chem Sci 1(4):606–614

    Google Scholar 

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Acknowledgements

Author would like to acknowledge the UGC for granting the fellowship to IS, MS, JKR, SG, SD, and RKY.

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ASS, IS: Performed the animal experimentation, SG, MS, JKR, UD: Performed the biochemical parameters and histopathology, RKY: Statistical analysis, MNA: Final draft of revised manuscript, GK: Perceived the idea of study, final proof reading of manuscript.

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Correspondence to Gaurav Kaithwas.

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Saeedan, A.S., Singh, I., Ansari, M.N. et al. Effect of early natal supplementation of paracetamol on attenuation of exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in albino rats. Inflammopharmacol 26, 951–961 (2018). https://doi.org/10.1007/s10787-017-0440-2

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Keywords

  • Autism
  • Lipopolysaccharide
  • Cyclooxygenase
  • Interleukin
  • Lipoxygenase
  • Paracetamol