International Journal of Drug Delivery Technology
Volume 14, Issue 2

In-vivo Toxicity Profile of 2-Butyl-3-(3, 5-Diiodo-4-Hydroxybenzoyl) Benzofuran on Different Experimental Models

Sowjanya Akula1*, Gubbiya Shiva Kumar 2

1Department of Pharmacology, GITAM School of Pharmacy (GITAM Deemed to be University), Hyderabad, Telangana, India.

2Department of Pharmacognosy, GITAM School of Pharmacy (GITAM Deemed to be University), Rudraram, Hyderabad, Telangana, India. 

Received: 23nd November, 2023; Revised: 16th January, 2024; Accepted: 16th April, 2024; Available Online: 25th June, 2024 

ABSTRACT

The anti-cancer properties of 2-butyl-3-(3, 5-Diiodo-4-Hydroxybenzoyl) benzofuran have been determined in earlier in-vitro studies, but safety and efficacy still need to be resolved. This research investigates the acute oral toxicity of 2-butyl-3-(3, 5-diiodo-4-hydroxybenzoyl) benzofuran on female Wistar rats, zebrafish, and brine shrimp. The present study was conducted on rats to evaluate the compound acute oral toxicity, following the protocols established by the Organization for Economic Cooperation and Development (OECD) 423. After 14 days of duration, histopathological changes were observed in the liver and heart of animals that received a dosage of 2,000 mg/kg. The compound was tested at a limit test concentration of 100 mg/L in zebrafish for period of 96 hours. During this time, sub-lethal clinical signs and mortalities were observed at 24, 48, 72, and 96 hours. Brine shrimps were exposed to various concentrations for 24 hours to evaluate their cytotoxicity and calculate the percentage of mortality. Histopathological changes are primarily observed in the liver (multifocal necrosis of hepatocytes), heart (myocardial inflammation) and lung (low alveolar/interstitial inflammation). There are no recordings of mortalities at 300 and 2,000 mg/kg treated rats. Behavioral patterns remained unchanged, whereas food intake and body weight decreased significantly. The oral administration of the test chemical to rats would result in an LD50 greater than 2,000 mg/kg, ranking it in the fifth category of the GHS. The LC50 (322.96 µg/mL) for the brine shrimp lethality assay was calculated using a plotted graph. The test compound’s LC50 value in the zebrafish model would be higher than 100 mg/L. The acute toxicity profile of 2-butyl-3-(3, 5-diiodo-4-hydroxybenzoyl) benzofuran has been demonstrated using rodents, zebrafish, and brine shrimp lethality assay. This study will guide subsequent chronic toxicological assessments.

Keywords: Acute toxicity, Brine shrimp, Rats, OECD, Zebrafish

International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.2.49

How to cite this article: Akula S, Kumar GS. In-vivo Txicity Profile of 2-Butyl-3-(3, 5-Diiodo-4-Hydroxybenzoyl) Benzofuran on Different Experimental Models. International Journal of Drug Delivery Technology. 2024;14(2):932-937.

REFERENCES

  1. Gad SC. Alternatives to In‐Vivo Studies in Toxicology. Mammalian 2015 Feb 27:15- 47.10.1002/9781118683484.ch2
  2. Saoudi, M., Taher, I. Comparative Study of Several Extraction Solvents on Phenolic Profile, Toxicity and Antioxidants Potential of Ephedra alata Advanced Journal of Chemistry-Section B: Natural Products and Medical Chemistry, 4(4): 239-246, 2022; doi: 10.22034/ajcb.2022.366558.1128
  3. Erhirhie EO, Ihekwereme CP, Ilodigwe Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance. Interdisciplinary toxicology. May 1;11(1):5-12, 2018 DOI: https://doi.org/10.2478/intox-2018-0001.
  4. Sowjanya A, Kumar In-silico and In-vitro Studies on Targeting Tumor Apoptosis by Activating Caspase-3. International Journal of Pharmaceutical Quality Assurance. 2023;14(3):661-670; DOI:10.25258/ijpqa.14.3.34.
  5. Walum Acute oral toxicity. Environmental health perspectives. Apr;106(suppl 2):497-503, 1998 https://doi.org/10.1289
  6. Ukwubile, C., Ikpefan, E., Bingari, M., Tam, L. Acute and subchronic toxicity profiles of Melastomastrum capitatum (Vahl) (Melastomataceae) root aqueous extract in Swiss albino mice. Progress in Chemical and Biochemical Research,2(2): 74-83, 2019 DOI: 10.33945/SAMI/pcbr.2019.92077
  7. Paparella M, Scholz S, Belanger S, Braunbeck T, Bicherel P, Connors K, Faßbender C, Halder M, Lillicrap A, Liska R, Schirmer K. Limitations and uncertainties of acute fish toxicity assessments can be reduced using alternative methods. 38(1):20-32.2021, https://doi.org/10.14573/altex.2006051.
  8. Rubinstein AL. Zebrafish assays for drug toxicity screening. Expert opinion on drug metabolism and toxicology. Apr 1;2(2):231-40, 2006, https://doi.org/10.1517/17425255.2.2.231
  9. Choi TY, Choi TI, Lee YR, Choe SK, Kim CH. Zebrafish as an animal model for biomedical research. Experimental and Molecular Medicine. 2021 Mar;53(3):310-7, DOI: 1038/ s12276-021-00571-5
  10. Sarah QS, Anny FC, Misbahuddin M. Brine shrimp lethality assay. Bangladesh Journal of 2017, Jun 5;12(2):186-9. DOI:10.3329/bjp.v12i2.32796
  11. Vidotto C, da Silva DB, Patussi R, Brandão LF, Tiburcio JD, Alves SN, de Siqueira JM. Brine shrimp lethality test as a biological model for preliminary selection of pediculicidal components from natural source. Bioscience Journal. 2013, 29(1):255- 63, DOI:10.13140/2.1.4422.5929
  12. OECD GUIDELINE FOR TESTING OF CHEMICALS, Acute Oral Toxicity –acute toxic class method
  13. Adedayo AD, Tijani AA, Musa AA, Adeniyi TD. Histological study of smoke extract of Tobacco nicotiana on the heart, liver, lungs, kidney, and testes of male Sprague-Dawley Nigerian medical journal: journal of the Nigeria Medical Association. Oct;52(4):217, 2011, DOI: 10.4103/0300-1652.93791.
  14. OECD Guidelines for the Testing of Chemicals, Test No. 203: Fish, Acute Toxicity Test.
  15. Waghulde S, Kale MK, Patil Brine shrimp lethality assay of the aqueous and ethanolic extracts of the selected species of medicinal plants. InProceedings 2019 Nov 19 (Vol. 41, No. 1, p. 47). MDPI.The 23rd International Electronic Conference on Synthetic Organic Chemistry, DOI:10.3390/ecsoc-23-06703.
  16. Ntungwe N E, Domínguez-Martín EM, Roberto A, Tavares J, Isca V, Pereira P, Cebola MJ, Rijo P. Artemia species: An important tool to screen general toxicity Current Pharmaceutical Design. Jul 1;26(24):2892-908, 2020 DOI: 10.2 174/1381612826666200406083035
  17. Schlede E, Mischke U, Diener W, Kayser D. The international validation study of the acute toxic class method (oral). Archives of toxicology.1995, Oct;69:659-70, DOI: 10.1007/s002040050229
  18. Cassar S, Adatto I, Freeman JL, Gamse JT, Iturria I, Lawrence C, Muriana A, Peterson RT, Van Cruchten S, Zon LI. Use of zebrafish in drug discovery Chemical research in toxicology, 2019, Oct 18;33(1):95-118, doi: 10.1021/acs. chemrestox.9b00335
  19. Burden N, Benstead R, Benyon K, Clook M, Green C, Handley J, Harper N, Maynard SK, Mead C, Pearson A, Ryder K. Key opportunities to replace, reduce, and refine regulatory fish acute toxicity tests. Environmental Toxicology and Chemistry. 2020 Oct;39(10):2076-89, https://doi.org/10.1002/etc.4824
  20. Ramachandran S, Vamsikrishna M, Gowthami KV, Heera B, Dhanaraju MD. Assessment of cytotoxic activity of Agave cantula using brine shrimp (Artemia salina) lethality bioassay. AsianJ Sci Res. 2011;4(1):90-4, DOI: 3923/ajsr.2011.90.94
  21. Rajeshkumar S, Subramanian AK, Prabhakar R. Invitro anti- inflammatory activity of silymarin/hydroxyapatite/chitosan nanocomposites and its cytotoxic effect using brine shrimp lethality assay: nanocomposite for biomedical applications. Journal of Population Therapeutics and Clinical Pharmacology. 28(2), 2021 DOI https://doi.org/10.47750/jptcp.2022.874