Potential effect of fish oil to preserve expression of cell cycle and tight junction regulating genes in colon after di-isononyl phthalate ingestion in albino Wistar rats


Di-isononyl phthalate (DIP) is considered a high molecular-weight subtype of phthalates that are commonly used and could easily affect the gastrointestinal tract (GIT). Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the main active components of fish oil (FO), and their anti-inflammatory potential was previously documented. The current study was designed to investigate the protective potential of fish oil against the impacts of DIP exposure on the colon of albino Wistar rats. Sixty albino Wistar rats were divided into Control group received corn oil for ten days. Di-isononyl phthalate treated group received DIP. Di-isononyl phthalate + fish oil treated group received both DIP and FO. FO was found to preserve the histological architecture, tight junction and cell cycle of the colon. In conclusion, the current study provided an evidence that FO has a protective potential against DIP further examinations to be done to fully understand the molecular basis of this potential as a step for further clinical applications.



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Zhang H, Hua Y, Chen J, Li X, Bai X, Wang H. Organism-derived phthalate derivatives as bioactive natural products. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2018;36:125-44.

Bølling AK, Sripada K, Becher R, Bekö G. Phthalate exposure and allergic diseases: Review of epidemiological and experimental evidence. Environ Int 2020;139:105706.

Chiu K, Bashir ST, Nowak RA, Mei W, Flaws JA. Subacute exposure to di-isononyl phthalate alters the morphology, endocrine function, and immune system in the colon of adult female mice. Sci Rep 2020;10:18788.

Forner-Piquer I, Maradonna F, Gioacchini G, Santangeli S, Allarà M, Piscitelli F, et al. Dose-specific effects of Di-isononyl phthalate on the endocannabinoid system and on liver of female zebrafish. Endocrinology 2017;158:3462-76.

Tummala R, Ghosh RK, Jain V, Devanabanda AR, Bandyopadhyay D, Deedwania P, Aronow WS. Fish oil and cardiometabolic diseases: recent updates and controversies. Am J Med 2019;132:1153-9.

Harris WS. Understanding why REDUCE-IT was positive - Mechanistic overview of eicosapentaenoic acid. Prog Cardiovasc Dis 2019;62:401-5.

Trivedi K, Le V, Nelson JR. The case for adding eicosapentaenoic acid (icosapent ethyl) to the ABCs of cardiovascular disease prevention. Postgrad Med 2021;133:28-41.

Ma P, Yan B, Zeng Q, Liu X, Wu Y, Jiao M, et al. Oral exposure of Kunming mice to diisononyl phthalate induces hepatic and renal tissue injury through the accumulation of ROS. Protective effect of melatonin. Food Chem Toxicol 2014;68:247-56.

Albert BB, Vickers MH, Gray C, Reynolds CM, Segovia SA, Derraik JGB, et al. Fish oil supplementation to rats fed high-fat diet during pregnancy prevents development of impaired insulin sensitivity in male adult offspring. Sci Rep 2017;7:5595.

Laferriere CA, Pang DS. Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. J Am Assoc Lab Anim Sci 2020;59:254-63.

Slaoui M, Fiette L. Histopathology procedures: from tissue sampling to histopathological evaluation. Methods Mol Biol 2011;691:69-82.

Winston B, Nalesnik M, Bazaz R. TUNEL assay for identifying ablated myocardium. Pacing Clin Electrophysiol 2010;33:1548-9.

Singh C, Roy-Chowdhuri S. Quantitative Real-Time PCR: Recent advances. Methods Mol Biol 2016;1392:161-76.

Ahmed AS. Potential protective effect of eicosapentaenoic and docosahexaenoic acids versus necrotizing enterocolitis, mitochondrial and rough endoplasmic reticulum stress mediated pathway. Eur J Anat 2021;25:65-73.

Yu J, Wang W, Wang J, Wang C, Li C. Short-term toxicity of dibutyl phthalate to mice intestinal tissue. Toxicol Ind Health 2019;35:20-31.

Sadeghi N, Paknezhad F, Rashidi Nooshabadi M, Kavianpour M, Jafari Rad S, Khadem Haghighian H. Vitamin E and fish oil, separately or in combination, on treatment of primary dysmenorrhea: a double-blind, randomized clinical trial. Gynecol Endocrinol 2018;34:804-8.

Park CJ, Kim H, Jin J, Barakat R, Lin PC, Choi JM, Ko CJ. Porcine intestinal lymphoid tissues synthesize estradiol. J Vet Sci 2018;19:477-82.

Long SE, Kahn LG, Trasande L, Jacobson MH. Urinary phthalate metabolites and alternatives and serum sex steroid hormones among pre- and postmenopausal women from NHANES, 2013-16. Sci Total Environ 2021;769:144560.

Ma Q. MiR-219-5p suppresses cell proliferation and cell cycle progression in esophageal squamous cell carcinoma by targeting CCNA2. Cell Mol Biol Lett 2019;24:4.

Meling DD, Warner GR, Szumski JR, Gao L, Gonsioroski AV, Rattan S, Flaws JA. The effects of a phthalate metabolite mixture on antral follicle growth and sex steroid synthesis in mice. Toxicol Appl Pharmacol 2020;388:114875.

Dos Santos TM, Righetti RF, Camargo LDN, Saraiva-Romanholo BM, Aristoteles LRCRB, de Souza FCR, et al. Effect of Anti-IL17 antibody treatment alone and in combination with rho-kinase inhibitor in a murine model of asthma. Front Physiol 2018;9:1183.

Furue K, Ito T, Tsuji G, Ulzii D, Vu YH, Kido-Nakahara M, Nakahara T, Furue M. The IL-13-OVOL1-FLG axis in atopic dermatitis. Immunology 2019;158:281-6.

Jost PJ, Vucic D. Regulation of cell death and immunity by XIAP. Cold Spring Harb Perspect Biol 2020;12:a036426.

Al-Sadi R, Boivin M, Ma T. Mechanism of cytokine modulation of epithelial tight junction barrier. Front Biosci (Landmark Ed) 2009;14:2765-78.

Murphy EF, Jewell C, Hooiveld GJ, Muller M, Cashman KD. Conjugated linoleic acid enhances transepithelial calcium transport in human intestinal-like Caco-2 cells: an insight into molecular changes. Prostaglandins Leukot Essent Fatty Acids 2006;74:295-301.

Siti Sarah CO, Md Shukri N, Mohd Ashari NS, Wong KK. Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis. PeerJ 2020;8:e9834.

Chien YW, Peng HC, Chen YL, Pai MH, Wang HY, Chuang HL, Yang SC. Different dietary proportions of fish oil regulate inflammatory factors but do not change intestinal tight junction ZO-1 expression in ethanol-fed rats. Mediators Inflamm 2017;2017:5801768.

Di-isononyl phthalate, gastrointestinal tract, fish oil, tight junction, apoptosis
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Ahmed, A. S., Ibrahim, H. A., & Hantash , E. M. (2021). Potential effect of fish oil to preserve expression of cell cycle and tight junction regulating genes in colon after di-isononyl phthalate ingestion in albino Wistar rats. European Journal of Histochemistry, 65(2). https://doi.org/10.4081/ejh.2021.3232