Evaluation of Morphological and Mitochondrial Alterations of Mouse Fetus after Exposure to Methyl tert-butyl Ether

Document Type : Research Paper

Authors

1 Dep of Pharmacology and Toxicology, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Valiasr Ave., Tehran, Iran

2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Students Research Committee, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Dept. of Pharmacology and Toxicology, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Valiasr Ave., Tehran, Iran

5 Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran

10.22034/ijps.2018.88396.1446

Abstract

Although the biokinetics, metabolism, and chemical toxicity of methyl tert-butyl ether are well known, little attention was paid to the potential toxic effects of MTBE on reproduction and development in mammals. To evaluate the effects of MTBE on pregnant animals, two groups (control and test) of NMRI mice were chosen. In test group 500 and 1000 mg/Kg of it were administered intraperitonealy at 11 days of gestation and in control group no injection was made. Caesarean section was performed at 15 days of the gestation, and the fetus and placentas were examined externally. Based on our morphological results, MTBE caused significant increase (p < 0.05) in the weight of fetuses and the weight of placentas, the diameter of placentas and crown-rump length of fetuses. Also, our mitochondrial results showed significant (p < 0.05) increase in mitochondrial swelling, ROS formation and also significant (p < 0.05) decreased in MMP on mitochondria isolated from liver and brain in test group. These results suggest that MTBE through ROS formation may induce the mitochondrial dysfunction which in turn leads to inhibition of angiogenesis and morphological alterations in fetus of mouse.

Keywords


[1] Sarhan OM, Jain A, Mutwally HMA, Osman GH, Jung SY, Issa T and Elmogy Mh. Impact effect of methyl tertiary-butyl ether “twelve months vapor inhalation study in rats”. Biology (2020) 9:2-19.
[2] Silva LK, Espenship MF, Pine BN, Ashley DL, De Jesús VR and Blount BC. Methyl tertiary-butyl ether exposure from gasoline in the U.S. population, NHANES 2001–2012. Environ. Health Perspect. (2019) 127: 1-7.
[3] Dodd D, Willson G, Parkinson H and Bermudez E. Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats. J. Appl .Toxicol. (2013) 33: 593-606.
[4] Xiao W, Zhang Y, Wang X, Jiang X, Ma W and He G. Parameters optimization of MTBE reactive distillation process with response surface methodology. Chem. Eng. Trans. (2019) 76:541-546.
[5] Bragadeshwaran A, Kasianantham N, Ballusamy S, Tarun KR, Dharmaraj AP and Kaisan MU. Experimental study of methyl tert-butyl ether as an oxygenated additive in diesel and Calophyllum inophyllum methyl ester blended fuel in CI engine. Environ. Sci. Pollut. Res. (2018) 25:33573-33590.
[6] McGregor, D. Tertiary-butanol: A toxicological review. Crit. Rev. Toxicol. (2010) 40:697-727.
[7] Zhang L, Qin J, Zhang Z, Li Q, Huang J, Peng X, Qing L, Liang G, Liang L, Huang Y, Yang X and Zou Y. Concentrations and potential health risks of methyl tertiary-butyl ether (MTBE) in air and drinking water from Nanning, South China. Sci. Total. Environ. (2016) 541:1348-1354.
[8] Zare K and Naeimi N. Effect of methyl tertiary-butyl on blood parameters and liver tissue in NMRI albino female mice. JMMS. (2017) 27: 49-62.
[9] Badr AA, Saadat I and Saadat M. Study of liver function and expression of some detoxification genes in the male rats exposed to methyl-tertiary butyl ether. Egypt. J. Med. Hum. Genet. (2016) 17:325-329.
[10] Hosseini MJ, Naserzadeh P, Salimi A and Pourahmad J. Toxicity of cigarette smoke on isolated lung, heart, and brain mitochondria: induction of oxidative stress and cytochrome c release. Toxicol. Environ. Chem. (2013) 95:1624-1637.
[11] Salimi A, Roudkenar MH, Seydi E, Sadeghi L, Mohseni A, Pirahmadi N and Pourahmad J. Chrysin as an Anti-Cancer Agent Exerts Selective Toxicity by Directly Inhibiting Mitochondrial Complex II and V in CLL B-lymphocytes. Cancer Invest. (2017) 35:174-186.
[12]Baracca A, Sgarbi G, Solaini G and Lenaz G. Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F0 during ATP synthesis. Biochim. Biophys. Acta. Gen. Subj. (2003) 1606:137–146.
[13] Salimi A, Motallebi A, Ayatollahi M, Seydi E, Mohseni AR, Nazemi M and Pourahmad J. Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting. Environ. Toxicol. (2017) 32:1158-1169.
[14] Baldacci S, Gorini F, Santoro M, Pierini A, Minichilli F and Bianchi F. Environmental and individual exposure and the risk of congenital anomalies: A review of recent epidemiological evidence. Epidemiol Prev. (2018) 42: 1-34.
[15] Rasmussen SA. Human teratogens update 2011: Can we ensure safety during pregnancy?. Birth Defects Res. A. Clin. Mol. Teratol. (2012) 94:123-128.
[16] Kozlosky J, Bonventre J and Cooper K. Methyl tert butyl ether is antiā€angiogenic in both in vitro and in vivo mammalian model systems. J. Appl. Toxicol. (2013) 33:820-827.
[17] Bonventre JA, White LA and Cooper KR. Methyl tert butyl ether targets developing vasculature in zebrafish (Danio rerio) embryos. Aquat. Toxicol. (2011) 105: 29-40.
[18] Conaway CC, Schroeder RE, Snyder NK and Holdsworth C. Teratology evaluation of methyl tertiary butyl ether in rats and mice. J Toxicol. Environ Health A. (1985) 16: 797-809.
[19] Chistiakov, DA, Shkurat TP, Melnichenko AA, Grechko AV and Orekhov AN. The role of mitochondrial dysfunction in cardiovascular disease: a brief review. Ann. Med. (2018) 50:121-127.
[20] Morén C, Hernández S, Guitart-Mampel M and Garrabou G. Mitochondrial toxicity in human pregnancy: an update on clinical and experimental approaches in the last 10 years. Int. J. Environ. Res. Public Health (2014) 11: 9897-9918.
[21] Saeedi A, Omidi M, Khoshnoud MJ and Mohammadi-Bardbori A. Exposure to methyl tertbutyl ether (MTBE) is associated with mitochondrial dysfunction in rat. Xenobiotica (2017) 47:423-430.
[22] Salimi A, Vaghar-Moussavi M, Seydi E and Pourahmad J. Toxicity of methyl tertiary-butyl ether on human blood lymphocytes. Environ. Sci. Pollut .Res. (2016) 23:8556-8564.
[23] Sherer D and Abulafia O. Angiogenesis during implantation, and placental and early embryonic development. Placenta. (2001) 22: 1-13.
[24] Pereira RD, De Long NE, Wang RC, Yazdi FT, Holloway AC and Raha S. Angiogenesis in the placenta: The role of reactive oxygen species signaling. Bio.Med. Res. Int. (2015) 2015: 814543