Wistar Sıçanlarında Tinerin Neden Olduğu Çoklu Organ Toksisiteleri: E Vitamininin (Alfa-Tokoferol) İyileştirici Rolü

Abstract

Yaygın bir endüstriyel çözücü olan tiner, keyfi amaçlı kendi kendine zehirlenme için yaygın bir seçimdir ve potansiyel ciddi sağlık sonuçlarına yol açmaktadır. Bu çalışma, tinerin akut toksisitesini, çeşitli organ sistemleri üzerindeki etkisine ve bir antioksidan olarak E Vitamininin potansiyel iyileştirici yeteneğine odaklanarak incelemektedir. Wistar sıçanlardan oluşan dört deney grubu (n-12) şu şekilde oluşturulmuştur: kontrol, sadece E Vitamini, sadece tiner ve tiner + E Vitamini. Sıçanlar 3 haftalık bir inhalasyon protokolüne tabi tutulmuş ve vücut ağırlığı, biyokimyasal belirteçler (aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), alkalin fosfataz (ALP), total bilirubin (TBIL) gibi çeşitli parametreler ölçülmüştür, kan üre azotu (BUN) ve kreatinin seviyeleri), oksidatif stres belirteçleri (malondialdehit, nitritler, glutatyon, katalaz ve süperoksit dismutaz) ve histopatolojik incelemeler standart prosedürler kullanılarak değerlendirilmiştir. Sonuçlar, tiner maruz kalan grupta vücut ağırlığında önemli bir azalma olduğunu ortaya koymuştur. Bununla birlikte, hem tiner hem de E Vitaminine maruz kalan grupta vücut ağırlığında belirgin bir artış görülmüştür. Biyokimyasal parametreler (AST, ALT, ALP, TBIL, BUN ve kreatinin) sadece tinere maruz kalan sıçanlarda önemli ölçüde yükselmiştir (p<0,05). Tersine, tiner ve E vitamini birlikte uygulanan sıçanlarda parametreler belirgin şekilde azalmıştır. Farklı doku oksidatif stres belirteç profilleri sadece tinerle tedavi edilen sıçanlarda önemli ölçüde değişmiştir. İlginç bir şekilde, E vitamini takviyesi belirteçlerdeki değişiklikleri önemli ölçüde tersine çevirmiştir. Tiner maruziyeti karaciğer, böbrekler, akciğerler ve dalakta ciddi histomorfolojik bozulmalara yol açmıştır. Dikkat çekici bir şekilde, E vitamininin tiner ile birlikte uygulanması organlardaki yapısal hasarı belirgin bir şekilde iyileştirmiştir. Bu çalışma, tiner kaynaklı toksisitenin olumsuz etkilerini hafifletmede E Vitamininin potansiyel terapötik rolünü vurgulamakta ve solvent kullanımına bağlı sağlık komplikasyonlarının yönetiminde antioksidan bir strateji olarak önemini ortaya koymaktadır.

Keywords

• İnceltici
• toksisite
• E vitamini
• antioksidan
• histopatoloji

Thinner Induced Multiple Organ Toxicities in Wistar Rats: Ameliorative Role of Vitamin E (Alpha-Tocopherol)

Abstract

Thinner, a common industrial solvent, is a popular choice for recreational self-intoxication, leading to potential serious health consequences. This study delves into the acute toxicity of thinner, focusing on its impact on various organ systems and the potential ameliorative ability of Vitamin E as an antioxidant. Four experimental groups of Wistar rats (n-12) were established as follow: control, Vitamin E only, thinner only and thinner + Vitamin E. The rats were subjected to a 3week inhalation protocol, and various parameters such as body weight, biochemical markers (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), blood urea nitrogen (BUN) and creatinine levels), oxidative stress markers (malondialdehyde, nitrites, glutathione, catalase and superoxide dismutase), and histopathological examinations were assessed using standard procedures. The results revealed a significant reduction in body weight in the thinner-exposed group. However, the group exposed to both thinner and Vitamin E exhibited marked increase in body weight. Biochemical parameters (AST, ALT, ALP, TBIL, BUN and creatinine) were significantly elevated (p<0.05) in thinner only exposed rats. Conversely, the parameters were markedly reduced in the rats co-administered with thinner and vitamin E. The different tissue oxidative stress marker profiles were significantly altered in the thinner only treated rats. Interestingly, vitamin E supplementation significantly reversed the alterations to the markers. Thinner exposure precipitated severe histomorphological disruptions in the liver, kidneys, lungs and spleen. Remarkably, vitamin E co-administration with thinner markedly ameliorate the structural damage to the organs. This study emphasizes the potential therapeutic role of Vitamin E in mitigating the adverse effects of thinner-induced toxicity, suggesting its importance as an antioxidant strategy in managing solvent abuse-related health complications.

Keywords

• Thinner
• toxicity
• vitamin E
• antioxidant
• histopathology

References

1. McGarvey EL, Clavet GJ, Mason W, Waite D. Adolescent inhalant abuse: environments of use. AJDAA 1999; 25(4): 731–741.
2. Jayanth S, Hugar BS, Praveen S, Girish Chandra Y. Glue sniffing. Med Leg J 2016; 85(1): 38-42.
3. Patrick ME, Collins LM, Smith E, Caldwell L, Flisher A, Wegner L. A prospective longitudinal model of substance use onset among South African adolescents. Subst. Use & Misuse 2009; 44(5): 647–662.
4. Young SJ, Longstaffe S, Tenenbein M. Inhalant abuse and the abuse of other drugs. AJDAA 1999; 25(2): 371–375.
5. Howard MO, Bowen SE, Garland EL, Perron BE, Vaughn MG. Inhalant use and inhalant use disorders in the United States. Addict Sci & Clin Pract 2011; 6(1): 18–31.
6. Sato H, Bottle SE, Blinco JP, Micallef AS, Eaton GR, Eaton SS. Electron spin-lattice relaxation of nitroxyl radicals in temperature ranges that span glassy solutions to low viscosity liquids. J Magn Reson 2008;191: 66–77.
7. Martínez-Alfaro M, Alcaraz-Contreras Y, Cárabez-Trejo A, Leo-Amador, GE. Oxidative stress effects of thinner inhalation. Indian J. Occup and Environ Med 2011; 15(3): 87–92.
8. Cruz SL, Armenta-Reséndiz M, Carranza-Aguilar CJ, Galván EJ. Minocycline prevents neuronal hyperexcitability and neuroinflammation in medial prefrontal cortex, as well as memory impairment caused by repeated toluene inhalation in adolescent rats. Toxicol and Appl Pharmacol 2020; 395: 114980.

9. Bennett ME, Walters ST, Miller JH, Woodall WG. Relationship of early inhalant use to substance use in college students. J Subst Abuse 2000; 12(3): 227–240.
10. Crossin R, Qama A, Andrews ZB, Lawrence AJ, Duncan JR. The effect of adolescent inhalant abuse on energy balance and growth. Pharmacol. Res. & Perspect 2019;7(4): e00498.
11. Schikler KN, Seitz K, Rice JF, Strader T. Solvent abuse associated cortical atrophy. J. Adolesc. Health Care: Official Publication of the Society for Adolescent Medicine 1982; 3(1): 37-39.
12. Camara-Lemarroy CR, Rodríguez-Gutiérrez R, Monreal-Robles R, González-González JG. Acute toluene intoxication--clinical presentation, management and prognosis: a prospective observational study. BMC Emerg. Med 2015; 15: 19.
13. Taher SM, Anderson RJ, McCartney R, Popovtzer MM, Schrier RW. Renal tubular acidosis associated with toluene “sniffing”. N Engl J Med 1974; 290(14): 765-768.
14. Kaneko T, Koizumi T, Takezaki T, Sato A. Urinary calculi associated with solvent abuse. Urol J 1992;147(5): 1365–1366.
15. Dündarz MR, Türkbay T, Akay C, Sarici SU, Aydin A, Denli M, Gökçay E. Antioxidant enzymes and lipid peroxidation in adolescents with inhalant abuse. Turk J Pediatr 2003;45(1): 43–45.
16. Yurtseven A, Türksoylu M, Yazıcı P, Karapınar B, Saz EU. A `glue sniffer` teenager with anuric renal failure and hepatitis. Turk J Pediatr 2018; 60(2): 206–209.
17. Arslan Ş, Uzunhasan I, Kocas BB, Cetinkal G, Arslan Ş, Kocas C., Abaci O, Yildiz M, Celiker C, Turkoglu C. Effect of chronic toluene exposure on heart rhythm parameters. Pacing Clin Electrophysiol 2018; 41(7): 783-787.
18. Snyder R. Benzene and leukemia. Crit. Rev in Toxicol 2002;32(3): 155–210.
19. Win-Shwe TT, Fujimaki H. Neurotoxicity of toluene. Toxicol. Lett. 2012; 198(2): 93-99.
20. Backes WL, Sequeira DJ, Cawley GF, Eyer CS. Relationship between hydrocarbon structure and induction of P450: effects on protein levels and enzyme activities. Xenobiotica; The Fate of Foreign Compounds in Biological Systems 1993; 23(12): 1353–1366.
21. Roberts RA, Laskin DL, Smith CV, Robertson FM, Allen EM, Doorn JA, Slikker W. Nitrative and oxidative stress in toxicology and disease. Toxicol Sci: An Official Journal of the Society of Toxicology 2009; 112(1): 4–16.
22. Ayoubi M, Naserzadeh P, Hashemi MT, Reza Rostami M, Tamjid E, Tavakoli MM, Simchi A. Biochemical mechanisms of dose-dependent cytotoxicity and ROS-mediated apoptosis induced by lead sulfide/graphene oxide quantum dots for potential bioimaging applications. Sci Rep 2017; 7(1): 12896.
23. Victor VM, De la Fuente M. Immune cells redox state from mice with endotoxin-induced oxidative stress. Involvement of NF-kappaB. Free Radic Res 2003; 37(1): 19–27.
24. Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol & Med 2007; 42(2): 153–164.
25. El-Nabi Kamel, MA, Shehata M. Effect of toluene exposure on the antioxidant status and apoptotic pathway in organs of the rat. Br J Biomed Sci 2008; 65(2): 75–79.
26. Anyanwu BO, Orish CN, Ezejiofor AN, Nwaogazie IL, Akaranta O, Orisakwe OE. Multi-organ protective effect of Costus afer on low concentration toxic metal mixture in albino rats. Int J Physiol Pathophysiol & Pharmacol 2021; 13(2): 52–68.
27. Nygren J, Cedervall B, Eriksson S, Dusinská M, Kolman A. Induction of DNA strand breaks by ethylene oxide in human diploid fibroblasts. Environ. and Mol. Mutagen 1994; 24(3), 161–167.
28. Traber MG, Head B. Vitamin E: How much is enough, too much and why!. Free Radic. Biol. Med. 2021; 177 212-225.
29. Gupta, S, Kumar, D, Rauthan, JVS, Kamal, B (2022). Hepatoprotective Effect of Vitamin-E (α-Tocopherol) on Trichloroethylene and Toluene Induce Liver Damage in Rats. J. Mountain Res 17(2), 199-204.
30. Dewry, RKr, Deka, BC, Biswas RK, Bhuyan D, Borah, P, Mahanta, N, Kurmi, N (2020). Effect of butylated hydroxy toluene and vitamin e on the cryosurvivability of buck semen. CryoLetters 41 (2), 68-74.
31. Szymańska, R., Nowicka, B., Trela, A. and Kruk, J., 2020. Vitamin E: Structure and forms. In Molecular nutrition. Academic Press. 67-90 p.
32. Ali SS, Ahsan H, Zia MK, Siddiqui T. and Khan FH. 2020. Understanding oxidants and antioxidants: Classical team with new players. J Food Biochem, 44(3), p.e13145.
33. Valgimigli, L. Lipid peroxidation and antioxidant protection. Biomolecules 2023; 13(9): 1291.
34. Tyuryaeva I. and Lyublinskaya, O. Expected and unexpected effects of pharmacological antioxidants. Int J Mol Sci 2023; 24(11): 9303.
35. Liao S, Omage SO., Börmel, L., Kluge, S., Schubert, M., Wallert, M., Lorkowski, S. Vitamin E and Metabolic Health: Relevance of Interactions with Other Micronutrients. Antioxidants (Basel, Switzerland) 2022; 11(9), 1785.
36. Zheng, H., Xu, Y., Liehn, E.A. and Rusu, M. Vitamin C as scavenger of reactive oxygen species during healing after myocardial infarction. International Journal of Molecular Sciences 2024; 25(6): 3114.
37. Islam, M.N., Rauf, A., Fahad, F.I., Emran, T.B., Mitra, S., Olatunde, A., Shariati, M.A., Rebezov, M., Rengasamy, K.R. and Mubarak, M.S. Superoxide dismutase: an updated review on its health benefits and industrial applications. Crit Rev in Food Sci and Nutr 2022; 62(26): 7282-7300.
38. Sarıkaya, E. and Doğan, S. Glutathione Peroxidase in Health. Glutathione system and oxidative stress in health and disease. IntechOpen. 49 p.
39. Kamat CD, Gadal S, Mhatre M, Williamson KS, Pye QN, Hensley K. Antioxidants in central nervous system diseases: preclinical promise and translational challenges. J. Alzheimer's Dis: JAD 2008;15(3), 473–493.
40. Muti AD, Pârvu AE, Muti LA, Moldovan R, Mureşan A. Vitamin E effect in a rat model of toluene diisocyanate-induced asthma. Clujul Medical 2016; 89(4): 499–505.
41. Demır M, Cicek M, Eser N, Yoldaş A, Sısman T. "Effects of Acute Toluene Toxicity on Different Regions of Rabbit Brain". Anal Cell Pathol 2017; 6.
42. Soares MV, Mesadri J, Gonçalves DF, Cordeiro LM, Franzen da Silva A, Baptista FBO, Wagner R, Corte CLD, Soares FAA, Ávila DS. Neurotoxicity induced by toluene: In silico and in vivo evidences of mitochondrial dysfunction and dopaminergic neurodegeneration. Environ Pollut 2022; 298.
43. Baydas, G., Ozveren, F., Tuzcu, M. and Yasar, A. Effects of thinner exposure on the expression pattern of neural cell adhesion molecules, level of lipid peroxidation in the brain and cognitive function in rats. Eur J Pharmacol 2005; 512(2-3): 181-187.
44. Fifel, K., Bennis, M. and Ba-M’hamed, S., 2014. Effects of acute and chronic inhalation of paint thinner in mice: behavioral and immunohistochemical study. Metab brain dis 2014; 29: 471-482.
45. Folarin RO, Omirinde JO, Gilbert TT, Igbeneghu C. Acute and Sub-chronic Toxicity of Aqueous Extract of Roots of Khaya senegalensis (Desr.) A. Juss. in Mice and Rats Respectively. Annu. Res Rev Biol 2023; 38(8): 33–46.
46. Morton DB, Griffiths PH. Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment. Veter Rec. 1985;116: 431–436.
47. Baumans V, Brain PF, Brugere H, Clausing P, Jeneskog T, Perretta G. Pain and distress in laboratory rodents and lagomorphs. Report of the Federation of European Laboratory Animal Science Associations (FELASA) Working Group on Pain and Distress accepted by the FELASA Board of Management November 1992. Lab Anim 1994; 28:97–112.
48. Talbot SR, Biernot S, Bleich A. Defining body-weight reduction as a humane endpoint: a critical appraisal. Lab Anim. 2020; 54(1):99–110.
49. Martínez-Alfaro M, Cárabez-Trejo A, Gallegos-Corona MA, Pedraza-Aboytes G, Hernández-Chan NG, Leo-Amador GE. Thinner inhalation effects on oxidative stress and DNA repair in a rat model of abuse. J of Appl Toxicol: JAT 2010; 30(3): 226–232.
50. Malloul H, Mahdani FM, Bennis M, Ba-M'hamed S. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice. Front. Behav. Neurosci 2017; 11: 171.
51. Brohi, HA, Saeed A, Shams O, Al Jundi, EZ, Alreshi MN, Abualela H, Khotani A, Babakkor M. "glue sniffing neuropathy and review of literature," Pak J Neurol Sci 2013; 8(1)3: 8 -11.
52. Lopez-Lopez V, Garcia-Carrillo N, de Gea D, Oltra L, González-Bermúdez CA, et al. Assessment of hepatic function, perfusion and parenchyma attenuation with indocyanine green, ultrasound and computed tomography in a healthy rat model: Preliminary determination of baseline parameters in a healthy liver. PLOS ONE 2021;16(12): e0261447.
53. Rahimi HR, Agin K, Shadnia S, Hassanian-Moghaddam H, Oghazian MB. Clinical and biochemical analysis of acute paint thinner intoxication in adults: a retrospective descriptive study. Toxicol Mech Methods 2015; 25(1): 42–47.
54. Lala V, Zubair M, Minter DA. Liver function tests. [Updated 2023 Jul 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from https://www.ncbi.nlm.nih.gov/books/NBK482489/
55. Rizvi S, Raza ST, Ahmed F, Ahmad A, Abbas S, Mahdi F. The role of vitamin E in human health and some diseases. SQUMJ 2014; 14(2): e157–e165.
56. Sekihashi K, Yamamoto A, Matsumura Y, Ueno S, Watanabe-Akanuma M, Kassie F, Knasmüller S, Tsuda S, Sasaki YF. Comparative investigation of multiple organs of mice and rats in the comet assay. Mutation Res 2002; 517(1-2): 53–75.
57. Upperman JS, Bucuvalas JC, Williams FN, Cairns BA, Cox CS Jr, Doctor A, Tamburro RF. Specific etiologies associated with the multiple organ dysfunction syndrome in children: Part 2. Pediatr Crit Care Med 2017; 18(3 Suppl 1): 58–66.
58. Latief M, Hassan Z, Wani ML, Abbas F, Farooq S. Automobile paint reducer induced acute kidney injury: A case series. JRENHEP 2021; 5(2): 10–13.
59. Pajaro-Castro N, Caballero-Gallardo K, Olivero-Verbel J. Toxicity and expression of oxidative stress genes in Tribolium castaneum induced by toluene, xylene, and thinner. J Toxicol Environ Health. Part A 2019; 82(1): 28–36.
60. Tas U, Ogeturk M, Meydan S, et al. Hepatotoxic activity of toluene inhalation and protective role of melatonin. Toxicology and Industrial Health. 2011; 27(5):465–473.
61. Bansal AK, Bansal M, Soni G, Bhatnagar D. Protective role of Vitamin E pre-treatment on Nnitrosodiethylamine induced oxidative stress in rat liver. Chem Biol Interact 2005; 156(2-3): 101–111.
62. Baltusnikiene A, Staneviciene I, Jansen E. Beneficial and adverse effects of vitamin E on the kidney. Front Physiol, 2023; 14: 1145216.
63. Voloshin VN, Koveshnikov VG, Voloshina IS. Morphology of the spleen in adult albino rats after wholebody exposure to low-level of toluene. Int J Anat Res 2014; 2: 421–430.
64. Zaidi SA, Shaw AN, Patel MN, Shah VV, Rajendran D, Shah BP, Sinha SN, Gandhi SJ, Saiyed HN. Multiorgan toxicity and death following acute unintentional inhalation of paint thinner fumes. Clin Toxicol 2007; 45(3): 287–289.
65. Kanter, M. Thymoquinone attenuates lung injury induced by chronic toluene exposure in rats. Toxicol Ind Health 2011; 27: 387-395.