1. bookVolume 72 (2022): Issue 2 (June 2022)
Journal Details
License
Format
Journal
eISSN
1820-7448
First Published
25 Mar 2014
Publication timeframe
4 times per year
Languages
English
access type Open Access

Effects of Diazepam on Hematological and Histological Parameters in Rats / in Vivo and Unbiased Stereological Investigation

Published Online: 04 Jul 2022
Volume & Issue: Volume 72 (2022) - Issue 2 (June 2022)
Page range: 235 - 255
Accepted: 24 May 2022
Journal Details
License
Format
Journal
eISSN
1820-7448
First Published
25 Mar 2014
Publication timeframe
4 times per year
Languages
English
Abstract

Diazepam-based drugs are widely used today in human treatment. Diazepam may be a primary drug aimed at treating neurological diseases or an associated drug in the treatment of other diseases in the purpose of symptomatic therapy. The sedative effect of diazepam characterizes it as a drug that people usually use on their own and without a doctor’s supervision. Directly, but also through influencing the nervous system, diazepam disrupts proper functioning of all body organs. The purpose of this paper was to examine the effects of diazepam on blood and cytohistological parameters of rats in an in vivo experiment. Mallory-Azan and immunochistochemical staining methods BLX-CX and Survivin tissues of liver, kidney and spleen of rats were used to achieve the set goal. Cytometric analysis of rats detected cells in apoptosis and measurements of stereological parameters were made using a system according to Cavalier’s principle. Results of analysis of hematological and histological parameters indicate a detrimental effect of diazepam on blood parameters, as well as on structure and functioning of the liver, kidneys and spleen of rats. This paper is a foundation for further detailed scientific research with the aim of elucidating all harmful effects that diazepam has on all organs in the body of rats. This data could serve as a starting point for future studies in clinical pharmacology on therapeutic protocols for usage of diazepam-based sedatives.

Keywords

1. Sevastre-Berghian AC, Fägäräsan V, Toma VA, Baldea I, Olteanu D, Moldovan R, Decea N, Filip GA, Clichici SV: Curcumin Reverses the Diazepam-Induced Cognitive Impairment by Modulation of Oxidative Stress and ERK 1/2/NF-κB Pathway in Brain. Oxid Med Cell Longev 2017, 2017(3): 3037876.10.1155/2017/3037876 Search in Google Scholar

2. Olfson M, King M, Schoenbaum M: Benzodiazepine use in the United States. JAMA Psychiatry 2015, 72(2):136–142.10.1001/jamapsychiatry.2014.1763 Search in Google Scholar

3. Amorim CG, Araújo AN, Montenegro SM, Silva VL: Cyclodextrin-based potentiometric sensors for midazolam and diazepam. J Pharm Biomed Anal 2008, 48(4):1064–1069.10.1016/j.jpba.2008.08.012 Search in Google Scholar

4. Šegrt Z, Đorđević S, Jaćević V, Kilibarda V, Vučinić S, Jović-Stošić J, Potrebić O, Perković-Vukčević N: Farmakodinamski i farmakokinetski efekti primene flumazenila i teofilina kod pacova akutno trovanih diazepamom. Vojnosanit Pregl 2009, 66(2):141-148. Search in Google Scholar

5. Ashton H: The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry 2005, 18(3):249–255.10.1097/01.yco.0000165594.60434.84 Search in Google Scholar

6. Mimica N, Folnegović-Šmalc V, Uzun S, Rušinović M: Benzodiazepini: za i protiv. Med Psihofarmak 2002, 11(2):183–188. Search in Google Scholar

7. Malcolm RJ: GABA Systems, Benzodiazepines, and Substance Dependence. J Clin Psychiatry 2003, 64(3):36-40. Search in Google Scholar

8. Honeychurch KC, Hart JP: Electrochemical Detection of Benzodiazepines, Following Liquid Chromatography, for Applications in Pharmaceutical, Biomedical and Forensic Investigations. Insciences J 2014, 4(1):1-18.10.5640/insc.040101 Search in Google Scholar

9. Owen G, Smith THF, Agersborg HPK: Toxicity of some benzodiazepine compounds with CNS activity. Toxicol. Appl. Pharmacol 1970, 16(2):556–570.10.1016/0041-008X(70)90031-1 Search in Google Scholar

10. Pomares FB, Funck T, Feier NA, Roy S, Daigle-Martel A, Ceko M, Narayanan N, Araujo D, Thiel A, Stikov N, Fitzcharles MA, Schweinhardt P: Histological Underpinnings of Grey Matter Changes in Fibromyalgia Investigated Using Multimodal Brain Imaging. J Soc Neurosci 2017, 37(5):1090–1101.10.1523/JNEUROSCI.2619-16.2016 Search in Google Scholar

11. Anber ZNH, Fadhil AA, Anber SA: The biochemicl and histological effect of diazepam on the liver of albino male rats. Internat J Acad Res Reflec 2018, 6(3). Search in Google Scholar

12. Ilesanmi OB, Odewale TT: Effect of classic soft drink Coca-Cola as a solvent in the administration of tramadol and diazepam on biochemical and histological changes in liver and kidney. Ukr J Nephrol Dial 2020, 3(67).10.31450/ukrjnd.3(67).2020.06 Search in Google Scholar

13. Setiawan PGM, Tunjung WAS, Nurhidayat L: Effect of diazepam on kidney function and histological structure of white rats kidney. J Biol Res 2016, 22(1):6.10.23869/bphjbr.22.1.20161 Search in Google Scholar

14. Al-Rekabi AE, Al-Rumaidh SZ, Al-Fartosi KG: Effect of tramadol and diazepam on some biochemical parameters of male rats. J Nat Remed 2021, 21(12):1-12. Search in Google Scholar

15. Nestorović N, Trifunović S, Ivana J, Manojlović-Stojanovski M, Ristić N, Filipović B, Šošić-Jurnjević B, Milošević V: Sex steroid application reverses changes in rat castration cells: Unbiased stereological analysis. Arch Biol Sci 2016, 68(4):821–828. Search in Google Scholar

16. Paraš S, Janković O, Trišić D, Čolović B, Mitrović-Ajtić O, Dekić R, Soldatović I, Živković-Sandić M, Živković S, Jokanović V: Influence of nanostructured calcium aluminate and calcium silicate on the liver: histological and unbiased stereological analysis. Int Endod J 2019, 52(8):1162–1172.10.1111/iej.1310530802977 Search in Google Scholar

17. Santos M, Marcos R, Santos N, Malhão F, Monteiro RAF, Rocha E: An unbiased stereological study on subpopulations of rat liver macrophages and on their numerical relation with the hepatocytes and stellate cells. J Anat 2009, 214(5):744–751.10.1111/j.1469-7580.2009.01055.x Search in Google Scholar

18. Sharp P, Villano JS: The Laboratory Rat. Routledge & CRC Press 2012.10.1201/b13862 Search in Google Scholar

19. Sasse EA: How to define and determine reference intervals in the clinical laboratory approved guideline. Wayne Pa NCCLS 1995. Search in Google Scholar

20. Goel N, Bale TL: Organizational and Activational Effects of Testosterone on Masculinization of Female Physiological and Behavioral Stress Responses. Endocrinology 2008, 149(12):6399–6405.10.1210/en.2008-0433 Search in Google Scholar

21. Elusiyan CA, Faria ALG, Mendes AEQ, Silva IO, Martins JLR, Rosa DA, Pedrino GR, Costa EA, Ibrahim MA, Zjawiony JK, Fejemiroye JO: Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice. Planta Med 2020, 86(16):1204–1215.10.1055/a-1209-1254 Search in Google Scholar

22. Mohammad RA, Shukhi K, Lalin M, Zunayeed R, Mostafa A, Mohammad LM: Evaluation of some prescribed and over-the-counter drugs induced hemato-biochemical changes in mice. Asian J Med Biolog Res 2019, 5(4).10.3329/ajmbr.v5i4.45268 Search in Google Scholar

23. Kamel M: Neurochemical, hematological and behavioral alterations related to eszopiclone administration in rats. Slovenian Vet Res 2018, 55:41-50. Search in Google Scholar

24. Osonuga I, Osonuga O, Osonuga A, Onadeko A, Osonuga A: Effect of artemether on hematological parameters of healthy and uninfected adult Wistar rats. Asian Pac J Trop Biomed 2012, 2(6):493–495.10.1016/S2221-1691(12)60083-5 Search in Google Scholar

25. Nzor JN, Uwakwe AA, Onuoha SC: Impact of benzodiazepines administration on selected biochemical parameters of albino Wistar rats (Rattus rattus). Egyptian Pharm J 2018, 17(1):40-47.10.4103/epj.epj_26_17 Search in Google Scholar

26. Anacletus FC, Onyegeme-Okerenta BM: Evaluation of the influence of therapeutic, prolonged and overdose intake of diazepam on hematological indices and liver emzyme markers of male Wistar rats. Res J Life Sci Bioinforma Pharm Chem Sci 2017, 2(6). Search in Google Scholar

27. Fernández NH, Zanetti SR, Báez NS, Bibolini MJ, Bouzat C, Roth GA: Diazepam treatment reduces inflammatory cells and mediators in the central nervous system of rats with experimental autoimmune encephalomyelitis. J. Neuroimmunol 2017, 313:145–151.10.1016/j.jneuroim.2017.09.012 Search in Google Scholar

28. Bellomo R, Kellum JA, Ronco C: Acute kidney injury. Lancet Lond Engl 2012, 380(9843):756–766.10.1016/S0140-6736(11)61454-2 Search in Google Scholar

29. Khajuria A, Tay C, Shi J, Zhao H, Ma D: Anesthetics attenuate ischemia–reperfusion induced renal injury: Effects and mechanisms. Acta Anaesthesiol Taiwan 2014, 52(4):176–184.10.1016/j.aat.2014.10.00125477261 Search in Google Scholar

30. Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, Bogardus C, Tataranni PA: High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 2002, 51(6):1889–1895.10.2337/diabetes.51.6.188912031978 Search in Google Scholar

31. Bian T, Corral P, Wang Y, Botello J, Kingston R, Daniels T, Salloum RG, Johnston E, Huo Z, Lu J, Liu AC, Xing C: Kava as a Clinical Nutrient: Promises and Challenges. Nutrients 2020, 12(10):3044.10.3390/nu12103044760051233027883 Search in Google Scholar

32. De P, Pang T, Das G: Clinical Implications and Management of Sub Clinical Hyperthyroidism: A Review. Open J Endocr Metab Di 2012, 2(3):27–35.10.4236/ojemd.2012.23004 Search in Google Scholar

33. Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U: Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. J Biosci 2005. 30(2):245–252.10.1007/BF0270370515886461 Search in Google Scholar

34. Abed A, Minaiyan M, Safaei A, Taheri D: Effect of Diazepam on Severity of Acute Pancreatitis: Possible Involvement of Peripheral Benzodiazepine Receptors. ISRN Gastroenterol 2013, 54:1–6.10.1155/2013/484128373021723956866 Search in Google Scholar

35. Akram M, Riaz M, Munir N, Akhter N, Zafar S, Jabeen F, Shariati MA, Akhtar N, Riaz Z, Altaf SH, Daniyal M, Zahir R, Khan FS: Chemical constituents, experimental and clinical pharmacology of Rosa damascena: a literature review. J Pharm Pharmacol 2020, 72(2):161–174.10.1111/jphp.1318531709541 Search in Google Scholar

36. Stevens CM, Rayani K, Singh G, Lotfalisalmasi B, Tieleman DP, Tibbits GF: Changes in the dynamics of the cardiac troponin C molecule explain the effects of Ca2+-sensitizing mutations. J Biol Chem 2017, 292(28):11915–11926.10.1074/jbc.M116.770776551208328533433 Search in Google Scholar

37. Al-Abbasi FA, Kumar V, Anwar F: Biochemical and toxicological effect of diazepam in stress-induced cardiac dysfunctions. Toxicol Rep 2020, 7:788–794.10.1016/j.toxrep.2020.06.004733443832642445 Search in Google Scholar

38. Griffin CE, Kaye AM, Bueno FR, Kaye AD: Benzodiazepine Pharmacology and Central Nervous System–Mediated Effects. Ochsner J 2013, 13(2):214–223. Search in Google Scholar

39. Supasai S, Gonzalez EA, Rowland DJ, Hobson B, Bruun DA, Guignet MA, Soares S, Singh V, Wulff H, Saito N, Harvey DJ, Lein PJ: Acute administration of diazepam or midazolam minimally alters long-term neuropathological effects in the rat brain following acute intoxication with diisopropylfluorophosphate. Eur J Pharmacol 2020, 886:173538.10.1016/j.ejphar.2020.173538757282032898549 Search in Google Scholar

40. El-Sokkary HG: Melatonin and vitamin C administration ameliorate diazepam-induced oxidative stress and cell proliferation in the liver of rats. Cell Prolif 2008, 1:168-76.10.1111/j.1365-2184.2007.00503.x649556018211292 Search in Google Scholar

41. Wang HJ, Benet LZ: Protein Binding and Hepatic Clearance: Re-Examining the Discrimination between Models of Hepatic Clearance with Diazepam in the Isolated Perfused Rat Liver Preparation. Drug Metab Dispos 2019, 47(12):1397–1402.10.1124/dmd.119.088872704271731563869 Search in Google Scholar

42. Mohame AS, Hosney M, Bassiony H, Hassanien SS, Soliman AM, Fahmy SR, Gaafar K: Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats. Sci Rep 2020, 10(1):378.10.1038/s41598-019-57252-7696236831942001 Search in Google Scholar

43. Bribes E, Casellas P, Vidal H, Dussossoy D, Casellas D: Peripheral Benzodiazepine Receptor Mapping in Rat Kidney. Effects of Angiotensin II-Induced Hypertension. J Am Soc Nephrol 2002, 13(1):1–9.10.1681/ASN.V131111752015 Search in Google Scholar

44. Howse MLP, Bell GM: Drugs and toxins that damage the kidney. Med Baltimore 2007, 35(7):399–403.10.1016/j.mpmed.2007.04.002 Search in Google Scholar

45. Crowe AV, Howse M, Bell GM, Henry JA: Substance abuse and the kidney. QJM Int J Med 2000, 93(3):147–152.10.1093/qjmed/93.3.14710751233 Search in Google Scholar

46. Ali AH, Zinad KH: Histopathological changes and immunosuppression induce by diazepam in mice. Al-Qadisiyah J Vet Med Sci 2014, 13(1).10.29079/vol13iss1art279 Search in Google Scholar

47. Sayed GM, Desoky N, El-Refaiy A, Abd-Elrahman IM, Nagy MH: Histological study on the stomach of immobilized-stressed albino rat and the curative role of diazepam. Egypt J Exp Biol Zool 2011, 7(2):153–161. Search in Google Scholar

48. Mousa AM: Light and electron microscopic study on the effect of diazepam on the cardiac muscle of adult albino rat and the possible role of garlic. Egypt J Histol 2014, 37(1):102–111.10.1097/01.EHX.0000444077.09624.b1 Search in Google Scholar

49. Bartolomucci A: Social stress, immune functions and disease in rodents. Front Neuroendocrinol 2007. 28(1):28–49.10.1016/j.yfrne.2007.02.00117379284 Search in Google Scholar

50. Huemer HP, Lassnig C, Nowotny N, Irschick EU, Kitchen M, Pavlic M: Diazepam leads to enhanced severity of orthopoxvirus infection and immune suppression. Vaccine 2010, 28(38):6152–6158.10.1016/j.vaccine.2010.07.03220659521 Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo