Author(s):
N.N. Gavrilova, I.A. Ratnikova, A.K. Sadanov, S.E. Orazymbet, E.Zh. Shorabaev, B.B. Baimakhanova, L.E. Protasiuk
Email(s):
iratnikova@list.ru
DOI:
10.52711/0974-360X.2023.00682 
Address:
N.N. Gavrilova1, I.A. Ratnikova1*, A.K. Sadanov1, S.E. Orazymbet1, E.Zh. Shorabaev2, B.B. Baimakhanova1, L.E. Protasiuk1
1Research and Production Center for Microbiology and Virology, 105 Bogenbai Batyr str., Almaty, 050010, Kazakhstan.
2Industrial Microbiology LLP, 89/44 Al-Farabi ave., Almaty, 050060, Kazakhstan.
*Corresponding Author
Published In:
Volume - 16,
Issue - 9,
Year - 2023
ABSTRACT:
Studies were conducted on the toxicity and possible sensitizing effect of the lyophilizate of a therapeutic probiotic agent from the most active strains of lactic acid and propionic acid bacteria isolated from healthy people: L. plantarum 2v/A-6+L. brevis B-3/A-26+L. acidophilus 27w/60+P. shermanii 8. Based on the studies conducted to evaluate acute toxicity with an oral single administration of probiotic agent solutions (lyophilizate of lactic acid and propionic acid bacteria) at doses of 300, 2,000, 4,000, and 5,001mg/kg of weight, the toxicity class of the preparation under study has been defined as a non-toxic substance. In the study on laboratory mice of subchronic (subacute) toxicity of probiotic agent (lyophilizate of lactic acid and propionic acid bacteria)) in doses of 5.0×106, 10.0×106, and 15.0×106 CFU, it has been found that the preparation does not have a toxic effect on the body in case of 28-day use. Studies of the chronic toxicity of the probiotic agent (lyophilizate of lactic acid and propionic acid bacteria) in doses of 5.0×106, 10.0×106, and 15.0×106 CFU, in laboratory mice have shown that this preparation does not have a toxic effect on the body in case of prolonged 60-day use and does not cause structural changes in internal organs. It has been established that the therapeutic probiotic agent (lyophilizate of lactic acid and propionic acid bacteria) does not have a potential sensitizing (allergenic) effect on rat peritoneal mast cells.
Cite this article:
N.N. Gavrilova, I.A. Ratnikova, A.K. Sadanov, S.E. Orazymbet, E.Zh. Shorabaev, B.B. Baimakhanova, L.E. Protasiuk. Determination of the Toxicity and Sensitizing effect of a Therapeutic Probiotic agent against Intestinal and Concomitant human infections. Research Journal of Pharmacy and Technology 2023; 16(9):4161-1. doi: 10.52711/0974-360X.2023.00682
Cite(Electronic):
N.N. Gavrilova, I.A. Ratnikova, A.K. Sadanov, S.E. Orazymbet, E.Zh. Shorabaev, B.B. Baimakhanova, L.E. Protasiuk. Determination of the Toxicity and Sensitizing effect of a Therapeutic Probiotic agent against Intestinal and Concomitant human infections. Research Journal of Pharmacy and Technology 2023; 16(9):4161-1. doi: 10.52711/0974-360X.2023.00682 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2023-16-9-26
REFERENCES:
1. Zam W. Dawod R. Overview of the Probiotics’ role in Gastrointestinal disorders. Research J. Pharm. and Tech. 2020; 13(11):5557-5561. doi: 10.5958/0974-360X.2020.00970.1
2. Dewi NP, Poddar S. Rai RP. Purwati E. Abdullah D. Pratama YE. The Potential Lactic Acid Bacteria from Dadiah Sianok Bukittinggi City, West Sumatera as Probiotic. Research J. Pharm. and Tech. 2023; 16(2):627-4. doi: 10.52711/0974-360X.2023.00107
3. Thu TTM. Vinh DTT. Dung NA. Tu NHK. Effect of Lactic Acid produced by Lactic acid bacteria on Prodigiosin production from Streptomyces coelicolor. Research J. Pharm. and Tech. 2021; 14(4):1953-6. doi: 10.52711/0974-360X.2021.00345
4. Sivaraj A. Kumar V. Kalyanasundaram R. Kasivelu G. Biogenic production of Gold nanoparticles using Lactic acid bacteria and their Anti-mycobacterial activity. Research J. Pharm. and Tech. 2020; 13(9):4391-4394. doi: 10.5958/0974-360X.2020.00776.3
5. Hossain MK. Nahar K. Shokryazdan P. Abdullah N. Hamid K. Jahromi MF. Probiotic Potential of Lactic Acid Bacteria Isolated from Cheese, Yogurt and Poultry Faeces. Research J. Pharm. and Tech. 2017; 10(9):2991-2998. doi: 10.5958/0974-360X.2017.00530.3
6. Nugraha D. Putri NAS. Visuddho, Wungu CDK. Comparison of Bacterial Composition, Concentration, and Metabolism of Short Chain Fatty Acid in Inflammatory Bowel Disease: A Systematic Review. Research J. Pharm. and Tech. 2021; 14(11):5978-4. doi: 10.52711/0974-360X.2021.01038
7. Kasatkin M. Smirnova L. Babaskin D. Therapeutic effects of Probiotic Ointment for Atopic Dermatitis. Research J. Pharm. and Tech. 2021; 14(11):6041-8. doi: 10.52711/0974-360X.2021.01050
8. Namasivayam SKR. Kumar SN., Mohan CS. Gayathri V. Biocompatible formulation of Probiotic bacteria Bacillus subtilis with agriculture based Products for the effective acid Tolerance Properties and Synergistic activity with Antibiotics. Research J. Pharm. and Tech. 2018; 11(1): 73-78 doi: 10.5958/0974-360X.2018.00014.8
9. Chauhan A. Kaur S. Singh R. A Review on Probiotics and Fish Farming. Research J. Pharm. and Tech. 2018; 11(11):5143-5146. doi: 10.5958/0974-360X.2018.00939.3
10. Triwardhani A. Oktaviona I. Narmada IB. Nugraha AP. The Effect of Bifidobacterium Probiotic on Heat Shock Protein-70 Expression and Osteoclast Number during Orthodontic Tooth Movement in Rats (Rattus novergicus). Research J. Pharm. and Tech. 2021; 14(3):1477-1481. doi: 10.5958/0974-360X.2021.00262.6
11. Didari T. Solki S. Mozaffari S. Nikfar S. Abdollahi M. A systematic review of the safety of probiotics. Expert Opinion on Drug Safety. 2014 Feb; 13(2):227-39. doi: 10.1517/14740338.2014.872627
12. Senok AC. Ismaeel AY. Botta GA. Probiotics: facts and myths. Clinical Microbiology and Infection. 2005 Dec; 11(12):958–66. doi: 10.1111/j.1469-0691.2005.01228.x
13. Abatenh E. Gizaw B. Tsegay Z. Tefera G. Aynalem E. Health benefits of probiotics. Journal of Bacteriology and Infectious Diseases. 2019; 2(1):8-27.
14. Abdelmoneim E. Refat E. James K. Alnajmalthageb M. Eldein SD. Mekaiel MA. Eltegani SEA. Evolution of the use and manufacturing of lactic acid bacteria probiotic and its effect on human health. European Journal of Biomedical and Pharmaceutical Sciences. 2022; 9(9):1-27.
15. Salyers AA. Gupta A. Wang Y. Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends in Microbiology. 2004 Sep; 12(9):412-6. doi: 10.1016/j.tim.2004.07.004
16. Snydman DR. The safety of probiotics. Clinical Infectious Diseases. 2008 Feb 1; 46(SUPPL. 2): S104-11. doi: 10.1086/523331
17. Bang WY. Ban OH. Lee BS. Oh S. Park C. Park MK. Jung SK. Yang J. Jung YH. Genomic-, phenotypic-, and toxicity-based safety assessment and probiotic potency of Bacillus coagulans IDCC 1201 isolated from green malt. Journal of Industrial Microbiology and Biotechnology. 2021 Jul 1; 48(5–6):kuab026. doi: 10.1093/jimb/kuab026
18. Connolly E. Abrahamsson T. Björkstén B. Safety of D(-)-lactic acid producing bacteria in the human infant. Journal of Pediatric Gastroenterology and Nutrition. 2005 Oct; 41(4):489-92. doi: 10.1097/01.mpg.0000176179.81638.45
19. Levitt MD. Levitt DG. Quantitative evaluation of d-lactate pathophysiology: new insights into the mechanisms involved and the many areas in need of further investigation. Clinical and Experimental Gastroenterology. 2020 Sep 8; 13:321-37. doi: 10.2147/CEG.S260600
20. Yilmaz B. Schibli S. Macpherson AJ. Sokollik C. D-lactic acidosis: successful suppression of D-lactate-producing lactobacillus by probiotics. Pediatrics. 2018 Sep; 142(3):e20180337. doi: 10.1542/peds.2018-0337
21. Vitetta L. Vitetta G. Hall S. Immunological tolerance and function: associations between intestinal bacteria, probiotics, prebiotics, and phages. Frontiers in Immunology. 2018 Oct 9; 9:2240. doi: 10.3389/fimmu.2018.02240
22. Qureshi N. Gu Q. Li P. Whole genome sequence analysis and in vitro probiotic characteristics of a Lactobacillus strain Lactobacillus paracasei ZFM54. Journal of Applied Microbiology. 2020 Aug; 129(2):422-33. doi: 10.1111/jam.14627
23. Meleh HU. Choo S. Nasir Mohd Desa M. Chew SY. Rangasamy R. Hassan H. Than LTL. Isolation and safety characterisation of lactobacilli strains with antimicrobial properties as potential probiotics for human use. Lebensmittel-Wissenschaft und-Technologie. 2020; 131:109796. doi: 10.1016/j.lwt.2020.109796
24. Morovic W. Roper JM. Smith AB. Mukerji P. Stahl B. Rae JC. Ouwehand AC. Safety evaluation of HOWARU® restore (lactobacillus acidophilus NCFM, lactobacillus paracasei Lpc-37, bifidobacterium animalis subsp. lactis Bl-04 and B. lactis Bi-07) for antibiotic resistance, genomic risk factors, and acute toxicity. Food and Chemical Toxicology. 2017 Dec; 110:316-24. doi: 10.1016/j.fct.2017.10.037
25. Mangalat N. Liu Y. Fatheree NY. Ferris MJ. Van Arsdall MR. Chen Z. Rahbar MH. Gleason WA. Norori J. Tran DQ. Rhoads JM. Safety and tolerability of lactobacillus reuteri DSM 17938 and effects on biomarkers in healthy adults: results from a randomized masked trial. PLoS One. 2012; 7(9):e43910. doi: 10.1371/journal.pone.0043910
26. Allen SJ. Jordan S. Storey M. Thornton CA. Gravenor M. Garaiova I. Plummer SF. Wang D. Morgan G. Dietary supplementation with lactobacilli and bifidobacteria is well tolerated and not associated with adverse events during late pregnancy and early infancy. The Journal of Nutrition. 2010 Mar; 140(3):483-8. doi: 10.3945/jn.109.117093
27. Olivares M. Castillejo G. Varea V. Sanz Y. Double-blind, randomised, placebo-controlled intervention trial to evaluate the effects of Bifidobacterium longum CECT 7347 in children with newly diagnosed coeliac disease. British Journal of Nutrition. 2014 Jul 14; 112(1):30-40. doi: 10.1017/S0007114514000609
28. Belova IV. Tochilina AG. Soloveva IV. Zhilenkova OG. Melikhova AV. Belyaeva EV. Ermolina GB. Boriskina EV. Zhirnov VA. Ivanova TP. The results of «LB-complex L» immobilized synbiotic safety study in animals. International Journal of Applied and Fundamental Research. 2018; 2: 85-89. doi: 10.17513/mjpfi.12113
29. Kalliomäki M. Antoine JM. Herz U. Rijkers GT. Wells JM. Mercenier A. Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics. The Journal of Nutrition. 2010 Mar; 140(3):713-21. doi: 10.3945/jn.109.113761
30. Majamaa H. Isolauri E. Probiotics: a novel approach in the management of food allergy. The Journal of Allergy and Clinical Immunology. 1997 Feb; 99(2):179-85. doi: 10.1016/s0091-6749(97)70093-9
31. Castellazzi AM. Valsecchi C. Caimmi S. Licari A. Marseglia A. Leoni MC. Caimmi D. Miraglia del Giudice M. Leonardi S. La Rosa M. Marseglia GL. Probiotics and food allergy. Italian Journal of Pediatrics. 2013 Jul 29; 39:47. doi: 10.1186/1824-7288-39-47
32. Mennini M. Dahdah L. Artesani MC. Fiocchi A. Martelli A. Probiotics in asthma and allergy prevention. Frontiers in Pediatrics. 2017 Jul 31; 5:165. doi: 10.3389/fped.2017.00165
33. Prikaz i.o. Ministra zdravookhraneniya Respubliki Kazakhstan ot 4 fevralya 2021 goda No. ҚR DSM-15 “Ob utverzhdenii nadlezhashchikh farmatsevticheskikh praktik”, zaregistrirovan v Ministerstve yustitsii RK 9 fevralya 2021 goda [Order No. KR DSM-15 issued by the Deputy Minister of Health of the Republic of Kazakhstan dated February 4, 2021 “On approval of good pharmaceutical practices”, registered with the Ministry of Justice of the Republic of Kazakhstan on February 9, 2021]. Available at: https://adilet.zan.kz/rus/docs/V2100022167
34. OECD. Test No. 423: Acute oral toxicity - acute toxic class method. OECD guidelines for the testing of chemicals, Section 4. OECD Publishing, Paris. 2002 Feb 8; 14 p. doi: 10.1787/9789264071001-en
35. OECD. Test No. 408: Repeated dose 90 - day oral toxicity study in rodents. OECD guidelines for the testing of chemicals, Section 4. OECD Publishing, Paris. 2018 Jun 27; 16 p. doi: 10.1787/9789264070707-en
36. Mironov AN. Metodicheskie rekomendatsii po otsenke allergiziruyushchikh svoistv lekarstvennykh sredstv [Guidelines for assessing the allergenic properties of medications]. In Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Chast pervaya [Guidelines for conducting preclinical medication studies. Part one]. Grif i K, Moscow. 2012; 51-63.
37. Li P. Tian W. Jiang Z. Liang Z. Wu X. Du B. Genomic characterization and probiotic potency of bacillus sp. DU-106, a highly effective producer of L-Lactic acid isolated from fermented yogurt. Frontiers in Microbiology. 2018 Sep 20; 9:2216. doi: 10.3389/fmicb.2018.02216
38. Ling W. Li S. Zhang X. Xu Y. Gao Y. Du Q. Wang G. Fan W. Sun K. Bian J. Evaluation of anti-obesity activity, acute toxicity, and subacute toxicity of probiotic dark tea. Biomolecules. 2018 Sep 25; 8(4):99. doi: 10.3390/biom8040099
39. Holzapfel W. Arini A. Aeschbacher M. Coppolecchia R. Pot B. Enterococcus faecium SF68 as a model for efficacy and safety evaluation of pharmaceutical probiotics. Benefial Microbes. 2018 Apr 25; 9(3):375-88. doi: 10.3920/BM2017.0148