Microbiological Investigation of the Effects of Olanzapine with Thymoquinone on the Intestine

Year 2022, Volume: 12 Issue: 1, 106 - 119, 30.06.2022

Ayşe Nilay Güvenç Sebile Azirak Deniz Taştemir Korkmaz Sedat Bilgiç Nevin Kocaman Mehmet Kaya Özer

https://doi.org/10.37094/adyujsci.1088942

Abstract

The aim of our study is to examine the effect of thymoquinone (TQ) in obese rats induced with the antipsychotic drug olanzapine (OL). Thirty-five female Spraque-Dawley rats were divided into five groups (n = 7): Control, OL (2 mg / kg OL daily), OL + TQ1 (2 mg / kg OL + 20 mg / kg TQ), OL + TQ2 (2 mg / kg OL + 40 mg / kg TQ) and the OL + TQ3 group (2 mg / kg OL + 80 mg / kg TQ). On the 15th day of treatment, intestinal tissue was removed for analysis. It has been found that TQ treatment affects the levels of Firmicutes and Bacteroides at varying rates in the intestinal flora in OL + TQ1, OL + TQ2, and OL + TQ3 groups, and also has a significant role in the apoptotic effect of TQ. In conclusion, with this study, it was determined that the treatment of TQ has a protective property against the side effects of OL. TQ can be an effective treatment method to increase therapeutic effectiveness.

Keywords

Olanzapine, Thymoquinone, Obesity, Firmicutes, Bacteroides

Supporting Institution

Adıyaman Üniversitesi Bilimsel Araştırma Proje Birimi

Project Number

SHMYOMAP/2015-0002

Thanks

I would like to thank Assoc. Prof.Dr. Hesna YİĞİT, who helped me in microbiological calculations in this study.

Olanzapin ile Timokinon'un Bağırsak Üzerindeki Etkilerinin Mikrobiyolojik Olarak Araştırılması

Abstract

Çalışmamızın amacı, bir antipsikotik ilaç olanzapin (OL) ile indüklenen obez sıçanlarda timokinonun (TQ) etkisini incelemektir. Otuz beş dişi Spraque-Dawley sıçanı beş gruba ayrıldı (n = 7): Kontrol, OL (günlük 2 mg / kg OL), OL + TQ1 (2 mg / kg OL + 20 mg / kg TQ), OL + TQ2 (2 mg/kg OL + 40 mg/kg TQ) ve OL + TQ3 grubu (2 mg/kg OL + 80 mg/kg TQ). Tedavinin 15. gününde, analiz için bağırsak dokusu çıkarıldı. TQ tedavisinin, OL+TQ1, OL+TQ2 ve OL+TQ3 gruplarında bağırsak florasındaki Firmicutes ve Bacteroides düzeylerini değişen oranlarda etkilediği ve ayrıca TQ'nun apoptotik etkisinde önemli rolü olduğu tespit edilmiştir. Sonuç olarak, bu çalışma ile TQ tedavisinin OL'nin yan etkilerine karşı koruyucu özelliği olduğu belirlendi. TQ, terapötik etkinliği artırmak için etkili bir tedavi yöntemi olabilir.

Keywords

Olanzapin; Timokinon; Obezite; Firmicutes; Bacteroides.

Project Number

SHMYOMAP/2015-0002

References

• [1] Yıldırım, A.E., Altun, R., Obezite ve Mikrobiyota, Güncel Gastroenteroloji, 18(1) 106- 111, 2014.
• [2] Collaborators, G.O., Health effects of overweight and obesity in 195 countries over 25 years, The New England Journal of Medicine, 377(1): 13-27, 2017.
• [3] Finkelstein, E,A., Khavjou, O.A., Thompson, H., et al., Obesity and severe obesity forecasts through 2030, American Journal of Preventive Medicine, 42(6):563-70, 2012.
• [4] Walters, WA., Xu, Z., Knight, R., Meta- analyses of human gut microbes associated with obesity and IBD, FEBS Letters, 588(22): 4223-33, 2014.
• [5] Halk Sağlığı Genel Müdürlüğü. Dünyada Obezitenin Görülme Sıklığı. https://hsgm.saglik.gov.tr/tr/obezite/dunyada-obezitenin-gorulme-sikligi.html (Erişim tarihi: 2017).
• [6] Kaya, M., Sarıbaş, Z., Obezite ve Mikroorganizmalar, Hacettepe Tıp Dergisi, 38:173- 176, 2007.
• [7] Bull, M.J., Plummer, N.T., The human gut microbiome in health and disease, Journal of Integrative Medicine, 13(6): 17-22, 2014.
• [8] Karabudak, S., Arı, O., Durmaz, B., Dal, T., Basyigit, T., Kalcioglu, M.T., Durmaz, R., Analysis of the effect of smoking on the buccal microbiome using next generation sequencing technology, Journal of Medical Microbiology, 68 (8): 1148-1158, 2019.
• [9] Durmaz, B., Bağırsak mikrobiyotası ve obezite ile ilişkisi, Türk Hijyen ve Deneysel Biyoloji Dergisi, 76(3): 353-360, 2019.
• [10] Tseng, C.H., Wu, C.Y., The gut microbiome in obesity, Journal of the Formosan Medical Association, 118 (1): 3-9, 2018.
• [11] Castaner, O., Goday, A., Park, Y.M., Lee, S.H., Magkos, F., Shiow, S.A.T.E., Schröder, H., The Gut Microbiome Profile in Obesity: A Systematic Review, International Journal of Endocrinology, 2018: 9, 2018.
• [12] Qian, L.L., Li, H.T., Zhang, L., Fang, Q.C., Jia, W.P., Effect of the Gut microbiota on obesity and its underlying mechanisms: an update, Biomedical and Environmental Sciences, 28(11):839-47, 2015.
• [13] Shreiner, A.B., Kao, J.Y., Young, V.B., The gut microbiome in health and in disease, Current Opinion in Gastroenterology, 31(1): 69-5, 2015.
• [14] Bilgiç, S., Korkmaz, D.T., Azirak, S., Guvenc, A.N., Kocaman, N., Özer, M.K., The protective effect of thymoquinone over olanzapineinduced side effects in liver, and metabolic side effects, Bratislava Medical Journal, 118 (10) 618 – 625, 2017.
• [15] Abde Fattah, A.F.M., Matsumoto, K., Watanabe H., Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone in mice, European Journal of Pharmacolog, 400: 89-9, 2000.
• [16] Albaugh, V.L., Henry, C.R., Bello, N.T., Hajnal, A., Lynch, S.L., Halle, B., Lynch, C.J., Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents, Obesity (Silver Spring), 14: 36–51, 2006.
• [17] Prabhakar, P., Reeta, K.H., Maulik, S.K., Dinda, A.K., Gupta, Y.K., Protective effect of thymoquinone against high-fructose diet-induced metabolic syndrome in rats, European Journal of Nutrition, 54 (7): 1117–27, 2015.
• [18] Tas, U., Ayan, M., Sogut, E., Kuloglu, T., Uysal, M., Tanriverdi, H., 5, Senel, U., Ozyurt, B., Sarsilmaz, M., Protective effects of thymoquinone and melatonin on intestinal ischemia–reperfusion injury, Saudi Journal of Gastroenterology, 21: 284–289, 2015.
• [19] Can, N., Catak, O., Turgut. B., Demir, T., Ilhan, N., Kuloglu, T., Ozercan, İ.H., Neuroprotective and antioxidant effects of ghrelin in an experimental glaucoma model, Drug Design, Development and Therapy, 2(9): 2819–2829, 2015.
• [20] https://www.youtube.com/watch?v=GQOnX1-SUrI).
• [21] http://www.rapidtables.com/calc/math/Exponent_Calculator.htm
• [22] Yıldız, Ş., Turan, S., Timokinon, Timol ve Karvakrolün Antioksidan Aktiviteleri ve Lipit Oksidasyonunu Önleme Kapasiteleri, Atatürk Üniversitesi Ziraat Fakültesi Dergisi, 52 (1): 108-118, 2021. [23] Nagi, M.N., Mansour, M.A., Protective effect of thymoquinone against doxorubicin– induced cardiotoxicity in rats: a possible mechanism of protection, Pharmacological Research, 41 (3): 283-289, 2000.
• [24] Mansour, M.A., Nagi, M.N., El- Khatib, A.S., Al-Bekairi, A.M., Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT- diaphorase in different tissues of mice: A possible mechanism of action. Cell Biochemistry and Function, 20 (2): 143-151, 2002.
• [25] Badary, O.A., Taha, R.A., Gamal, E.D., Abdel-Wahab, M.H., Thymoquinone is a potent superoxide anion scavenger, Drug and Chemical Toxicology, 26 (2): 87-98, 2003.
• [26] Bourgou, S., Pichette, A., Marzouk, B., Legault, J., Bioactivities of black cumin essential oil and its main terpenes from Tunisia, South African of Botany, 76: 210-216, 2010.
• [27] Ahmad, S., Beg, Z.H., Hypolipidemic and antioxidant activities of thymoquinone and limonene in atherogenic suspension fed rats, Food Chemistry, 138 (2-3): 1116-1124, 2013.
• [28] Jumpertz, R., Le, D.S., Turnbaugh, P.J., Trinidad, C., Bogardus, C., Gordon, J.I., Krakoff, J., Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans, American Journal of Clinical Nutrition, 94(1): 58-65, 2011.
• [29] Zhang, Y.J., Li, S., Gan, R.Y., Zhou, T., Xu, D.P., Li1, H.B., Impacts of gut bacteria on human health and diseases, Int International Journal of Molecular Sciences, 16 (4): 7493-519, 2015.
• [30] Khanna, S., Tosh, P.K., A clinician’s primer on the role of the microbiome in human health and disease, Mayo Clinic Proceedings. Elsevier, 89(1):107-14, 2014.
• [31] Stefanaki, C., Peppa, M., Mastorakos, G., Mastorakos, G., Chrousos, G.P., Examining the gut bacteriome, virome, and mycobiome in glucose metabolism disorders: Are we on the right track? Metabolism, 73: 52-6, 2017.
• [32] Drapkina, O., Korneeva, O., Gut microbiota and obesity: Pathogenetic relationships and ways to normalize the gut microflora, Terapevticheskii Arkhiv, 88 (9): 135-42, 2016.
• [33] Boulangé, C.L., Neves, A.L., Chilloux, J., Nicholson, J.K., Dumas, M.E., Impact of the gut microbiota on inflammation, obesity, and metabolic disease, Genome Medicine, 8 (1): 42, 2016.
• [34] Turnbaugh, P.J., Hamady, M., Yatsunenko, T., Cantarel, B.L., Duncan, A., Ley, R.E., Sogin, M.L., Jones, W.J., Roe, B.A., Affourtit, J.P., Egholm, M., Henrissat, B., Heath, A.C., Knight,R., Gordon, J.I., A core gut microbiome in obese and lean twins, Nature, 457:480-4, 2009.
• [35] Million, M., Maraninchi, M., Henry, M., Armougom, F., Richet, H., Carrieri, P., Valero, R., Raccah, D., Vialettes, B., Raoult, D., Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii, International Journal of Obesity, 36:817- 25, 2012.
• [36] Duncan, S.H., Lobley, G.E., Holtrop, G., Ince, J., Johnstone, A.M., Louis, P., Flint, H.J., Human colonic microbiota associated with diet, obesity and weight loss, International Journal of Obesity, 32:1720-4, 2008.
• [37] Balamurugan, R., George, G., Kabeerdoss, J., Hepsiba, K.J., Chandragunasekaran, A.M.S., Ramakrishna, B.S., Quantitative differences in intestinal Faecalibacterium prausnitzii in obese Indian children, British Journal of Nutrition, 103:335-8, 2010.
• [38] Nadal, I., Santacruz, A., Marcos, A., Warnberg, J., Garagorri, J.M., Moreno, L.A., Matillas, M.M., Campoy, C., Martí, A., Moleres, A., Delgado, M., Veiga, O.L., Fuentes, M.G., Redondo, C.G., Sanz,Y., Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents, International Journal of Obesity, 33:758-67, 2009.
• [39] Ley, R.E., Taurnbaugh, P.J., Klein, S., Gordon, J.I., Human gut microbes associated with obesity, Nature, 444:1023, 2006.
• [40] Turnbaugh, P.J., Backhed, F., Fulton, L., Gordon, J.I., Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome, Cell Host Microbe, 3:213-23, 2008.
• [41] Kallus, S.J., Brandt L.J., The intestinal microbiota and obesity, Journal of Clinical Gastroenterology, 46:16-24, 2012.
• [42] Hooper, L.V., Wong, M.H., Thelin, A., Hansson, L., Falk, P.G., Gordon, J,I., Molecular analysis of commensal host-microbial relationships in the intestine, Science, 291:881- 4, 2001.
• [43] Armougom, F., Henry, M., Vialettes, B., Raccah, D., Raoult, D., Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and methanogens in anorexic patients, PLoS ONE, 4 (9):e 7125, 2009.
• [44] Santacruz, A., Collado, M.C., Garcia, V.L., Segura, M.T., Lagos, J.A.M., Anjos, T., Romero, M.M., Lopez, R.M., Florida, J., Campoy, C., Sanz, Y., Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women, British Journal of Nutrition, 104:83-92. 2010.
• [45] Mai, V., McCrary, Q.M., Sinha, R., Glei, M., Associations between dietary habits and body mass index with gut microbiota composition and fecal water genotoxicity: an observational study in African American and Caucasian American volunteers, Nutrition Journal, 8:49, 2009.
• [46] Arumugam, M., Rae, J., Pelletier, E., Paslier, D.L.,Yamada, T., Mende, D.R., Fernandes, G.R., Tap, J., Bruls, T., Batto, J.M., Bertalan, M., Borruel, N., Casellas, F., Fernandez, L., Gautier, L., Hansen, T., Hattori, M., Hayashi, T., Kleerebezem, M., Kurokawa, K., Leclerc, M., Levenez, F., Manichanh, C., Nielsen, H.B., Nielsen, T., Pons, N., Poulain, J., Qin, J., Ponten, T.S., Tims, S., Torrents, D., Ugarte, E., Zoetendal, E.G.,Wang, J., Guarner, F., Pedersen, O., Vos, W.M., Brunak, S., Doré, J., MetaHIT Consortium (additional members), Ehrlich, H.W.S.D., Bork, P., Enterotypes of the human gut microbiome, Nature, 473:174-80, 2011. [ 47] Schwiertz, A., Taras, D., Schafer, K., Beijer, S., Bos, N.A., Donus, C., Hardt, P.D., Microbiota and SCFA in lean and overweight healthy subjects, Obesity, 18:190-5, 2010.
• [48] Collado, M.C., Isolauri, E., Laitinen, K., Salminen, S., Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women, The American Journal of Clinical Nutrition, 88:894-9, 2008.
• [49] Lee, H.Y., Park, J.H., Seok, S.H., Baek, M.W., Kim, D.J., Lee, K.E., Paek, K.S., Lee, Y., Park, J.H., Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show antiobesity effects in diet-induced obese mice, Biochimica et Biophysica Acta, 1761:736-44, 2006.