Agricultural Science Digest

  • Chief EditorArvind kumar

  • Print ISSN 0253-150X

  • Online ISSN 0976-0547

  • NAAS Rating 5.52

  • SJR 0.176, CiteScore: 0.357

Frequency :
Bi-monthly (February, April, June, August, October and December)
Indexing Services :
BIOSIS Preview, Biological Abstracts, Elsevier (Scopus and Embase), AGRICOLA, Google Scholar, CrossRef, CAB Abstracting Journals, Chemical Abstracts, Indian Science Abstracts, EBSCO Indexing Services, Index Copernicus
Submit

Full Research Article

The Harmful Effect of a Slimming Drug Compared to a Mix of Some Plants Extract on Rats

Sara Saeb Rasheed1, Rawnaq Z. Fadhil1, Aveen R. Mohsin2, Salah M.M. Al-Chalabi1, Ferial A. Al Mahdawi3, Ahmed Flayyih Hasan1,*
  • 0009-0007-9208-5046
1Biotechnology Research Center, Al-Nahrain University, Baghdad, Iraq.
2College of Science for Women, University of Baghdad, Baghdad, Iraq.
3Department of Biology, Al-Farabi University College, Baghdad, Iraq.

ABSTRACT

Background: Xenical drug impact was used for studying losing weight by testing some physiological parameters in male rats compared to (Hatra herbs®) plants extract used for slimming.

Methods: ALT,AST,ALP,B.UREA Creatinine, lipids profile, TSH, T4 and T3 were examined. male rats separated into 3 groups: control group, a Xenical group (120 mg\kg b.wt) and a mix plants extract group (200 mg\kg b.wt).

Result: Results showed that body weight, cholesterol, triglyceride, VLDLand  LDL had a significant drop in plants extract group compared to control, whilst ALTandAST showed a substantial rise in Xenical group compared to control also a significant surge in ALP  in both treated groups compared to control . on other hand had, T3 and TSH had a significant reduced in Xenical group, while T3  showed non significant differences in plants extract group compared to control ,in the meantime T4 exhibited increased significance in Xenical group and non significant differences  in plants extract group compared to control. B.urea showed a significant escalation in Xenical group compared to plants extract group and control, while creatinine noted no significant differences in all treated groups compared to control group.

INTRODUCTION

Obesity has been described as an excessive body fat accumulation so that may elevated risk in the individual health (Woolcott et al., 2018) and it is rated that over one billion adult the world are overweight and at least one to third of this category from population are assorted as obese. A body mass index (BMI) more than 25 considered overweight and over 30 obese, therefor several factors participate to an individual’s capability to get weight like genetic predisposition, age and environmental agents. Actually the main causes of obesity are decrease exercises as well as increase intake of high energy foods (Chong et al., 2018; Drew et al., 2007), thus for obesity treating clinical therapy must be started by changing life style and focus on behavioral alternation, physical activity and diet. Weight reduction drugs or anti-obesity medication are all pharmacological agent that control or decrease weight. These drugs alter one of essential processes of individual´s body, including alters intestinal absorptionorchanging appetite. Some prescriptions of weight loss medicine are stimulants, which are recommended to use for short-term only, therefore they of limited usefulness for very obese patients, who may need to reduce weight more than months.At the end of 1998 Roche pharmaceutical firm has introduced Orlistat(Xenical) in UK and has been approved in 1999 by Food and Drug Administration (FDA) for weight-loss (Pi-Sunyer et al., 1996; Anees et al., 2024), this medicine received great attention around the world and the company assumed that it had fewer side effects, but what has been discovered later was quite the opposite. It was a new pharmacological therapy reduce fat absorption by reversibly inhibiting gastric and pancreatic lipases, these lipases have an essential role in digestion fat by breaking down the triglycerides in to absorbable free fatty acids and monoglycerides. Orlistatparticipate binds to the active sites of lipases and inactivates them so the inactivation of lipases prevents the hydrolysis of triglycerides  and thus free fatty acids are not absorbed (Nicholls et al., 2001; Humayun  et al., 2016). Xenical was supposed to be dedicated for people with a body mass index (BMI) 28 kg/m2 or 30 kg/m2 in the existing of obesity-associated complication, the usage of Xenical has been related with many mild-to-moderate gastrointestinal adverse effects (Hsieh et al., 2005). The essentially side effects of this medicine are digestion process-related, including steatorrhea (oily and soft fecal with too match flatus due to unabsorbed fats reaching toward the large intestine), incontinence and frequent gut movements and also gastrointestinal adverse state like, esophagitis and abdominal ache in few (Filippatos et al., 2008). To reduce these effects the company advises people tofollow a low-fat diet or avoidhigh fat content foods to control the oily stool and flatulenceas well as minify calorie in their meals (Ghosh et al., 2021). There are many studies showed that 8.8% of Xenical consumers stopped their treatment due to adverse events, furthermore many cases of severe liver damage had been registered (Lehmann et al., 2011) and the suggested mechanism for liver damage is hypersensitivity because only small amount of Xenical is absorbed (Nwobodo et al., 2015). At the same time several studied indicated that many of obese patients had a developed gallbladder abnormalities diagnosed by ultrasound, as well as renal abnormalities (cysts and stones) developed in other Xenical treated (Heck et al., 2000; Kang et al., 2012). On the other hand increase the risk of urea and creatinine elevation then an acute kidney damage, this occurs when the unabsorbed fat bind with calcium in the intestinal lumen resulting excessive oxalate, which eventually absorbed and deposited in kidney leading to oxalate nephropathy then increase renal stones formation (Cristina et al., 2024).
 

MATERIALS AND METHODS

Animals
 
In this experiment, 18 albino rats were used, with an average weight of 175±10, at 5-6 weeks of age, were divided into three equal groups, which they control group, treated group with 120 mg\kg of Xenical® drug, treated group with 200 mg\kg of mix plants extract (Hatra herbs®) which involved Green tea, Pimpinella (anise), Foeniculum vulgare (fennel), Coriandrum sativum( Coriander) and Carum carvi (Caraway). Animals were treated orally by gavage tube for 60 days. All rats were received diet and water ad libitum.
 
Blood and serum samples
 
At the end of the trial, rats were deprived for the whole night. Rats from each group were killed with sodium pentobarbital and then thoroughly dissected. To extract and separate the serum from the inferior vena cava, centrifugation was performed for 15 minutes at 3000 rpm. In order to analyze and estimate blood parameters, the serum was kept at -18oC.
 
Hormone assay
 
Total testosterone levels were calculated in sera using the methodology of Alankooshi et al., (2023); Alyasiri et al., (2024) whilst serum TSH and T3 and T4 levels were determined using the methods of Odell et al., (1967, 1974).
 
Biochemical analysis
 
The method of Peterson et al., (1997) was used to estimate AST, ALT, ALP and B.urea, creatinine in sera, whereas the method of Hameed (2023); Hasan et al., (2024); Hasan et al., (2023); Hameed et al., (2024) was utilized to estimate liver function and kidney function in sera, respectively.

RESULTS AND DISCUSSION

The results showed a significant decreased in body weight of group treated with Xenical and group treated with mix plants extract at the first day of experiment  compared with body weight at the end  of experiment  for both groups, while the results show a significant increase of body weight of control group at the end  of experiment (Table 1).

Table 1: Comparison between the effect of Xenical drug and mix plants extract on body weight in rats.


       
Regarding lipid profile, there was a significant decrease in cholesterol level in the treated group Xenical and group treated with mix plants extract compared with control group. The results also showed a significant decrease in the level of Triglyceride in both treated group with Xenical and mix extract respectively compared with control group. The results also obtained a significant increase in the level of HDL in group treated with Xenical)and mix extract, while the results recorded a significant decrease in LDL in group treated with Xenical and mix extract compared with control group and significant decrease in VLDL in group treated with Xenical and mix extract compared with control group.On other hand the results revealed a significant decrease in glucose level in group treated with Xenical and mix extract compared with control group (Table 2).

​

Table 2: Comparison between the effect of Xenical drug and mix plants extract on lipid profile in rats.


       
Concerning thyroid hormones, results revealed a significant decreased in T3 hormone in groups treated with Xenical drug compared with treated group with mix extract and control groups, also the results show significant increased in  T4 hormone in groups treated with Xenical drug compared with plant extract and control group. Statistical analysis showed  no  significant differences in the TSH hormone  among the three groups (Table 3).

​

Table 3: Comparison between the effect of Xenical drug and mix plants extract on thyroid hormones in rats.


       
AST enzyme level in Xenical group significantly increased  compared to the control group and mix plant group. The results also showed a significant increase in the ALT and ALP enzymes of the Xenical group compared with control and group treated with mix extract (Table 4).

​

Table 4: Comparison between the effect of Xenical drug and mix plants extract on liver function in rats.


       
B.urea had a significant rise in Xenical group compared to plants extract group and control, while creatinine recorded no significant differences in all treated groups compared to control (Table 5).       

​

Table 5: Comparison between the effect of Xenical drug and mix plants extract on kidney function.

   
       
Obesity became a worldwide pandemic which require treatment and one of the most common used drug is XinicaI. It is a well-known for its efficacy in reducing body weight through improving Metabolism then subsequently improving liver and kidney function (Humayun et al., 2016; Guerciolini et al., 1997). In this study, the body weight was decreased significantly in the treated groups in both xinical (orlistat) and natural plant extract in comparison to control (untreated) group. The main mechanism of orilstat in weight reductionthrough theinhibition of lipase a pancreatic enzyme that catalyze the hydrolysis of  lipid which prevent the absorption of lipid in intestine and eventually exerting lipid in feces (Al-Safo  et al., 2022).
       
It is well known that obesity is related to lipid abnormalities, thus the lipid profile were measured and the result indicated a significant decrease in cholesterol, triglyceride, LDL,and VLDL while a statistical  increase was shown  in HDL in both orlistat and natural plant extract with  a lower effect in natural treatment (plant extract) than the drug(orlistat), this result is due to the blocking potential of orlistat to lipase activity which led to the prevention of triglyceride breakdown and excretion of lipid. This will lower the accumulation of lipids and their break down derivative and finallycontrolling one of the main causes of obesity (Eid et al., 2023, Amin et al., 2015).
       
Decrease in glucose level was found in both treatments in contrast to control. This result proven by (Johan et al., 2022) who estimated HbA1c and fasting plasma glucose and attributed it to the mechanism of xinical which reduce lipid digestion, increase insulin sensitivity, decrease adipose tissue and increase the secretion of glucagon all of these will enhance glycemic control. They mentioned as well that xinical as thyroid hormone are routinely requested when measuring obese status (Filippatos et al., 2008). Thyroidfunction was measured and the result showed that there was no significance variation in TSH which was agreed by (Aydin et al., 2022). While, xinical showed a significant decrease inT3 compared to natural extract and control with opposite result collected in T4 hormone as a statistical elevation found only in xinical. It was found that fat accumulation is related to disturbance of thyroid hormones (high TSH and low T4) and our result elevated T4 which may be  a cause for reducing body weight (Hsieh et al., 2005, Sanyal et al., 2016). On the other hand the natural extract did not show an influence on thyroid hormone which may indicate that this material had another mechanism on metabolism.
       
Kidney function is vital for the life any defect may threat the creature life, one of the determinant of orlistatis their side effect on kidney, as the un-digest able lipid capable to bind with free calcium that should bind to oxalate in intestinal lumen, followed by elevation in oxalate absorption and finally secondary kidney damage due to accumulation of oxalate stones (Nicholls et al., 2001).
       
Liver function results showed statistical elevation in both ALT and AST enzymes in xinical in compared to control and plant extract, which may indicate a liver injury which consider an agreement with (Youssef et al., 2018) who observed liver cellular inflammation infiltration and necrosis after the treatment with orlistat.
       
The natural plant extracts including Fennel which contain multiple active components that regulates fat digestion and storage , anise oil that cause decrease in fatty acid , low densitylipoproteins and cholesterol (Ahmed et al., 2022). The green tea acts as thermo genic food and fat oxidation. Carvacrolan active compound in caraway is the main factor related to reduce body weight due to their antioxidant activity and its positive role in gut normal flora which improve digestion (Kazemipoor et al., 2013, Salih et al., 2024, Majda et al., 2022). In concern to coriander which is  rich in poly phenolic compound, these compounds was found to increase liver metabolism of cholesterol to bile acid that exerted by fesses and ameliorate obesity (Scandar et al., 2023, Al-Rubaye  et al., 2016, Abdul-Jalil  et al., 2023).The combination of these compounds may act synergistically to inhabit different enzymes to reduce body weight (Sayed et al., 2023; Yahya et al., 2024).

CONCLUSION

The above result showed that xinical had a higher anti-obesity activity than plant extract , though the side effect of xinical on liver and kidney  was higher than the natural product. This may indicate that natural extract of plant is favorable on xinical but require a longer time to work perfectly.

ACKNOWLEDGEMENT

Many thanks to all the workers in the Animal House Unit at (Biotechnology Research Center/ Al-Nahrain University) and special thanks to Professor Dr. (Salah Mehdi Mehsin Al-Chalabi) Physiology Consultant at (Biotechnology Research Center/ Al-Nahrain University).

Authors contributions
 
All authors are equally contributed in this study.
 
Ethics
 
Approval was obtained from Biotechnology Research Center/ Al-Nahrain University  of the Animal Health Care Committee under the ethical approval number (E. B. 14) dated (2.1.2023).

Funding
 
No financial support for our research.

CONFLICT OF INTEREST

The authors have not declared any conflicts of interest.

REFERENCES


  1. Abdul-Jalil, T.Z., Ibrahim, R.M., Nassir, Z.S., Extraction. (2023).  Isolation and structure elucidation of two phenolic acids from aerial parts of celery and coriander. Biomedical and Pharmacology Journal. 16(4): 2315-2332.

  2. Ahmed, A., Khateib, B., Elsharkawy, R. andElhassaneen, Y. (2022). Anti-obesity effect of some herbal mixtures (Anise, Fennel, Mint and Black seed) in a high-fat diet-Induced obese rats. Journal of Home Economics-Menofia University. 32(2): 1-18.

  3. Alankooshi, A.A., Hasan, A.F., Tousson, E., El-Atrsh, A. and Mohamed, T.M. (2023). Impact of coriander seeds extract against thyroidectomy induced testicular damage and DNA replication in male rats. OnLine J. Biol. Sci. 23(2): 193-201.

  4. Al-Rubaye, R.H.K. (2016). The inhibitory effect of aqueous extract of coriander (Coriandrum sativum L.) leaves on the activity of male reproductive system of albino mice. Iraqi Journal of Science. 57(1): 344-351.

  5. Al-Safo, Alya A. and Liqaa H. Al-Dulaimi. (2022). Effect of orlistat and aquatic extract of Rosmarinusofficinalis leaves in histopathological changes in kidney of albino rat. Iraqi Journal of Veterinary Sciences. 36(2): 393-400.

  6. Alyasiri, T., Hameed, H.M. and Hasan, A.F. (2024). The effects of bisphenol A of polycarbonate plastics on various blood and fertility parameters, along with histological changes in male albino rats. Asian Journal of Dairy and Food Research.  1-7. doi: 10.18805/ajdfr.DRF-435.

  7. Amin, H.M., Nagy S. Tawfek, B.K. Abo-El H. and Marwa S. Abd El-Ghany. (2015). Anti-Obesity potential of orlistat and amphetamine in rats fed on high fat diet. Sciences. 5(2): 453-461.

  8. Anees, S., Manzoor, I., Fatima, K., Hamid, R. and Ganie, S.A. (2024). GC-MS analysis and potential therapeutic efficacy of extracts from Allium humile Kunth in lowering dyslipidemia in wistar rat models. Journal of Ethnopharmacology. 320: 117478.

  9. Aydin, B. (2022). Does Orlistat Affect Levothyroxine Bioavailability?. Eurasian Journal of Medical Investigation. 6(1): 22-27.

  10. Chong E.T.J., Lee P.C. (2018). Prevalence of overweight and obesity in malaysia, 2010-2016: A comprehensive meta-analysis.  Southeast Asian J. Trop. Med. Public Health. 49: 859-869. 

  11. Cristina, R.T., Mohamed, E.A., Tulcan, C., Dumitrescu, E., Muselin, F., Orã’an, S. A. and Vlad, D. (2024). The oxidative stress markers’ protective influence of sea buckthorn and grape extracts in atorvastatin-treated hyperlipidemic rats. Nutrients. 16(12): 1954.

  12. Drew, B., A. Dixon, J. Dixon. (2007). Obesity management, update on orlistat, Vasc Health Risk Manag. 3: 817-821.

  13. Eid, A.M., Linda, I., Karmah, K., Omran, H., Hla, S. and Sally, A.A. (2023). Comparing and contrasting different herbal products intended for the management of obesity approved in the Palestinian markets. BMC Complementary Medicine and Therapies. 23: 1-3.

  14. Filippatos, T.D., Derdemezis, C.S., Gazi, I.F., Nakou, E.S., Mikhailidis, D.P., Elisaf, M.S. et al. (2008). Orlistat-associated adverse effects and drug interactions: A critical review. Drug Saf.  31: 53-65.

  15. Filippatos, T.D., Christos, S. Derdemezis, I.F. Gazi, E.S. Nakou, D.P. Mikhailidis and Moses, S.E. (2008). Orlistat-associated adverse effects and drug interactions: A critical review. Drug safety. 31: 53-65.

  16. Ghosh, S., Bornman, C. and Zafer, M.M. (2021). Antimicrobial resistance threats in the emerging COVID-19 pandemic: Where do we stand?. Journal of infection and public health. 14(5): 555-560.

  17. Guerciolini, R. (1997). Mode of action of orlistat. International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity 21(3): S12-23.

  18. Hameed, H.M., Hasan, A.F., Razooki, Z.H., Tousson, E. and Fatoh, S.A. (2023). Orlistat induce renal toxicity, DNA damage and apoptosis in normal and obese female rats. OnLine Journal of Biological Sciences. 23(1): 25-32. https://doi.org/ 10.3844/ojbsci.2023.25.32.

  19. Hameed, H.M., Razooki, Z.H., Hasan, A.F., Rasool, A.A.A.A. and Abed, I.J. (2024). Therapeutic effect of essential oils (Citrus sinensis) against ehrlich ascites model induced renal toxicity in female mice. Agricultural Science Digest. doi: 10.18805/ag.DF-632.

  20. Hasan, A.F., Alankooshi, A.A., Abbood, A.S., Dulimi, A.G., Mohammed Al-Khuzaay, H., Elsaedy, E.A. and Tousson, E. (2023). Impact of B-Glucan against ehrlich ascites carcinoma induced renal toxicity in mice. OnLine Journal of Biological Sciences. 23(1): 103-108. https://doi.org/10.3844/ ojbsci.2023.103.108.

  21. Hasan, A.F., Hameed, H.M., Hadid, M.A. and Tousson, E. (2024). Impact of chia (Salvia hispanica) seeds extract on ehrlich ascites model induced kidney toxicity in female mice. Asian Journal of Dairy and Food Research. 43(4): 750-756. doi: 10.18805/ajdfr.DRF-397.

  22. Heck, A., J. Yanovski, K. Calis, 2000. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 20: 270-279.

  23. Hsieh, C.J., P-W. Wang, R.T. Liu, S.C. Tung, W.Y. Chien, J.F. Chen, C.H. Chen, M.C. Kuo and Y.H. Hu. (2005). Orlistat for obesity: Benefits beyond weight loss. Diab. Res. Clin. Prac. 67: 78-83.

  24. Humayun, Y., Ball, K.C., Lewin, J.R., Lerant, A.A., Fülöp, T. (2016). Acute oxalate nephropathy associated with orlistat. J. Nephropathol. Apr. 5(2): 79-83. 

  25. Johan, A.R.D., Linda D., Anandia, N.P., Benny I.P., Chabib, F.A., Maria, M.D.H. and Triana, N. (2022). The effect of orlistat administration in change of glycemic control and weight loss of obesity or overweight patients with type 2 diabetes mellitus. Folia MedicaIndonesiana. 58(1): 74-79.

  26. Kang, J.G., Park, C.Y. (2012). Anti-obesity drugs: A review about their effects and safety. Diabetes Metab J. 36: 13-25.

  27. Kazemipoor, M., Hajifaraji, M., Haerian, B.S., Mosaddegh, M.H. and Cordell, G.A. (2013). Antiobesity effect of caraway extract on overweight and obese women: A randomized, triple-blind, placebo-controlled clinical trial. Evidence-based Complementary and Alternative Medicine. 2013.

  28. Lehmann, J. (2011). How the media framed weight-loss drugs: A content analysis of newspaper coverage of prescription and over-the-counter Weight-loss Drugs. Arizona State University. 

  29. Majda, B., Barchan, A., Aarab, A., Bakkali, M., Arakrak, A. and Laglaoui, A. (2022). Evaluation of the antibacterial activity of essential oils against e. coli isolated from rabbits. Iraqi Journal of Agricultural Sciences. 53(4): 802-809.

  30. Nicholls, H. (2001). Roche reveals benefits of Xenical for type 2 diabetics. Tren. Endocriol. Met. 12: 381.

  31. Nwobodo, N.N. (2015). Toxicity and safety concerns in orlistat therapy for obesity. A critical evaluation. Asian J. Biomed Pharm Sci. 5: 1-4.

  32. Peterson, E.D., Shaw, L.K., DeLong, E.R., Pryor, D.B., Califf, R.M. and Mark, D.B. (1997). Racial variation in the use of coronary- revascularization procedures-are the differences real? Do they matter?. New England Journal of Medicine. 336(7): 480-486.

  33. Pi- Sunyer, F.X. (1996). A review of long-term studies evaluating the efficacy of weight loss in ameliorating disorders associated with obesity. Clin. Ther. 18: 1006-1035.

  34. Salih, H.H. (2024). Biosynthesis of silver nanoparticles by using green tea (Camellia sinensis) extracts. Baghdad Science Journal. 21(5): 1470-1470.

  35. Sanyal, D. and Moutusi, R. (2016). Hypothyroidism and obesity: An intriguing link. Indian Journal of Endocrinology and Metabolism. 20(4): 554.

  36. Sayed, U.F.S.M., Moshawih, S., Goh, H.P., Kifli, N., Gupta, G., Singh, S.K. and Goh, B.H. (2023). Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management. Frontiers in Pharmacology. 14.

  37. Scandar, S., Zadra, C. andMarcotullio, M.C. (2023). Coriander (Coriandrum sativum) polyphenols and their nutraceutical value against obesity and metabolic syndrome. Molecules. 28(10): 4187.

  38. Woolcott O.O., Seuring T. (2022). Prevalence trends in obesity defined by the relative fat mass (RFM) index among adults in the United States: 1999-2018. MetabClin Exp. 128. doi: 10. 1016/J.METABOL.2021.155027.

  39. Yahya, A., Adil, Obaid, W., Mohammed Hameed, O. and Hasan, A.F. (2024). Histopathological and immunohistochemical studies on the effects of silver oxide nanoparticles (AgNPs) on male rats’ liver. Journal of Bioscience and Applied Research. 10(3): 392-398.

  40. Youssef, S. (2018). Light and electron microscopic study of the effect of orlistat on the liver of adult male albino rats and the possible protective role of â-carotene. Forensic Medicine and Anatomy Research. 6(2): 20-36.
Reviewed By

Download Article
In this Article
    Contact us
    Follow us

    Editorial Board

    View all (0)