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Abstract

Environmental contamination by chemical agents has been on the increase with pesticides being major contributors to the process. Exposure to pesticides such as Cypermethrin and Dichlorvos has raised concerns regarding their potential adverse effects on oxidative status in biological tissues. Studies have shown that even at low doses, these toxicants still elicit some toxic effects. 36 Male wistar rats weighing between 100 and 120g were purchased and acclimatized for 2 weeks in plastic cages in the animal house. The animals were fed and given water ad libitum. They were randomly assigned into different treatment groups; Control, Cypermethrin and Dichlorvos. The pesticides were administered at their referenced No Observed Adverse Effect Levels (NOAELs). The animals were sacrificed after administration of the pesticides for 30 days and their blood collected through cardiac puncture to be used in carrying out biochemical assays. Results obtained revealed significant elevations in the levels of Inflammatory Cytokines (Interleukin 1Beta, Interleukin 6 and Tumor Necrosis Factor Alpha). Further evaluation revealed significant alterations of the redox status of the rats administered with the toxicants as compared with the control. Our findings suggests that administration of Cypermethrin and Dichlorvos distorted the levels of the inflammatory markers assessed in the rats and as well was able to induce oxidative balance of the animals.

Keywords

Cypermethrin, Dichlorvos, Inflammatory, Cytokines, Oxidative

Introduction

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Pollution is a global issue, and the consequences for human health are concerning.  Pesticides are chemicals that are commonly employed in the agricultural business to kill pests that have the potential to harm crops.   Pesticides can be classed according to their target and chemical composition.   Pesticides are classified according to their chemical composition. Commonly used pesticides include chlorpyrifos (organophosphate), cypermethrin (pyrethroid group) and carbofuran (carbamate group) [1]. The usage of chlorpyrifos is widespread, with 60% in the United States and 53% in China [2]. In addition to chlorpyrifos, carbofuran is commonly utilized, particularly because organochlorines are forbidden, making carbofuran an alternative [3].   Cypermethrin is a common pyrethroid insecticide, as evidenced by the fact that more than half of farmers in Bostwana, Africa, use it.  Pesticides can eliminate pests, but they can also be hazardous to humans if exposed.   Inhalation, cutaneous contact, and ingestion are all methods by which substances enter the human body.  Dietary exposures are also the most common source of toxicant exposure outside of the workplace. Calls have also been made on the need for a more comprehensive understanding of the impact of toxicants on immune responses, particularly at sub-adverse levels [4]. Evidence has shown that some chemicals, especially endocrine disrupting compounds, can exert toxicological effects even at extremely low doses. There have also been calls to review exposure limits of these chemicals, hence necessitating this research work. This research holds significance in shedding light on the potential health risks associated with chronic exposure to seemingly innocuous levels of toxicants. By unraveling the effects on oxidative and inflammatory markers, the findings may inform public health policies, refine environmental regulations, and guide the development of targeted therapeutic strategies to mitigate the subtle yet impactful consequences of environmental toxicant exposure. Pesticides are a group of chemicals as well as microbes (such as viruses) used to eradicate weeds, insects, bacteria and fungus [5]. Pesticides are classified into families such as organophosphates, carbamates, organochlorines, pyrethroids, triazoles, bipyridyl herbicides, triazine herbicides and chloroacetanilide herbicides [6]. Yearly, around 2 million tons of pesticides are used worldwide with the Chinese, Americans and Argentines being the leading producers [7]. Demand for agricultural products like pesticides has increased due to increase in world population [8]. World Health Organization yearly estimates for pesticides poisoning are in the range of about 3 million in underdeveloped countries with roughly 18,000 deaths [9]. Widespread pesticides’ use for various purposes (e.g., industrial, commercial, and individual households) around the world demonstrates the importance of these chemicals but the negative impacts on the environment, wildlife, and human health are not well elucidated [10]. Individual pesticides’ use agriculturally, residentially or occupationally gives rise to high risk of direct exposure. Larger populations might however be exposed indirectly to pesticides and their breakdown products at low levels through, air, dust, food and water [11]. Pollution of surface waters due to pesticides’ usage has been widely reported globally and is a major issue that raises concerns at the local, regional, national, and international levels [12]. Given that these indirect exposure routes include low quantities of pesticide, long-term exposure to them may be hazardous to humans [11]. It would appear pesticides seem to have no long-term adverse effects on adult humans at modest dosages of exposure [13]
Pesticide poisoning occurs in people who live near pesticide-treated fields, as well as agricultural personnel who come into contact directly with pest control agents [14] Further epidemiological studies revealed that pesticides’ exposures at high levels are correlated with increased risk of chronic diseases such as diabetes mellitus, cancer, cardiotoxicity, Parkinson's disease, birth defects, neurological defects, and reproductive disorders [15].

MATERIALS AND METHODS

Study site: the study was carried out at the Biochemistry department, Ladoke Akintola University of Technology, Ogbomoso.

Experimental Design

36 Male wistar rats weighing between 100 and 120g were purchased and acclimatized for 2 weeks in plastic cages in the animal house. The animals were fed and given water ad libitum. They were randomly assigned to different treatment groups, each corresponding to a specific toxicant.

Rat Grouping

The rats were grouped into three (3) with each group containing twelve (12) rats based on the pesticide to be administered including the control group as illustrated below

Table 1: Rat grouping

Group

Pesticide Administration

A

Control

B

Dichlorvos

C

Cypermethrin

Biochemical analysis

Anthropometric Parameters, Inflammatory markers (Interleukin 1beta, Interleukin 6, TNF alpha) as well as Oxidative stress markers (SOD, MDA, AOPP, FRAP, Catalase) was carried out.

Statistical Analysis

The results obtained from the study are presented as the mean ± SD. Statistical analysis between control and pesticide groups was done using one-way analysis of variance (ANOVA) and Tukey’s post-hoc test. GraphPad Prism would be employed for data analysis. Values of p ≤ 0.05 are regarded as statistically significant

RESULTS

Table 1 below presents results of inflammatory cytokines evaluation of rats administered with Dichlorvos and Cypermethrin

 

Control

Dichlorvos

Cypermethrin

IL-1B

48.54± 1.26

48.72± 1.38

52.83± 1.09a

IL-6

36.11± 1.14

39.41± 0.70a

36.46± 1.57

TNF-Alpha

41.09± 0.62

54.95± 0.71a

51.31± 0.66a

Table 1 Evaluation of effects of administration of Dichlorvos and Cypermethrin on inflammatory cytokines in male Wistar rats. Data are expressed as means± S.D. of twelve animals per group. Values in the same row with superscript a are significantly different (p < 0.05) from the control Results obtained from the evaluation of Interleukin 1B revealed significant elevation of the inflammatory cytokine in the cypermethrin administered group as compared with the control. Evaluation of the interleukin 6 on administration of the pesticides revealed that the Dichlorvos administered group had elevated levels of the inflammatory cytokine. Assessment of the rats after administration of the toxicants revealed that the Tumor Necrosis Factor Alpha was significantly upregulated in both the Dichlorvos and Cypermethrin administered groups as compared with the control group.

 

Control

Dichlorvos

Cypermethrin

AOPP

6.04± 0.61

4.51± 0.50a

5.45± 0.31a

FRAP

7.27± 0.42

8.08± 0.77a

7.84± 0.92

SOD

45.64± 0.98

48.92± 0.65a

46.14± 0.75

Catalase

43.22± 0.92

40.22± 0.55a

38.29± 0.53a

MDA

25.73± 0.59

34.88± 0.46a

34.79± 0.35a

Table 2 Evaluation of effects of administration of Dichlorvos and Cypermethrin on oxidative stress markers in male Wistar rats. Data are expressed as means± S.D. of twelve animals per group. Values in the same row with superscript a are significantly different (p < 0.05) from the control. Results obtained from the evaluation of the oxidative stress markers revealed that administration of Dichlorvos and Cypermethrin significantly reduced the Advanced Oxidation Protein Products (AOPP) in the experimental animals. The Ferric Reducing Antioxidant Potential (FRAP) assessment revealed that administration of Dichlorvos significantly elevated the antioxidant capacity of the rats. Assessment of the Superoxide Dismutase activity revealed that similar to what obtained with FRAP, only the Dichlorvos administered group was significantly elevated as compared with the control group. Evaluation of the Catalase activity revealed that administration of both Dichlorvos and Cypermethrin significantly downregulated the enzyme activity. Evaluation of the malondialdehyde (MDA) concentration revealed that administration of the toxicants led to significant increase in MDA concentration as compared with the control group.

DISCUSSION

Pesticides are widely used in agriculture to control insect pests but have been found to have toxic effects on various physiological systems. Upon ingestion, toxicants are transported by the blood to various organs including the liver and kidney where they may eventually cause harmful effects. Blood can act as an important indicator of animal health [16]. Several studies have demonstrated that administration of pesticides either singly or in combination could elicit inflammatory responses via the activation of pro-inflammatory cytokines such as on interleukin 1β, interleukin 6 as well TNF α [17,18,19] Evaluation of the effects of the pesticides on interleukin 1β levels in the animals indicated that the cypermethrin administered group had elevated levels as compared with the control and the dichlorvos administered group, similar with a study by [18]. The results obtained portends that administration of the pesticides might have led to an inflammatory response. This is consistent with previous studies reporting that administration of pesticides could cause inflammation (20,21,17). Assessment of the interleukin 6 levels in the animals after 30 days of administration revealed that administration of the pesticides led to elevated levels of the inflammatory cytokines in both pesticides’ administered groups as compared with the control, although only the Dichlorvos administered group was of significance. These elevations is consistent with the results obtained from interleukin 1Beta evaluation earlier reported in this study. Evaluation of the TNF-α levels in the animals after 30 days of exposure to the pesticides revealed elevated levels as compared to the control which is in agreement with previous studies [22,23] indicating that administration of toxicants could elicit inflammatory responses. Studies have associated pesticide accumulation with increased oxidative stress and production of ROS [18]. Pyrethroids induced cellular oxidative damage and accumulation of peroxidation products have been reported in literature [18]. These oxidative products have been extensively used as markers of oxidative stress. In the present study, pesticides’ exposures generated significant oxidative stress in the animals as evidenced by significant alterations of the lipid peroxidation and protein oxidation products, namely MDA and AOPP. Altered AOPP concentrations in the rats are also a pointer to the degree of damage done by the pesticides on the tissue protein components. These results further aligns with earlier reports implying the ability of pesticides to cause oxidative stress. [18]

ACKNOWLEDGEMENTS

The authors would like to appreciate the Federal Government of Nigeria’s Tertiary Education Trust Fund for it’s support towards this research.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest whatsoever.                                        

REFERENCE

  1. Kaur, R., Mavi, G. K., and Raghav S. (2019). Pesticides Classification and its Impact on Environment. Int.J.Curr.Microbiol.App.Sci. 8(3): 1889-1897
  2. Foong, S. Y., Ma, N. L., Lam, S. S., Peng, W., Low, F., Lee, B. H., Alstrup, A. K., & Sonne, C. (2020). A recent global review of hazardous chlorpyrifos pesticide in fruit and vegetables: Prevalence, remediation and actions needed. Journal of Hazardous Materials, 400, 123006. https://doi.org/10.1016/j.jhazmat.2020.123006
  3. Indraningsih (2008). Effect of carbamate insecticide use on animal health and its products. Jurnal Wartazoa 18: 101-114
  4. Miossec, P., & Kolls, J. K. (2012). "Targeting IL-17 and TH17 cells in chronic inflammation." Nature Reviews Drug Discovery, 11(10), 763–776.
  5. Jayaraj, R., Megha, P., & Sreedev, P. (2016). Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment. Interdisciplinary toxicology, 9(3-4), 90–100. https://doi.org/10.1515/intox-2016-0012
  6. Georgiadis, N., Konstantinos T, Christina T., Alexandros V., Ramin R., Ioannis G., Aristides T., Dimitrios S., Demetrios K. (2018), Pesticides and cardiotoxicity. Where do we stand? Toxicology and Applied Pharmacology, Volume 353, 1-14.
  7. Sharma, A., Kumar, V., Shahzad, B., Tanveer, M., Sidhu, G.P.S., Handa, N., Kohli, S.K., Yadav, P.,Bali, A.S.,Parihar, R.D.,Dar, O.I.,Singh, K.,Jasrotia, S.,Bakshi, P., Ramakrishnan, M.,Kumar, S.,Bhardwaj, R.,Thukral, A.K. (2019). Worldwide pesticide usage and its impacts on ecosystem (Review) SN Applied Sciences Volume 1, Issue 11, November 2019, Article number 1446
  8. Medithi, S., Kasa, Y., Jee, B., Kodali, V., Jonnalagadda, P. (2020). Organophosphate pesticide exposure among farm women and children: Status of micronutrients, acetylcholinesterase activity, and oxidative stress. Archives of Environmental and Occupational Health. 77. 10.1080/19338244.2020.1854646.
  9. Min J., Han J. and Kim K. (2017). Human cholestatic hepatitis owing to polyoxyethylene nonylphenol ingestion. Medicine. 96(32): e7737
  10. Damalas, C.A. and Eleftherohorinos, I.G. (2011) Pesticide Exposure, Safety Issues, and Risk Assessment Indicators. International Journal of Environmental Research and Public Health, 8, 1402-1419.http://dx.doi.org/10.3390/ijerph8051402
  11. Wani, A.A., Dar, A.A., Ishrat, J, Khurshid A., Javid, A.S., and Irshad H. D. Method validation and simultaneous quantification of eight organochlorines/organophosphates in apple by gas chromatography J Sci Food Agric 2019; 99: 3687–3692
  12. Sule, R. O., Condon, L., & Gomes, A. V. (2022). A Common Feature of Pesticides: Oxidative Stress—The Role of Oxidative Stress in Pesticide-Induced Toxicity. Oxidative Medicine and Cellular Longevity, 2022(1), 5563759. https://doi.org/10.1155/2022/5563759
  13. Gangemi, S., Edoardo M, Michele T, Giusi B, De Luca, A., Carmela A, Irene P, Massimo L. (2016). Occupational exposure to pesticides as a possible risk factor for the development of chronic diseases in humans. Molecular Medicine Reports, DOI 10.3892/mmr.2016.5817 Pubmed ID 27748877
  14. Coronado, G. D., Holte, S., Vigoren, E., Griffith, W. C., Barr, D. B., Faustman, E., & Thompson, B. (2011). Organophosphate Pesticide Exposure and Residential Proximity to Nearby Fields: Evidence for the Drift Pathway on JSTOR. Journal of Occupational and Environmental Medicine, 884. https://doi.org/45009874
  15. Kori, R. K., Singh, M. K., Jain, A. K., & Yadav, R. S. (2018). Neurochemical and Behavioral Dysfunctions in Pesticide Exposed Farm Workers: A Clinical Outcome. Indian Journal of Clinical Biochemistry, 33(4), 372. https://doi.org/10.1007/s12291-018-0791-5
  16. Jorum O.H., Piero N.M. and Machocho A.K. (2016) Haematological Effects of Dichloromethane-Methanolic Leaf Extracts of Carissa edulis (Forssk.) Vahl in Normal Rat Models. Journal of Hematological. Thromboembolic Diseases. 4:232.
  17. Lopes-Ferreira, M.; Farinha, L.R.L.; Costa, Y.S.O.; Pinto, F.J.; Disner, G.R.; da Rosa, J.G.d.S. and Lima, C. (2023). Pesticide-Induced Inflammation at a Glance. Toxics, 11: 896.
  18. Afolabi, O.K., Oyewo, E.B., Adeleke G.E., Badmus, J.A. and Wusu, A.D. (2019). Mitigation of Aluminium Phosphide-induced Hematotoxicity and Ovarian Oxidative Damage in Wistar Rats by Hesperidin. American Journal of Biochemistry. 9(1): 7-16
  19. Khan, D. A., Bhatti, M. M., Khan, A.F., Naqvi, S. T. (2008). Evaluation Of Pesticides Induced Toxicity By Oxidative Stress And Inflammatory Biomarkers.  Pakistan Armed Forces Medical Journal; 58(4): 380-386
  20. An, G., Park, J., Lim,W., and Song, G.(2022). Thiobencarb Induces Phenotypic Abnormalities, Apoptosis, and Cardiovascular Toxicity in Zebrafish Embryos through Oxidative Stress and Inflammation. Comprehensive Biochemical Physiology Part C Toxicological. Pharmacology. 261, 109440.
  21. Thota, S., Begum, R., Kaur, G., Bagam, P., Dorsey, W,.and Batra, S. (2022) Pentachlorophenol Mediated Regulation of DAMPs and Inflammation: In Vitro Study. Toxicol. Vitr., 83: 105378
  22. Soliman, M.M., Attia, H.F., and El-Ella, G.A.A. (2015) Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: protection by sesame oil, Int. J. Immunopathol. Pharmacol. 28 508–520.
  23. Forrester, S.J., Kikuchi, D.S., Hernandes, Xu, M.S., Q. and Griendling, K.K., (2018). Reactive oxygen species in metabolic and inflammatory signaling, Circ. Res. 122: 877–902.

Reference

  1. Kaur, R., Mavi, G. K., and Raghav S. (2019). Pesticides Classification and its Impact on Environment. Int.J.Curr.Microbiol.App.Sci. 8(3): 1889-1897
  2. Foong, S. Y., Ma, N. L., Lam, S. S., Peng, W., Low, F., Lee, B. H., Alstrup, A. K., & Sonne, C. (2020). A recent global review of hazardous chlorpyrifos pesticide in fruit and vegetables: Prevalence, remediation and actions needed. Journal of Hazardous Materials, 400, 123006. https://doi.org/10.1016/j.jhazmat.2020.123006
  3. Indraningsih (2008). Effect of carbamate insecticide use on animal health and its products. Jurnal Wartazoa 18: 101-114
  4. Miossec, P., & Kolls, J. K. (2012). "Targeting IL-17 and TH17 cells in chronic inflammation." Nature Reviews Drug Discovery, 11(10), 763–776.
  5. Jayaraj, R., Megha, P., & Sreedev, P. (2016). Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment. Interdisciplinary toxicology, 9(3-4), 90–100. https://doi.org/10.1515/intox-2016-0012
  6. Georgiadis, N., Konstantinos T, Christina T., Alexandros V., Ramin R., Ioannis G., Aristides T., Dimitrios S., Demetrios K. (2018), Pesticides and cardiotoxicity. Where do we stand? Toxicology and Applied Pharmacology, Volume 353, 1-14.
  7. Sharma, A., Kumar, V., Shahzad, B., Tanveer, M., Sidhu, G.P.S., Handa, N., Kohli, S.K., Yadav, P.,Bali, A.S.,Parihar, R.D.,Dar, O.I.,Singh, K.,Jasrotia, S.,Bakshi, P., Ramakrishnan, M.,Kumar, S.,Bhardwaj, R.,Thukral, A.K. (2019). Worldwide pesticide usage and its impacts on ecosystem (Review) SN Applied Sciences Volume 1, Issue 11, November 2019, Article number 1446
  8. Medithi, S., Kasa, Y., Jee, B., Kodali, V., Jonnalagadda, P. (2020). Organophosphate pesticide exposure among farm women and children: Status of micronutrients, acetylcholinesterase activity, and oxidative stress. Archives of Environmental and Occupational Health. 77. 10.1080/19338244.2020.1854646.
  9. Min J., Han J. and Kim K. (2017). Human cholestatic hepatitis owing to polyoxyethylene nonylphenol ingestion. Medicine. 96(32): e7737
  10. Damalas, C.A. and Eleftherohorinos, I.G. (2011) Pesticide Exposure, Safety Issues, and Risk Assessment Indicators. International Journal of Environmental Research and Public Health, 8, 1402-1419.http://dx.doi.org/10.3390/ijerph8051402
  11. Wani, A.A., Dar, A.A., Ishrat, J, Khurshid A., Javid, A.S., and Irshad H. D. Method validation and simultaneous quantification of eight organochlorines/organophosphates in apple by gas chromatography J Sci Food Agric 2019; 99: 3687–3692
  12. Sule, R. O., Condon, L., & Gomes, A. V. (2022). A Common Feature of Pesticides: Oxidative Stress—The Role of Oxidative Stress in Pesticide-Induced Toxicity. Oxidative Medicine and Cellular Longevity, 2022(1), 5563759. https://doi.org/10.1155/2022/5563759
  13. Gangemi, S., Edoardo M, Michele T, Giusi B, De Luca, A., Carmela A, Irene P, Massimo L. (2016). Occupational exposure to pesticides as a possible risk factor for the development of chronic diseases in humans. Molecular Medicine Reports, DOI 10.3892/mmr.2016.5817 Pubmed ID 27748877
  14. Coronado, G. D., Holte, S., Vigoren, E., Griffith, W. C., Barr, D. B., Faustman, E., & Thompson, B. (2011). Organophosphate Pesticide Exposure and Residential Proximity to Nearby Fields: Evidence for the Drift Pathway on JSTOR. Journal of Occupational and Environmental Medicine, 884. https://doi.org/45009874
  15. Kori, R. K., Singh, M. K., Jain, A. K., & Yadav, R. S. (2018). Neurochemical and Behavioral Dysfunctions in Pesticide Exposed Farm Workers: A Clinical Outcome. Indian Journal of Clinical Biochemistry, 33(4), 372. https://doi.org/10.1007/s12291-018-0791-5
  16. Jorum O.H., Piero N.M. and Machocho A.K. (2016) Haematological Effects of Dichloromethane-Methanolic Leaf Extracts of Carissa edulis (Forssk.) Vahl in Normal Rat Models. Journal of Hematological. Thromboembolic Diseases. 4:232.
  17. Lopes-Ferreira, M.; Farinha, L.R.L.; Costa, Y.S.O.; Pinto, F.J.; Disner, G.R.; da Rosa, J.G.d.S. and Lima, C. (2023). Pesticide-Induced Inflammation at a Glance. Toxics, 11: 896.
  18. Afolabi, O.K., Oyewo, E.B., Adeleke G.E., Badmus, J.A. and Wusu, A.D. (2019). Mitigation of Aluminium Phosphide-induced Hematotoxicity and Ovarian Oxidative Damage in Wistar Rats by Hesperidin. American Journal of Biochemistry. 9(1): 7-16
  19. Khan, D. A., Bhatti, M. M., Khan, A.F., Naqvi, S. T. (2008). Evaluation Of Pesticides Induced Toxicity By Oxidative Stress And Inflammatory Biomarkers.  Pakistan Armed Forces Medical Journal; 58(4): 380-386
  20. An, G., Park, J., Lim,W., and Song, G.(2022). Thiobencarb Induces Phenotypic Abnormalities, Apoptosis, and Cardiovascular Toxicity in Zebrafish Embryos through Oxidative Stress and Inflammation. Comprehensive Biochemical Physiology Part C Toxicological. Pharmacology. 261, 109440.
  21. Thota, S., Begum, R., Kaur, G., Bagam, P., Dorsey, W,.and Batra, S. (2022) Pentachlorophenol Mediated Regulation of DAMPs and Inflammation: In Vitro Study. Toxicol. Vitr., 83: 105378
  22. Soliman, M.M., Attia, H.F., and El-Ella, G.A.A. (2015) Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: protection by sesame oil, Int. J. Immunopathol. Pharmacol. 28 508–520.
  23. Forrester, S.J., Kikuchi, D.S., Hernandes, Xu, M.S., Q. and Griendling, K.K., (2018). Reactive oxygen species in metabolic and inflammatory signaling, Circ. Res. 122: 877–902.

Photo
Akinyele Abdulmuiz Akindamola
Corresponding author

Department of Science Laboratory Technology, Federal Polytechnic Ayede, Oyo State

Photo
Afolabi Olusegun Kayode
Co-author

Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State

Photo
Adedeji Adebayo Lawrence
Co-author

Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State

Photo
Okesanjo Abdulazeem Korede
Co-author

Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State

Akinyele Abdulmuiz Akindamola*, Afolabi Olusegun Kayode, Adedeji Adebayo Lawrence, Okesanjo Abdulazeem Korede, Evaluation of Chronic Low-Level Exposure to Cypermethrin and Dichlorvos on Oxidative Indices and Inflammatory Cytokines in Male Wistar Rats, Int. J. Sci. R. Tech., 2026, 3 (3), 123-127. https://doi.org/10.5281/zenodo.18927137

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