| تعداد نشریات | 126 |
| تعداد شمارهها | 7,094 |
| تعداد مقالات | 76,237 |
| تعداد مشاهده مقاله | 151,692,358 |
| تعداد دریافت فایل اصل مقاله | 113,798,395 |
Ferulic Acid and Submandibular Salivary Gland in Rats Exposed to Methotrexate | ||
| Iranian Journal of Veterinary Medicine | ||
| مقاله 12، دوره 20، شماره 2، خرداد و تیر 2026، صفحه 329-338 اصل مقاله (3.16 M) | ||
| نوع مقاله: Original Articles | ||
| شناسه دیجیتال (DOI): 10.32598/ijvm.20.2.1005829 | ||
| نویسندگان | ||
| Maha Talal Fattah؛ Rana Khairi Attarbashee* ؛ Faehaa Azher Al-Mashhadane | ||
| Department of Dental Basic Sciences, College of Dentistry, University of Mosul, Mosul, Iraq. | ||
| چکیده | ||
| Background: Widely used in chemotherapy, methotrexate (MTX) is known to induce oxidative stress and cell death in non-target organs, such as salivary glands. Objectives: This study investigates the preventive and therapeutic effects of ferulic acid (FA), a naturally occurring antioxidant and anti-inflammatory compound, on the histological and biochemical alterations induced by MTX in the submandibular salivary glands of rats. Methods: A total of 24 mature male rats were divided into 4 groups (6 rats in each group): Group I (control) received a normal saline solution for 18 days during the study. On the 15th day of the study, group II (MTX-treated) rats got a single intraperitoneal (IP) injection of MTX (40 mg/kg). They were left untreated for three days. Group III was the protective group (FA+MTX). The rats were given FA (60 mg/kg/d, orally) for 14 days before receiving a single IP injection of MTX (40 mg/kg) on day 15. Group IV was the therapeutic group (MTX+FA). After three days of MTX administration (days 15, 16, and 17), they received FA (60 mg/kg/day, orally). Results: FA significantly attenuated MTX-induced biochemical and histological anomalies, as demonstrated by decreased levels of IL-1β and caspase 3, elevated levels of IL-10, and attenuated degenerative alterations in the granular convoluted tubule, mucous acini, and striate duct. Conclusion: The study revealed that MTX induces inflammation and cellular death in the submandibular salivary glands of rats, as evidenced by increased levels of IL-1β and caspase 3, along with decreased levels of IL-10, thereby impairing tissue architecture. FA, given either prophylactically or therapeutically, significantly reduced inflammation and apoptosis. | ||
| کلیدواژهها | ||
| Apoptosis؛ Ferulic acid (FA)؛ Inflammation؛ Methotrexate (MTX)؛ Submandibular gland | ||
| اصل مقاله | ||
|
Introduction
Hematoxylin and eosin (H&E)-stained sections revealed well-organized mucous acini, granular convoluted tubules, and striated ducts without evidence of structural disruption or inflammatory changes. In contrast, Figure 4 shows the submandibular gland morphology in the MTX-treated group, characterized by extensive necrosis of mucous acinar cells and granular convoluted tubules, inflammatory cell infiltration, and marked vascular congestion, indicating severe tissue damage and inflammation resulting from MTX toxicity.
Figure 5 represents histological sections from the FA + MTX protective group, in which the salivary glands exhibit largely preserved mucous acini, with only mild necrosis and degeneration in the granular convoluted tubules.
Some vascular congestion remains evident, suggesting partial but significant protection against MTX-induced tissue injury by FA. Figure 6 shows the histological appearance of the MTX+FA therapeutic group, in which the glandular architecture is well preserved and closely resembles that of the control group.
The mucous acini, granular convoluted tubules, and striated ducts show no evident necrosis, and there is no inflammatory infiltration, indicating effective post-exposure recovery facilitated by FA. | ||
| مراجع | ||
|
Ahmed, A. A., & Mammdoh, J. K. (2022). Expression of Ki67 in submandibular salivary glands of rabbits after BTX injection: histological and immunohistochemical study. Iraqi Journal of Veterinary Sciences, 36(3), 611-620. [DOI: 10.33899/ijvs.2021.131101.1919]
Al-Allaf, L. I., Attarbashee, R. K., & Mammdoh, J. K. (2022). The effect of cyclophosphamide on hippocampal structure of adult male rats (role of rosuvastatin). Military Medical Science Letters, 91(3), 256-264. [DOI:10.31482/mmsl.2022.022]
Al-Allaf, L. I., Mammdoh, J. K., & Ahmed, A. A. (2022). The histologic effects of high doses of botulinum toxin a on the rabbit's salivary gland. Iraqi Journal of Veterinary Sciences, 36(4), 1111-1117. [DOI:10.33899/ijvs.2022.133149.2184]
Ali, B. F., Abu-Raghif, A. R., Ridha-Salman, H., & Al-Athari, A. J. H. (2025). Vildagliptin topical ointment: An effective treatment for imiquimod-induced psoriasis in mice. Journal of Molecular Histology, 56(3), 143. [DOI:10.1007/s10735-025-10416-4] [PMID]
Al–Moula, A. D., Al-Mashhadane, F. A., & Jawna’a, K. M. (2012). Effects of 6–mercaptopurine on salivary glands in rabbit. Al-Rafidain Dental Journal, 12(2), 266–273. [Link]
Al-Saffar, M. T., & Taqa, A. A. (2019). The effects of luteolin nanoparticles on the healing of extracted tooth socket in rabbits.Journal of Oral Research, 18(1), 15-18. [Link]
Al-Saffar, M. T., Mahmood, A. S., & Sulaiman, M. S. (2020). Impact of local anesthesia on wound healing. Indian Journal of Forensic Medicine & Toxicology, 14(4), 1869-1874. [Link]
Attarbashee, R. (2025). The antitoxic effect of the rosuvastatin in the cyclophosphamide-induced liver toxicity in male rats. Assiut Veterinary Medical Journal, 71(185), 187-203. [DOI:10.21608/avmj.2025.330356.1445]
Attarbashee, R. K., Hamodat, H. F., Mammdoh, J. K., & Ridha-Salman, H. (2025). The Possible effect of Bosentan on the methotrexate-induced salivary gland changes in male rats: histological and Immunohistochemical study. Toxicology Research, 14(1), tfaf007. [DOI:10.1093/toxres/tfaf007] [PMID]
Attarbashee, R. K., Mammdoh, J. K., & Al-Kazzaz, S. G. (2023). The protective effect of bosentan on methotrexate-induced oral mucositis in rats. Iraqi Journal of Veterinary Sciences, 37 (3), 629-635. [DOI:10.33899/ijvs.2023.135827.2536]
Bao, X., Li, W., Jia, R., Meng, D., Zhang, H., & Xia, L. (2023). Molecular mechanism of ferulic acid and its derivatives in tumor progression. Pharmacological Reports: PR, 75(4), 891–906.[DOI:10.1007/s43440-023-00494-0][PMID]
Bayramoglu, Z., Mokhtare, B., Mendil, A. S., Coban, T. A., Mammadov, R., & Bulut, S., et al. (2022). Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: Biochemical and histopathological evaluation. Journal of Applied Oral Science: Revista FOB, 30, e20220115.[DOI:10.1590/1678-7757-2022-0115][PMID]
Chibly, A. M., Aure, M. H., Patel, V. N., & Hoffman, M. P. (2022). Salivary gland function, development, and regeneration. Physiological Reviews, 102(3), 1495–1552. [DOI:10.1152/physrev.00015.2021][PMID]
Dawood, J. O., & Abu-Raghif, A. (2023). Moxifloxacin's Therapeutic Effects in AA-Induced Colitis: Anti-Inflammatory Action through NF-κB pathway inhibition, including TNF-α Pathway and downstream inflammatory processes. Journal of Contemporary Medical Sciences, 9(4).239-244. [Link]
DiNicolantonio, J. J., McCarty, M. F., Assanga, S. I., Lujan, L. L., & O'Keefe, J. H. (2022). Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity. Open Heart, 9(1), e001801. [DOI:10.1136/openhrt-2021-001801][PMID]
Ferro, C., Florindo, H. F., & Santos, H. A. (2021). Selenium nanoparticles for biomedical applications: From development and characterization to therapeutics. Advanced Healthcare Materials, 10(16), e2100598. [DOI:10.1002/adhm.202100598] [PMID]
Hamzah, N. A., Al-Mashhadane, F.A., & Hamdon, S. M. (2023). Antioxidant and anti-inflammatory effects of garlic (Allium sativum) extracts in healing of induced oral ulcer in rabbits. AIP Conference Proceedings, 2839, 080005. [DOI:10.1063/5.0167803]
Heller, D., Nery, G. B., Bachi, A. L. L., & Al-Hashimi, I. (2025). Positive role of saliva in the oral microbiome. Advances in Experimental Medicine and Biology, 1472, 103–118.[DOI:10.1007/978-3-031-79146-8_7] [PMID]
Joshi, P., Joshi, S., Semwal, D., Bisht, A., Paliwal, S., & Dwivedi, J., et al. (2021). Curcumin: An insight into molecular pathways involved in anticancer activity. Mini Reviews in Medicinal Chemistry, 21(17), 2420–2457. [DOI:10.2174/1389557521666210122153823] [PMID]
Khatun, M. M., Bhuia, M. S., Chowdhury, R., Sheikh, S., Ajmee, A., & Mollah, F., et al. (2024). Potential utilization of ferulic acid and its derivatives in the management of metabolic diseases and disorders: An insight into mechanisms. Cellular Signalling, 121, 111291. [DOI:10.1016/j.cellsig.2024.111291] [PMID]
Kızıl, H. E., Caglayan, C., Darendelioğlu, E., Ayna, A., Gür, C., & Kandemir, F. M., et al. (2023). Morin ameliorates methotrexate-induced hepatotoxicity via targeting Nrf2/HO-1 and Bax/Bcl2/Caspase-3 signaling pathways. Molecular Biology Reports, 50(4), 3479–3488. [DOI:10.1007/s11033-023-08286-8] [PMID]
Kumar, M., Kaushik, D., Shubham, S., Kumar, A., Kumar, V., Oz, E., & Brennan, C., et al. (2025). Ferulic acid: Extraction, estimation, bioactivity and applications for human health and food. Journal of The Science of Food and Agriculture, 105(8), 4168–4177. [DOI:10.1002/jsfa.13931][PMID]
Liu, Y., Shi, L., Qiu, W., & Shi, Y. (2022). Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation. Molecular & Cellular Toxicology, 18(4), 509–519. [DOI:10.1007/s13273-021-00219-5][PMID]
Luty, R. S. (2021). The effect of Moringa oleifera on high fat diet and Streptozotocin induced diabetic rats. Iranian Journal of Pharmaceutical Sciences, 17(2), 11-24. [Link]
Mammdoh, J. K., Attarbashii, R. K. A., & Almola, A. D. (2023). Protective effect of rosuvastatin on cyclophosphamide-induced oral toxicity in rats: Histological and immunohistochemical study. Research Journal of Pharmacy and Technology, 16(2), 759-762. [DOI:10.52711/0974-360X.2023.00129]
Marin, G. E., Neag, M. A., Burlacu, C. C., & Buzoianu, A. D. (2022). The protective effects of nutraceutical components in methotrexate-induced toxicity models-an overview. Microorganisms, 10(10), 2053. [DOI:10.3390/microorganisms10102053][PMID]
Mohammed, D. S., & Al-Gareeb, A. I. A. (2021). Effects of omega-3 and vitamin c on methotrexate-induced liver injury. Mustansiriya Medical Journal, 20(2), 39-44. [DOI:10.4103/MJ.MJ_6_21]
Mostafa, O. A. A., Ibrahim, F., & Borai, E. (2023). Protective effects of hesperidin in cyclophosphamide-induced parotid toxicity in rats. Scientific Reports, 13(1), 158. [DOI:10.1038/s41598-022-26881-w][PMID]
Moubarak, H. (2024). Histological and immunohistochemical analysis of possible ameliorative effect of ashwagandha on methotrexate-induced oral mucositis in albino rats. Egyptian Dental Journal, 70(2), 1261-1274. [DOI:10.21608/edj.2024.261718.2875]
Mustafa, I. O., Jimoh, L., & Tanko, Y. (2025). Pinocembrin isolated from Nigerian propolis prevents elevation of cytokines implicated in the aetiology of diabetic retinopathy in rat models of diabetes mellitus. Archives of Razi Institute, 80(3), 783-790. [Link]
Naji, M. E., Gatea, F. K., Ali, K. A., & Raghif, A. R. A. (2022). Effect of convolvulus arvensis ethanolic extract on testosterone-induced alopecia in mice. International Journal of Drug Delivery Technology, 12(3), 1070-1075. [DOI:10.25258/ijddt.12.3.24]
Park, J. E., & Han, J. S. (2024). Improving the effect of ferulic acid on inflammation and insulin resistance by regulating the JNK/ERK and NF-κB pathways in TNF-α-treated 3T3-L1 adipocytes. Nutrients, 16(2), 294. [DOI:10.3390/nu16020294][PMID]
Ridha-Salman, H., Al-Zubaidy, A. A., Abbas, A. H., Hassan, D. M., & Malik, S. A. (2025). The alleviative effects of canagliflozin on imiquimod-induced mouse model of psoriasis-like inflammation. Naunyn-Schmiedeberg's Archives of Pharmacology, 398(3), 2695–2715. [DOI:10.1007/s00210-024-03406-y] [PMID]
Salman, H. R., Al-Khafaji, B. A., & Mohammed, N. J. (2013). Effect of Apium graveolens leaves and stalks in reducing the side effects of doxorubicin in male rabbits. Medical Journal of Babylon, 10(1), 46-74. [Link]
Saud, M. A., Saud, N. A., Hamad, M. A., & Farhan Gar, L. (2022). Role of Salvia officinalis silver nanoparticles in attenuation renal damage in rabbits exposed to methotrexate. Archives of Razi Institute, 77(1), 151-162. [DOI:10.22092/ari.2021.356313.1821] [PMID]
Shi, Y., Shi, L., Liu, Q., Wang, W., & Liu, Y. (2023). Molecular mechanism and research progress on pharmacology of ferulic acid in liver diseases. Frontiers in Pharmacology, 14, 1207999.[DOI:10.3389/fphar.2023.1207999][PMID]
Sultan, O. N., & Taqa, G. A. (2024). Physiological and histological effects of apigenin and luteolin on cytarabine injected rats. Baghdad Science Journal, 21(1), 1. [DOI:10.21123/bsj.2023.7000]
Taghyan, S. A., Mahmoud, E. F., Taha, R., & Shamel, M. (2025). Protective effects of nigella sativa against acrylamide-induced toxicity in submandibular salivary glands of albino rats: A Histological and molecular study. Archives of Razi Institute Journal, 80(5), 1209-1216. [Link]
Zhai, Y., Wang, T., Fu, Y., Yu, T., Ding, Y., & Nie, H. (2023). Ferulic Acid: A Review of pharmacology, toxicology, and therapeutic effects on pulmonary diseases. International Journal of Molecular Sciences, 24(9), 8011. [DOI:10.3390/ijms24098011][PMID]
| ||
|
آمار تعداد مشاهده مقاله: 20 تعداد دریافت فایل اصل مقاله: 20 |
||