The Effect of Baicalin on Cisplatin-Induced Oxidative Damage in the Parotid Gland

Abstract

Objective: Cisplatin is one of the widely used chemotherapeutic agents; however, its therapeutic potential is significantly limited due to oxidative tissue injury. The aim of this study is to investigate the effects of baicalin on cisplatin-induced parotid gland damage . Materials and Methods: Twenty-eight adult female rats were randomly assigned to four groups: Control, Baicalin (BA), Cisplatin (CPDD), and CPDD + BA. Dimethyl sulfoxide (DMSO), used as a vehicle, was administered daily intraperitoneally (i.p.) to the Control and CPDD groups. Cisplatin (7 mg/kg, i.p.) was given as a single dose to the CPDD and CPDD + BA groups on the first day. Baicalin (100 mg/kg, daily, i.p.) was administered to the BA and CPDD + BA groups. On day six, all rats were sacrificed, and parotid glands were collected for histological and biochemical analyses. Results: In the CPDD group, degenerated acinar and ductal cells with cytoplasmic vacuolization, pyknotic nuclei, dilated ducts with stagnant secretion in the lumen, and vascular congestion were observed. Additionally, significantly higher total oxidant status (TOS) and oxidative stress index (OSI) and lower total antioxidant status (TAS) were detected in this group. In the CPDD+BA group, baicalin treatment significantly reversed TAS, TOS, and OSI levels in compared to the CPDD group. Also, a prominent improvement in morphological damage was observed in the parotid gland of this group compared to the CPDD group. Conclusion: Our findings suggest that baicalin may have a protective effect against cisplatin-induced toxicity due to its antioxidant properties

Keywords

• baicalin
• Cisplatin
• Parotid gland
• Oxidative damage

Baikalinin Parotis Bezinde Sisplatin ile İndüklenen Oksidatif Hasar Üzerine Etkisi

Abstract

Amaç: Sisplatin, yaygın olarak kullanılan bir kemoterapötik ajan olmakla birlikte, oksidatif doku hasarı gibi yan etkileri nedeniyle terapötik potansiyeli önemli ölçüde sınırlanmaktadır. Bu çalışmanın amacı, baikalinin sisplatin kaynaklı parotis bezi hasarına karşı etkilerini araştırmaktır. Materyal ve Yöntemler: Yirmi sekiz yetişkin dişi sıçan rastgele dört gruba ayrıldı: Kontrol, Baikalin (BA), Sisplatin (CPDD) ve CPDD + BA. Kontrol ve CPDD gruplarına, taşıyıcı solüsyon olan dimetil sülfoksit (DMSO) günlük olarak intraperitoneal (i.p.) yolla verildi. Sisplatin (7 mg/kg, i.p.) deneyin ilk gününde tek doz olarak CPDD ve CPDD + BA gruplarına uygulandı. Baikalin (100 mg/kg, günlük, i.p.) ise BA ve CPDD + BA gruplarına verildi. Altıncı günde tüm sıçanlar sakrifiye edilerek parotis bezleri histolojik ve biyokimyasal analizler için toplandı. Bulgular: CPDD grubunda, sitoplazmik vakuolizasyon ve piknotik çekirdekler içeren hasarlı asiner ve kanal hücreleri, lümeninde salgı içeren genişlemiş kanallar ve vasküler konjesyon gözlendi. Ayrıca, bu grupta total oksidan seviyesi (TOS) ve oksidatif stres indeksi (OSİ) seviyeleri anlamlı derecede yüksek, total antioksidan seviyesi (TAS) anlamlı derecede azalmış olarak tespit edildi. CPDD+BA grubunda ise, baikalin tedavisi TAS, TOS ve OSİ seviyelerini CPDD grubuna kıyasla anlamlı şekilde tersine çevirdi. Ayrıca, CPDD grubuna kıyasla bu grubun parotis bezinde morfolojik hasarda belirgin bir iyileşme gözlenmiştir. Sonuç: Bulgularımız, baikalinin antioksidan özellikleri nedeniyle sisplatin kaynaklı toksisiteye karşı koruyucu bir etkiye sahip olabileceğini düşündürmektedir.

Keywords

• Baikalin
• Sisplatin
• Parotis bez
• Oksidatif hasar

References

1. Al-Refai AS, Khaleel AK, Ali S. The effect of green tea extract on submandibular salivary gland of methotrexate treated albino rats: immunohistochemical study. J. Cytol. Histol. 2014;5(2):1.
2. Badawy AM, İbrahim M, Taha M, Helal Aİ, Elmetwally AAM, El-Shenbaby I et al. Melatonin mitigates cisplatin-induced submandibular gland damage by inhibiting oxidative stress, inflammation, apoptosis, and fibrosis. Cureus. 2024;16(9):e68515.
3. Bajek-Bil A, Chmiel M, Włoch A, Stompor-Gorący M. Baicalin-current trends in detection methods and health-promoting properties. Pharmaceuticals (Basel). 2023;16(4):570.
4. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur. J. Pharmacol. 2014;740:364-478.
5. Dessoukey SM, Halawa AM, Fathy IA, Kashkoush DM. The effect of adipose derived stem cells versus platelet rich plasma in ameliorating cisplatin-induced injury on the submandibular salivary gland.” A comparative histological study”. Egypt. J. Histol. 2021;44(2):406-417.
6. Diniz CKS, Oliveira MDLD, Viana Filho JMC. Assessment of hyposalivation and xerostomia in cancer patients undergoing chemotherapy treatment. Rev. Bras. Cancerol. 2025;70(2):e-184639.
7. El-Ela SRA, Zaghloul RA, Eissa LA. Promising cardioprotective effect of baicalin in doxorubicin-induced cardiotoxicity through targeting toll-like receptor 4/nuclear factor-κB and Wnt/β-catenin pathways. Nutrition. 2022;102:111732.
8. El-Haddad KES. Effect of cisplatin on albino rats parotid gland and the possible protective action of sesame and moringa oils. Egypt. Dent. J. 2024;70(2):1387-1398.

9. El-Messiry H, El Shaer DF, Fathy IA. A comparative histological and immunohistochemical study on the effect of moringa oil and sesame oil on the submandibular glands of cisplatin treated albino rats. Egypt. Dent. J. 2023;69(2):1161-1180.
10. Elgamily MF, Denewar M. Potential benefit of Annona muricata extract in combating cisplatin-induced injury of parotid gland in albino rats. Egypt. Dent. J. 2020;66(2):997–1007.
11. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin. Biochem. 2005;38(12):1103-1111.
12. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin. Biochem. 2004;37(4):277-285.
13. Farouk H, Nasr M, Elbaset MA, Shabana ME, Ahmed-Farid OAH, Ahmed RF. Baicalin nanoemulsion mitigates cisplatin-induced hepatotoxicity by alleviating oxidative stress, inflammation, and restoring cellular integrity. Toxicol. Appl. Pharmacol. 2025;495:117231.
14. Florea AM, Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel). 2011;3(1):1351-1371.
15. Fouad AA, Qutub HO, Jresat I. Dose-dependent protective effect of baicalin against testicular torsion-detorsion in rats. Andrologia. 2017;49(1): e12580.
16. Gao W, Xu B, Zhang Y, Liu S, Duan Z, Chen Y et al. Baicalin attenuates oxidative stress in a tissue-engineered liver model of NAFLD by scavenging reactive oxygen species. Nutrients. 2022;14(3):541.
17. Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg. Chem. 2019;88:102925.
18. Hany E, Sobh MA, ElKhier MTA, ElSabaa HM, Zaher AR. The Effect of different routes of injection of bone marrow mesenchymal stem cells on parotid glands of rats receiving cisplatin: A comparative study. Int. J. Stem Cells. 2017;10(2):169-178.
19. Kadarullah O, Tamtomo DG, Wasita B, Setiamika M, Prayitno A, Widyaningsih V et al. Cisplatin-induced oral mucositis prevention: Nigella sativa’s anti-inflammatory role through NFκB pathway. Trends Sci. 2024;21(9):8105-8105.
20. Katanić Stanković JS, Selaković D, Rosić G. Oxidative damage as a fundament of systemic toxicities induced by cisplatin-the crucial limitation or potential therapeutic target? Int. J. Mol. Sci. 2023;24(19):14574.
21. Kitashima S. Morphological alterations of submandibular glands caused by cisplatin in the rat. Kurume Med. J. 2005;52(1-2):29-38.
22. Krasuska-Sławińska E, Brożyna A, Dembowska-Bagińska B, Olczak-Kowalczyk D. Antineoplastic chemotherapy and congenital tooth abnormalities in children and adolescents. Contemp. Oncol (Pozn). 2016;20(5):394-401.
23. Mentese A, Alemdar NT, Livaoglu A, Ayazoglu Demir E, Aliyazicioglu Y, Demir S. Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study. J. Obstet. Gynaecol. 2022;42(8):3584-3590.
24. Moawad AAR, Elhindawy M. The possible protective effect of graviola extract on salivary gland against cytotoxicity during cisplatin treatment (histological, biochemical and immuno-histochemical study). Egypt. Dent. J. 2022;45(2):588-596.
25. Qian Y, Chen Y, Wang L, Tou J. Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB protein expressions in rats with severe acute pancreatitis. Acta Cir. Bras. 2018;33(7):556-564.
26. Ren W, Cha X, Xu R, Wang T, Liang C, Chou J, et al. Cisplatin attenuates taste cell homeostasis and induces inflammatory activation in the circumvallate papilla. Theranostics. 2023;13(9):2896-2913.
27. Romani AMP. Cisplatin in cancer treatment. Biochem. Pharmacol. 2022;206:115323.
28. Shehata AYA, Younis SA, Rashad NA, Mohamed AA. Cisplatin induced injury on rat submandibular salivary gland (histological and ultrastructural evaluation). Alex. Dent. J. 2024;49(3):94-99.
29. 29. Zhang HJ, Luo JZ, Lan CI, Teng X, Ge B, Liu JQ et al. Baicalin protects against hepatocyte injury caused by aflatoxin B1 via the TP53-related ferroptosis pathway. Ecotoxicol. Environ. Saf. 2024;281:116661.