Potential Cardioprotective Effects of Garlic Components Against Experimental Cardiac Damage in Rats

Authors

DOI:

https://doi.org/10.58600/eurjther2799

Keywords:

Allyl disulfide, cisplatin, cardiotoxicity, histopathology, S-Allyl-L-Cysteine

Abstract

Objective: Cisplatin (CIS) is a frequently used chemotherapeutic drug; nevertheless, its clinical efficacy is limited by cardiotoxicity, mostly due to oxidative stress and apoptosis. Natural antioxidants such as S-Allyl-L-Cysteine (SAC) and Allyl Disulfide (ADS)—organosulfur compounds derived from garlic—exhibit potential in mitigating such damage. This study aimed to evaluate CIS-induced cardiotoxicity in rats and investigate the potential for SAC and ADS to reduce this toxicity.

Methods: Four groups -Control, CIS, CIS + SAC, and CIS + ADS- were randomly assigned to thirty-two female Sprague Dawley rats. On days 1 and 8 of the experiment, CIS was given intraperitoneally at a dose of 5 mg/kg, and for 14 days in a row, SAC and ADS were given orally by gavage at a dose of 100 mg/kg. Using Hematoxylin-Eosin (H&E) and Periodic Acid-Schiff (PAS) staining, heart tissues were excised at the termination of the experiment and examined histopathologically.

Results: In the CIS group, prominent histopathological changes, including interstitial congestion, lymphocytic infiltration, edema, and vacuolar degeneration in cardiomyocytes, were observed. PAS staining showed glycoprotein accumulation and chondromatous metaplasia. All these changes were reversed in either the CIS+SAC group or the CIS+ADS group by improving cardiac architecture and lowering levels of congestion, edema, and degeneration.

Conclusion: This study shows that SAC and ADS have protective effects against CIS-induced cardiotoxicity. These natural antioxidants may be used to prevent cardiotoxicity that is induced by chemotherapy.

References

González A, García-Gómez-Heras S, Franco-Rodríguez R, López-Miranda V, Herradón E (2023) Cisplatin cycles treatment sustains cardiovascular and renal damage involving TLR4 and NLRP3 pathways. Pharmacol Res Perspect. 11(4):e01108. https://doi.org/10.1002/prp2.1108

Bayrak S, Aktaş S, Altun Z, Çakir Y, Tütüncü M, Kum Özşengezer S, Yilmaz O, Olgun N (2020) Antioxidant effect of acetyl-L-carnitine against cisplatin-induced cardiotoxicity. J Int Med Res. 48(1):300060520951393. https://doi.org/10.1177/0300060520951393

Dasari S, Njiki S, Mbemi A, Yedjou CG, Tchounwou PB (2022) Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy. Int J Mol Sci. 23(3):1532. https://doi.org/10.3390/ijms23031532

Samavati I, Ranjbar A, Haddadi R (2024) Cardioprotective effect of vitamin D3 on cisplatin-induced cardiotoxicity in male mice: role of oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 397(7):4761–4769. https://doi.org/10.1007/s00210-023-02848-0

Hesari M, Mohammadi P, Moradi M, Shackebaei D, Yarmohammadi F (2024) Molecular mechanisms involved in therapeutic effects of natural compounds against cisplatin-induced cardiotoxicity: a review. Naunyn Schmiedebergs Arch Pharmacol. 397(11):8367–8381. https://doi.org/10.1007/s00210-024-03207-3

Yudhistira B, Punthi F, Lin JA, Sulaimana AS, Chang CK, Hsieh CW (2022) S-Allyl cysteine in garlic (Allium sativum): Formation, biofunction, and resistance to food processing for value-added product development. Compr Rev Food Sci Food Saf. 21(3):2665-2687. https://doi.org/10.1111/1541-4337.12937

Amano H, Kazamori D, Itoh K (2016) Pharmacokinetics of S-allyl-L-cysteine in rats is characterized by high oral absorption and extensive renal reabsorption. J Nutr. 146(2):456S–459S. https://doi.org/10.3945/jn.114.201749

Rauf A, Abu-Izneid T, Thiruvengadam M, Imran M, Olatunde A, Shariati MA, Bawazeer S, Naz S, Shirooie S, Sanches-Silva A, Farooq U, Kazhybayeva G (2022) Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties. Curr Top Med Chem. 22(11):957-972. https://doi.org/10.2174/1568026621666211105094939

Huang YT, Yao CH, Way CL, Lee KW, Tsai CY, Ou HC, Kuo WW (2013) Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing survival pathways in experimental diabetic rats. J Appl Physiol. 114(3):402–410. https://doi.org/10.1152/japplphysiol.00672.2012

Valaei K, Taherkhani S, Arazi H, Suzuki K (2021) Cardiac oxidative stress and the therapeutic approaches to the intake of antioxidant supplements and physical activity. Nutrients. 13(10):3483. https://doi.org/10.3390/nu13103483

Colín-González AL, Santana RA, Silva-Islas CA, Chánez-Cárdenas ME, Santamaría A, Maldonado PD (2012) The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine-induced protection. Oxid Med Cell Longev. 907162. https://doi.org/10.1155/2012/907162

Abudalo R, Gammoh O, Altaber S, Bseiso Y, Qnais E, Wedyan M, Oqal M, Alqudah A (2024) Mitigation of cisplatin-induced cardiotoxicity by Isorhamnetin: Mechanistic insights into oxidative stress, inflammation, and apoptosis modulation. Toxicol Rep. 12:564–573. https://doi.org/10.1016/j.toxrep.2024.05.003

Bahadır A, Ceyhan A, Öz Gergin Ö, Yalçın B, Ülger M, Özyazgan TM, Yay A (2018) Protective effects of curcumin and beta-carotene on cisplatin-induced cardiotoxicity: An experimental rat model. Anatol J Cardiol. 19(3):213–221. https://doi.org/10.14744/AnatolJCardiol.2018.53059

Gunturk EE, Yucel B, Gunturk I, Yazici C, Yay A, Kose K (2019) The effects of N-acetylcysteine on cisplatin induced cardiotoxicity. Bratisl Lek Listy. 120(6):423-428. https://doi.org/10.4149/BLL_2019_068

Xu J, Zhang B, Chu Z, Jiang F, Han J (2021) Wogonin alleviates cisplatin-induced cardiotoxicity in mice via inhibiting gasdermin D-mediated pyroptosis. J Cardiovasc Pharmacol. 78(5):597–603. https://doi.org/10.1097/FJC.0000000000001085

El-Sawalhi MM, Ahmed LA (2014) Exploring the protective role of apocynin, a specific NADPH oxidase inhibitor, in cisplatin-induced cardiotoxicity in rats. Chem Biol Interact. 207:58–66. https://doi.org/10.1016/j.cbi.2013.11.008

Al-Majed AA, Sayed-Ahmed MM, Al-Yahya AA, Aleisa AM, Al-Rejaie SS, Al-Shabanah OA (2006) Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. Pharmacol Res. 53(3):278–286. https://doi.org/10.1016/j.phrs.2005.12.005

Oliveira CA, Mercês ÉAB, Portela FS, Malheiro LFL, Silva HBL, De Benedictis LM, De Benedictis JM, Silva CCDE, Santos ACL, Rosa DP, Velozo HS, de Jesus Soares T, de Brito Amaral LS (2024) An integrated view of cisplatin-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity: characteristics, common molecular mechanisms, and current clinical management. Clin Exp Nephrol. 28(8):711-727. https://doi.org/10.1007/s10157-024-02490-x

El-Awady el-SE, Moustafa YM, Abo-Elmatty DM, Radwan A (2011) Cisplatin-induced cardiotoxicity: Mechanisms and cardioprotective strategies. Eur J Pharmacol. 650(1):335–341. https://doi.org/10.1016/j.ejphar.2010.09.085

El-Hawwary AA, Omar NM (2019) The influence of ginger administration on cisplatin-induced cardiotoxicity in rat: Light and electron microscopic study. Acta Histochem. 121(5):553–562. https://doi.org/10.1016/j.acthis.2019.04.013

Sangeetha T, Quine SD (2009) Preventive effect of S-allyl cysteine sulphoxide (alliin) on mitochondrial dysfunction in normal and isoproterenol-induced cardiotoxicity in male Wistar rats: A histopathological study. Mol Cell Biochem. 328(1-2):1–8. https://doi.org/10.1007/s11010-009-0066-9

Padmanabhan M, Prince PS (2006) Preventive effect of S-allylcysteine on lipid peroxides and antioxidants in normal and isoproterenol-induced cardiotoxicity in rats: a histopathological study. Toxicology. 224(1-2):128-137. https://doi.org/10.1016/j.tox.2006.04.039

Khatua TN, Dinda AK, Putcha UK, Banerjee SK (2015) Diallyl disulfide ameliorates isoproterenol-induced cardiac hypertrophy activating mitochondrial biogenesis via eNOS-Nrf2-Tfam pathway in rats. Biochem Biophys Rep. 5:77–88. https://doi.org/10.1016/j.bbrep.2015.11.008

Zeng T, Zhang CL, Song FY, Zhao XL, Yu LH, Zhu ZP, Xie KQ (2013) The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress. Biochim Biophys Acta. 1830(10):4848–4859. https://doi.org/10.1016/j.bbagen.2013.06.028

Pichler Sekulic S, Sekulic M (2023) Chondromatous metaplasia within native cardiac valves: clinicopathologic characterization with particular focus upon aortic valves. APMIS. 131(8):410-418. https://doi.org/10.1111/apm.13340

Torre M, Hwang DH, Padera RF, Mitchell RN, VanderLaan PA (2016) Osseous and chondromatous metaplasia in calcific aortic valve stenosis. Cardiovasc Pathol. 25(1):18-24. https://doi.org/10.1016/j.carpath.2015.08.008

Wu CH, Chou WC, Jou IM, Tu YK, Ma CH, Tsai KL (2025) Cisplatin-induced oxidative stress, apoptosis, and pro-inflammatory responses in chondrocytes through modulating LOX-1. J Orthop Surg Res. 20(1):206. https://doi.org/10.1186/s13018-025-05602-9

Bradley JM, Organ CL, Lefer DJ (2016) Garlic-derived organic polysulfides and myocardial protection. J Nutr. 146(2):403S–409S. https://doi.org/10.3945/jn.114.208066

Banerjee SK, Maulik SK (2002) Effect of garlic on cardiovascular disorders: a review. Nutr J. 1:4. https://doi.org/10.1186/1475-2891-1-4

Figure 3. The histopathological scores of the experimental groups. Different lowercase letters indicate statistically significant differences between groups (p < 0.001), as determined by one-way ANOVA followed by Tukey’s post hoc test.

Downloads

Published

2025-11-27

How to Cite

Canbaz, H. T., Arslan, H., & Çetinkaya Karabekir, S. (2025). Potential Cardioprotective Effects of Garlic Components Against Experimental Cardiac Damage in Rats. European Journal of Therapeutics, 32(1), 12–19. https://doi.org/10.58600/eurjther2799

Issue

Section

Original Articles

Categories