Silymarin mitigates diclofenac-induced liver toxicity through inhibition of inflammation and oxidative stress in male rats

Pantea Ramezannezhad ¹ , Ali Nouri ² * , Esfandiar Heidarian ²

Cited by CrossRef: 17

1- Liu Y, Li H, Zhao Z, Pan S, Ren Y, Kong L, Chen Z, Zhou Y, Qu Y, Du J, Mai K, Ai Q. Role of dietary silymarin in growth, hepatic lipid homeostasis, antioxidant status, and inflammation in juvenile large yellow croaker (Larimichthys crocea) fed soybean oil-based diets. Aquaculture. 2026;:744571 [Crossref]

2- Basheeruddin M, Lavanya V, Ahmed N, Jamal S. Organic osmolyte betaine mitigates the deleterious effects of Diclofenac in vivo in wistar albino rats. Braz J Pharm Sci. 2023;59 [Crossref]

3- Oyinloye O, Murtala A, Oladoja F, Okunye O, Kasumu E, Iloka P. Ethyl acetate fraction of Mucuna pruriens leaves mitigates diclofenac-induced hepatotoxicity via modulation of biochemical and histological parameters changes in Wistar Rats. PHAR. 2023;70(4):1201 [Crossref]

4- Esmaeilzadeh M, Heidarian E, Shaghaghi M, Roshanmehr H, Najafi M, Moradi A, Nouri A. Gallic acid mitigates diclofenac-induced liver toxicity by modulating oxidative stress and suppressingIL-1βgene expression in male rats. Pharmaceutical Biology. 2020;58(1):590 [Crossref]

5- Amini S, Bagherniya M, Butler A, Askari G, Sahebkar A. The effect of medicinal plants on cirrhosis: A systematic review of clinical trials. Phytotherapy Research. 2023;37(7):3083 [Crossref]

6- Santhakumar P, Roy A, Ganesh M, Selvaraj J, Prathap L, Babu K. Ethanolic extract of Capparis decidua fruit ameliorates methotrexate-induced hepatotoxicity by suppressing oxidative stress and inflammation by modulating nuclear factor-kappa B signaling pathway. Phcog Mag. 2021;17(6):143 [Crossref]

7- Moradi A, Abolfathi M, Javadian M, Heidarian E, Roshanmehr H, Khaledi M, Nouri A. Gallic Acid Exerts Nephroprotective, Anti-Oxidative Stress, and Anti-Inflammatory Effects Against Diclofenac-Induced Renal Injury in Malerats. Archives of Medical Research. 2021;52(4):380 [Crossref]

8- Safi A, Mohammadi S, Emami M, Radaei A, Kalantari-Hesari A, Nouri A, Rahimi-Madiseh M, Ahmadi R. Thymoquinone mitigates diclofenac-induced hepatorenal toxicity in male Wistar rats by balancing the redox state and modulating Bax/Bcl-2/caspase-3 apoptotic pathways and NF-κB signaling. 2025;20(1):95 [Crossref]

9- Ekinci B, Altuner D, Suleyman B, Mammadov R, Bulut S, Suleyman Z, A. Gul M, Ergul C, Suleyman H. Effect of Thymoquinone on Diclofenac-Induced Liver Injury. International J of Pharmacology. 2022;18(6):1331 [Crossref]

10- El Sayed N, Noureldin M, El Sayed I, El Banna Y, Ghoneim M. Alogliptin repositioning confers protection against diclofenac-induced liver injury by inhibiting TLR4/NF-κB, ROS/TXNIP, and NLRP3 inflammasome-mediated pyroptosis in rats. Naunyn-Schmiedeberg's Arch Pharmacol. 2026;399(5):6983 [Crossref]

11- Hassanpour Z, Shirazi F, Shokrpoor S, Yarahmadi R, Moghadasi N, Vosoogh M, Ashtarinezhad A. The effect of subacute co-exposure to carbon tetrachloride and diclofenac on the liver of male wistar rats. Toxicol Ind Health. 2023;39(7):364 [Crossref]

12- Talukder S, Islam S, Islam S, Akanda M, Siddiqui M. Protective role of Silymarin in the mitigation of methotrexate induced biometrical and haemato-biochemical alterations of liver in rabbits. Discov Appl Sci. 2026;8(4) [Crossref]

13- Salama A, Ashoura N, Esmail K, Tohamy H, Shukry M, Alotaibi B, Aboushouk A. Melissa officinalis Attenuates Diclofenac‐Induced Hepatorenal Toxicity via AMPK/SIRT1 and STAT3/Nrf2 Pathways. J of Applied Toxicology. 2025;45(8):1649 [Crossref]

14- Karimi-Dehkordi M, Saghaei F, Hoseini E. Inhibition of Inflammatory Signals “HMGB1, NLRP3, TNF-α, IL-1β” and Oxidative Stress in Diclofenac-Induced Hepatotoxicity in Rats Using Hydroalcoholic Extract of Dracocephalum kotschyi. Iran J Pharm Res. 2025;24(1) [Crossref]

15- Dockalova H, Zeman L, Horky P. Influence of Milk Thistle (Silybum marianum) Seed Cakes on Biochemical Values of Equine Plasma Subjected to Physical Exertion. Animals. 2021;11(1):210 [Crossref]

16- Tabari M, Houshyar M, Araghi A, Mirzakhani N, Crescenzo G, Cardone R, Zizzadoro C. Nephroprotective and hepatoprotective effects of lemongrass essential oil and citral on diclofenac-induced toxicity in mice. Biomedicine & Pharmacotherapy. 2024;180:117541 [Crossref]

17- Barzan M, Heydari M, Mirshekari-Jahangiri H, Firouzi H, Dastan M, Najafi M, Khaledi M, Nouri A, Shah-abadi M. Carvacrol Exerts Anti-Inflammatory, Anti-Oxidative Stress and Hepatoprotective Effects against Diclofenac-Induced Liver Injury in Male Rats. 2023;14(1) [Crossref]

18- Talukder S, Islam S, Islam S, Akanda R, Siddiqui S. Protective Role of Silymarin Against Methotrexate Induced Nephropathy in Rabbits. J Biochem & Molecular Tox. 2025;39(10) [Crossref]

19- Hatefi-Hesari F, Heydari M, Hosseinzadeh M, Moridi A, Bahrami R, Khaledi M, Nouri A. Protective Effect of Ellagic Acid on Induced Liver Injury. Rev Bras Farmacogn. 2021;31(6):814 [Crossref]

20- Elkot M, Nematalla H, Abdel-Raheem I, Ghoneim A. Protective effects of glycine against diclofenac-induced toxicity in isolated rat hepatocytes. Drug and Chemical Toxicology. 2026;49(5):1021 [Crossref]

21- Bouyahya A, Guaouguaou F, El Omari N, El Menyiy N, Balahbib A, El-Shazly M, Bakri Y. Anti-inflammatory and analgesic properties of Moroccan medicinal plants: Phytochemistry, in vitro and in vivo investigations, mechanism insights, clinical evidences and perspectives. Journal of Pharmaceutical Analysis. 2022;12(1):35 [Crossref]

22- Karimi-Matloub S, Namavari R, Hatefi-Hesari F, Sadeghi A, Karimi-Matloub R, Khaledi M, Bakhtiari A, Nouri A. The nephroprotective effect of ellagic acid against diclofenac-induced renal injury in male rats: role of Nrf2/HO-1 and NF-κB/TNF-α pathways. Biologia. 2022;77(12):3633 [Crossref]

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