Ellagic Acid Mitigates Hepato-renal Toxicity Induced by Tacrolimus in Wistar Rats

AuthorMohammad Amin Behmaneshen
AuthorSima Janatien
AuthorMohammad Khanifaren
AuthorFardis Masoudipouren
AuthorFatemeh Pourmotaharien
AuthorSeyedeh Mahsa Poormoosavien
OrcidMohammad Amin Behmanesh [0000-0002-4292-5381]en
OrcidSima Janati [0000-0001-5582-7177]en
OrcidSeyedeh Mahsa Poormoosavi [0000-0001-6641-6808]en
Issued Date2026-03-31en
AbstractBackground: Tacrolimus is commonly prescribed to prevent transplant rejection and manage autoimmune disorders; however, it can cause severe nephrotoxicity and hepatotoxicity. Previous research has highlighted the protective role of ellagic acid (EA) against tacrolimus-induced toxicity. Objectives: This study aimed to evaluate the protective effects of EA against tacrolimus-induced hepatorenal toxicity in Wistar rats. Methods: In this experimental study, 24 male Wistar rats (200 ± 20 g, 8 weeks old) were randomly assigned to four groups (n = 6 each): the control group received intraperitoneal normal saline once daily; the tacrolimus group received tacrolimus 1 mg/kg/day by intraperitoneal injection; the tacrolimus + EA group received tacrolimus plus oral EA 50 mg/kg/day; and the EA group received oral EA 50 mg/kg/day. After 28 days, serum levels of ALT, AST, ALP, BUN, and creatinine were measured, along with oxidative stress indicators, including malondialdehyde (MDA), total antioxidant capacity (TAC), thiol proteins (GSH), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Histopathological analyses of liver and kidney tissues were also performed. Group comparisons were conducted using one-way ANOVA, Welch ANOVA, or the Kruskal-Wallis test, as appropriate, followed by post hoc corrections for multiple comparisons. Statistical significance was set at P < 0.05. Results: Tacrolimus administration induced significant hepatorenal toxicity and oxidative stress compared with the control group, as evidenced by marked increases in serum AST (153.50 ± 13.35 vs. 83.50 ± 1.78 U/L, P = 0.006), creatinine (1.31 ± 0.04 vs. 0.42 ± 0.01 mg/dL, P = 0.002), and MDA (22.26 ± 1.05 vs. 10.30 ± 0.29 nmol/mL, P < 0.001). Co-treatment with EA significantly attenuated tacrolimus-induced oxidative stress, reducing MDA to 15.67 ± 0.73 (P = 0.001) and restoring GSH to 3.96 ± 0.31 µmol/L (P = 0.007), compared with the tacrolimus group. Conclusions: Ellagic acid exerts protective effects against tacrolimus-induced hepatorenal toxicity by reducing lipid peroxidation and enhancing antioxidant defenses, suggesting its potential as an adjuvant therapy for patients receiving tacrolimus.en
DOIhttps://doi.org/10.5812/semj-167211en
URIhttps://brieflands.com/journals/semj/articles/167211en
KeywordEllagic Aciden
KeywordTacrolimusen
KeywordLiveren
KeywordKidneyen
KeywordHepatotoxicityen
KeywordNephrotoxicityen
KeywordRaten
PublisherBrieflandsen
TitleEllagic Acid Mitigates Hepato-renal Toxicity Induced by Tacrolimus in Wistar Ratsen
TypeResearch Articleen

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