Abstract
Cisplatin (CP) as a potent chemotherapeutic agent is restricted due to its hepatotoxicity, nephrotoxicity, and multiple organ toxicity. The current study investigates the possible mechanisms responsible for the hepatorenal protective effects of ginger extract (GE) against cisplatin-induced hepatorenal toxicity in rats. Thirty-two male albino rats (240–250 g) were divided into four equal groups (n = 8) as follows: control group (single i.p. saline dose 7.5 ml/kg at the 15th day of the study), CP-treated group (7.5 mg/kg single i.p. injection of CP at the 15th day of the study), GE-treated group (500 mg/kg/ p.o daily for 20 days), and GE + CP-treated group (GE 500 mg/kg/day, p.o daily for 15 days prior to CP injection and 5 days after CP injection). At day 21st of the experiment, blood samples were collected, and serum was isolated for biochemical assessments. Then, rats were euthanized, and hepatic and renal tissues were collected for tissue biochemical parameters, histopathology, and immunohistochemistry evaluations. Cisplatin-injected rats showed marked alterations in the serum liver and kidney functions, oxidant/antioxidant biomarkers, pro-inflammatory cytokines; tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and anti-inflammatory cytokine; interleukin-10 (IL-10). CP also induced overexpression of oxidative (INOS) and apoptotic (caspase-3) immunohistochemical markers in hepatic and renal tissues. Conversely, the combining administration of ginger extract before, with, and after CP treatment ameliorated the aforementioned biochemical, pathological, and immunohistochemical adverse effects induced by CP. In conclusion, ginger extract has protective effects against CP adverse effects, possibly via its antioxidant, anti-inflammatory, and anti-apoptotic properties.
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The authors would like to thank the laboratory technician at the Department of Veterinary Pathology, Faculty of Veterinary Medicine, for their great help during preparation of histopathological slides.
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All the listed authors have made substantial contributions to the research design and acquisition, analysis, or interpretation of the data. ET and AE performed histopathology and IHC examination; GE performed chemical examination. All the authors have shared in writing the manuscript and approved the final submitted version.
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Tahoun, E., Elgedawy, G. & El-Bahrawy, A. Cytoprotective effect of ginger extract on cisplatin-induced hepatorenal toxicity in rats via modulation of oxidative stress, inflammation and apoptosis: histopathological, biochemical and immunohistochemical study. Comp Clin Pathol 30, 647–663 (2021). https://doi.org/10.1007/s00580-021-03256-7
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DOI: https://doi.org/10.1007/s00580-021-03256-7