Hepatoprotective effect of ferulic acid and/or low doses of γ-irradiation against cisplatin-induced liver injury in rats

Abstract

The therapeutic efficacy of cisplatin (CIS) is limited owing to its hepatotoxic side effects. The current study aimed to investigate the protective impact of ferulic acid (FA) and low-doses of γ-irradiation (LDR) against CIS-prompted hepatotoxicity in rats. Adult male Swiss albino rats were divided into eight groups: untreated group; FA, LDR, and CIS treated groups; and combinations of one or more of the above treatments. Post-treatment analyses included measuring redox markers like SOD and CAT activity, NO free radical content, and lipid peroxidation in liver tissue. Serum aminotransferase activities were also determined. Additionally, gene transcript levels of liver NF-ҡB-P65, caspase-1, COX-2, and IL-1β were quantified. Moreover, immunohistochemistry for caspase-3 and histopathological examinations were estimated in liver tissue. Our findings revealed increased levels of oxidative stress along with a significant reduction in anti-oxidative responses and a significant increase in serum aminotransferase activities in the CIS-intoxicated group. A similar increase was also observed in COX-2 and IL-1β transcript levels and caspase-3 enzyme activity, besides a decrease in transcript levels of NF-ҡB-p65 and caspase-1, indicating an overall inflammatory trend and an increase in the apoptotic shift. The co-administration of FA and/or treatment with LDR has ameliorated the hepatotoxic effect induced by CIS. The histopathological investigation of liver tissues confirmed this ameliorating action of these adjuvant therapies against CIS toxicity. In conclusion, it is plausible to suggest that the hepatoprotective effects of co-administration of FA and/or LDR against CIS-induced hepatotoxicity are attributed to the possession of anti-oxidative, anti-inflammatory, and anti-apoptotic capabilities.

Therapeutic Promises of Ferulic Acid and its Derivatives on Hepatic damage Related with Oxidative Stress and Inflammation: A Review with Mechanisms

“…[58][59][60][61][62] Results of various non-clinical and preclinical tests demonstrated that FA and its different derivatives have remarkable antioxidant activity as the chemicals increase the activity of antioxidant enzymes and reduce oxidative stress. [63,64] In a study by (Esmat et al, 2022), it was stated that FA at the dose of 40 mg/kg significantly reduced oxidative stress with enhancing the activity of antioxidants such as SOD and CAT in the cisplatin-induced injured liver of rats. [63] Another study by (Ahmadipour et al, 2021) also reported that FA at doses of 10 and 20 mg/kg remarkably reduced oxidative stress in isoniazid- Review induced hepatotoxic rats by reducing the oxidative stressrelated marker MDA and increasing the level of antioxidant enzymes (e. g. SOD, CAT, and GPx).…”

“…[63,64] In a study by (Esmat et al, 2022), it was stated that FA at the dose of 40 mg/kg significantly reduced oxidative stress with enhancing the activity of antioxidants such as SOD and CAT in the cisplatin-induced injured liver of rats. [63] Another study by (Ahmadipour et al, 2021) also reported that FA at doses of 10 and 20 mg/kg remarkably reduced oxidative stress in isoniazid- Review induced hepatotoxic rats by reducing the oxidative stressrelated marker MDA and increasing the level of antioxidant enzymes (e. g. SOD, CAT, and GPx). [65] FA (25-100 mg/kg) also reduced oxidative stress induced by methotrexate (20 mg/kg) by boosting the activity of antioxidant enzymes (e. g., GSH, CAT, SOD, and GPx), resulting in an improvement of hepatic damage.…”

“…[76] Treatment with FA at the dose of 40 mg/kg significantly reduced apoptotic cell death in cisplastin-induced hepatotoxic rats by diminishing the activity of caspase-3. [63] Another study by (Wu et al, 2022) stated that FA treatment remarkably increased the Bax/Bcl2 ratio while decreasing caspase-3 expression in acetaminophen-induced hepatotoxic cells. [77] MFA also reduced apoptotic death in hepatic injuries caused by toxic substances.…”

“…Results of various non‐clinical and preclinical tests demonstrated that FA and its different derivatives have remarkable antioxidant activity as the chemicals increase the activity of antioxidant enzymes and reduce oxidative stress [63,64] . In a study by (Esmat et al., 2022), it was stated that FA at the dose of 40 mg/kg significantly reduced oxidative stress with enhancing the activity of antioxidants such as SOD and CAT in the cisplatin‐induced injured liver of rats [63] .…”

Cistus albidus L.—Review of a Traditional Mediterranean Medicinal Plant with Pharmacological Potential

“…6 Carvacrol monocyclic monoterpene alcohol 🌱✿ [49] antibacterial (64); antifungal [63]; antioxidant [64]; anticancer [65]; anti-inflammatory, analgesic [66]; antiobesity [67]; hepatoprotective [68]; spasmolytic [69]; vasorelaxant [70]; 7 β-Cyclocitral oxygenated monocyclic monoterpene 🌱 [53] n/a [12] antioxidant [199]; antimicrobial [200]; anti-inflammatory [201]; neuroprotective [202]; antiviral [203]; antiallergic [204]; hepatoprotective [205]; anticancer [206]; antithrombotic [207]; antidiabetic [208];…”