Potential Effects of Boldine on Oxidative Stress, Apoptosis, and Inflammatory Changes Induced by the Methylprednisolone Hepatotoxicity in Male Wistar Rats

Boldine 对雄性 Wistar 大鼠甲基强的松龙肝毒性引起的氧化应激、细胞凋亡和炎症变化的潜在影响

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作者:Esraa Shuker, Manal Farhood, Ghofran Al-Qudaihi, Dalia Fouad

Background

Synthetic glucocorticoid therapeutic agent methylprednisolone (MPL), when used for an extended period of time at high dose, promotes the development of reactive oxygen species (ROS)-induced liver toxicity. This study investigated the role of boldine, a natural antioxidant with anti-apoptotic and anti-inflammatory properties, against MPL-induced hepatoxicity in male Wistar rats.

Conclusions

Oral administration of boldine has a modulatory protective, antioxidant, and anti-apoptotic effect against free radicals.

Methods

120 rats were divided into eight equal groups: G1 (control), G2, 3, and 4 (rats orally administered 5, 10, and 50 mg boldine/kg b.w./day; respectively, for 28 days), G5 (rats intramuscularly injected with 100 mg MPL/kg b.w. only on the last three days), G6, 7, and 8 (rats administered boldine + MPL). After the last MPL injection, rats were sacrificed at intervals of 1, 24, and 48 h.

Results

There was a significant decrease in WBCs, RBCs count, and HGB levels, as well as an increase in PLT count, ALT, AST, TG, and LDL levels, and a decrease in HDL level in serum. Oxidative stress markers levels increased at all times, and gene expression of antioxidant enzymes increased at 24h. Immunohistochemical analysis revealed that cytochrome c levels significantly increased after MPL treatment. The COMET assay revealed detectable DNA lesions. There was no immune reactivity of IL-6 expressions as an inflammatory response marker. Conclusions: Oral administration of boldine has a modulatory protective, antioxidant, and anti-apoptotic effect against free radicals.

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