Renal toxicity of methylprednisolone in male Wistar rats and the potential protective effect by boldine supplementation

Abstract

Objective: Intravenous corticosteroids, methylprednisolone (MPL), which is one of the drugs that induce glomerular kidney diseases, when used for a long time at high dose by doctors to treat acute renal inflammation, promote the development of reactive oxygen species (ROS)-induced renal toxicity. This study investigated the role of boldine, a natural antioxidant with anti-apoptotic and anti-inflammatory properties, against MPL-induced renal toxicity in male Wistar rats. Methods: 120 rats were divided into eight equal groups as follows: G1 (control), G2, 3, and 4 (rats orally administered 5, 10, and 50 mg boldine/kg/day; respectively, for 28 days), G5 (rats intramuscularly injected with 100 mg MPL/kg 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 increase in body weight, blood glucose, and urea levels, as well as a decrease in albumin level in serum. Oxidative stress markers levels increased at all times, and gene expression of anti-oxidant enzymes increased at 24 h. According to immunohistochemistry, there was a considerable increase in P53 and TNF-α levels following MPL therapy. The cell death DNA assays revealed detectable necrosis and apoptosis, induced by MPL treatment. Conclusions: Oral administration of boldine has a modulatory protective, anti-oxidant, anti-apoptotic, and anti-inflammatory effect against free radicals.

Keywords

• Methylprednisolone
• Renal toxicity
• Oxidative stress
• DNA damage
• Boldine
• Anti-oxidant properties