Abrogation of cisplatin‐induced nephrotoxicity by emodin in rats

Abstract

Nephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen species in renal cortex, and emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions. Therefore, we tested here the possible ameliorative effect of emodin on CP nephrotoxicity in rats. Emodin was given orally (10 mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Five days after CP treatment, rats were killed, and blood and urine samples, and kidneys were collected for the assessment of histopathological renal damage and apoptosis, and for biochemical estimation of creatinine and urea concentrations in plasma and urine, several cytosolic antioxidant enzyme activities in kidneys, and urinalyses. CP significantly increased the concentrations of urea and creatinine, and decreased creatinine clearance. It also significantly reduced cortical glutathione concentration and the activity of superoxide dismutase. CP treatment significantly increased urine volume and N-acetyl-β-D-glucosaminidase activity and significantly decreased osmolarity and protein concentrations. Emodin treatment markedly and significantly mitigated all these effects. Sections from saline- and emodin-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with emodin. The concentration of CP in the cortical tissues was not significantly altered by emodin treatment. The results suggested that emodin had ameliorated CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies emodin may be considered a potentially useful nephroprotective agent.

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles

“…16,26 As shown in Table 2, rats given saline or TQ alone gained an increase in their body weight of about 16.5% and 18.6%, respectively (p < 0.05), while those receiving CP only lost 15.3%, and those given DEP only gained about 8.7% (p < 0.05, when compared to control). However, rats treated with CP together with TQ lost 11.5% of their bodyweight, while rats treated with DEP together with TQ gained only 0.6% of their body weight.…”

“…Kidney reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and total antioxidant capacity (TAC) were measured as described before. 16 …”

“…These include antioxidants, modulators of nitric oxide, diuretics, cytoprotective, and anti-apoptotic agents and others. 11,[14][15][16][17] However, none of these have been tested clinically in humans.…”

Diesel Exhaust Particles Induce Impairment of Vascular and Cardiac Homeostasis in Mice: Ameliorative Effect of Emodin

“…As cardiovascular toxicity of DEP is mediated, at least partially, by oxidative mechanisms [7], and emodin has protective or ameliorative effects against some experimental diseases and conditions involving inflammation and oxidative stress [9][10][11][12], we considered that it was of interest to evaluate the possible protective effect of emodin against DEP-induced cardiovascular complications in mice. To our knowledge, this is the first study on such an interaction.…”

“…Among these functional foods is emodin (1,3,8-trihydroxy-6-methylanthraquinone), which is an anthraquinone extracted from the root of the rhubarb plant (Rheum palmatum) that protects against oxidative stress in different models [9][10][11][12].…”