TY - JOUR
T1 - Abrogation of cisplatin-induced nephrotoxicity by emodin in rats
AU - Ali, Badreldin H.
AU - Al-Salam, Suhail
AU - Al Husseini, Isehaq S.
AU - Al-Lawati, Intisar
AU - Waly, Mostafa
AU - Yasin, Javed
AU - Fahim, Mohamed
AU - Nemmar, Abderrahim
PY - 2013/4
Y1 - 2013/4
N2 - 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 (10mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6mg/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.
AB - 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 (10mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6mg/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.
KW - Cisplatin
KW - Emodin
KW - Nephrotoxicity
KW - Rats
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U2 - 10.1111/j.1472-8206.2011.01003.x
DO - 10.1111/j.1472-8206.2011.01003.x
M3 - Article
C2 - 22044459
AN - SCOPUS:84874384385
SN - 0767-3981
VL - 27
SP - 192
EP - 200
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
IS - 2
ER -