Amelioration of cisplatin-induced nephrotoxicity in rats by tetramethylpyrazine, a major constituent of the chinese herb ligusticum wallichi

B. H. Ali, M. Al-Moundhri, M. Tag Eldin, A. Nemmar, S. Al-Siyabi, K. Annamalai

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Abstract

Nephrotoxicity of the anticancer drug, cisplatin (CP) involves enhanced renal generation of reactive oxygen metabolites and lipid peroxidation caused by decreased levels of antioxidants and antioxidant enzymes. Tetramethylpyrazine (TMP) is known to act as a strong antioxidant. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of TMP on CP nephrotoxicity in rats. TMP was given orally at a dose of 80 mg kg-1 day-1 for 7 days. Some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg on Day 6 of treatment. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained. Nephrotoxicity was assessed biochemically by measuring creatinine and urea in serum, reduced glutathione (GSH) concentration in renal cortex, by urinalysis, and histopathologically by light microscopy. CP significantly increased the concentration of urea and creatinine (P <0.05) by about 128% and 170%, respectively; increased urine volume and N-acetyl-p-D-glucosaminidase (NAG) activity; and significantly decreased osmolality and protein concentrations. CP treatment reduced GSH by about 34% (P<0.05) and superoxide dismutase (SOD) and total antioxidant activity (TOX) by about 28% and 21%, respectively (P <0.05). TMP pretreatment significantly mitigated all of these effects. Sections from saline-and TMP-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly reduced when CP was given after pretreatment with TMP. CP cortical concentration was not significantly altered by TMP treatment. The results suggest that TMP ameliorated the histological, physiological, and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, TMP may potentially be useful as a nephroprotective agent.

Original languageEnglish
Pages (from-to)891-896
Number of pages6
JournalExperimental Biology and Medicine
Volume233
Issue number7
DOIs
Publication statusPublished - Jul 2008

Fingerprint

Ligusticum
Cisplatin
Rats
Antioxidants
Kidney
Urea
Creatinine
Urine
tetramethylpyrazine
Hexosaminidases
Urinalysis
Therapeutics
Metabolites
Intraperitoneal Injections
Osmolar Concentration
Toxicology
Lipid Peroxidation
Superoxide Dismutase
Optical microscopy
Glutathione

Keywords

  • Cisplatin
  • Nephrotoxicity
  • Tetramethylpyrazine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Amelioration of cisplatin-induced nephrotoxicity in rats by tetramethylpyrazine, a major constituent of the chinese herb ligusticum wallichi. / Ali, B. H.; Al-Moundhri, M.; Eldin, M. Tag; Nemmar, A.; Al-Siyabi, S.; Annamalai, K.

In: Experimental Biology and Medicine, Vol. 233, No. 7, 07.2008, p. 891-896.

Research output: Contribution to journalArticle

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abstract = "Nephrotoxicity of the anticancer drug, cisplatin (CP) involves enhanced renal generation of reactive oxygen metabolites and lipid peroxidation caused by decreased levels of antioxidants and antioxidant enzymes. Tetramethylpyrazine (TMP) is known to act as a strong antioxidant. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of TMP on CP nephrotoxicity in rats. TMP was given orally at a dose of 80 mg kg-1 day-1 for 7 days. Some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg on Day 6 of treatment. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained. Nephrotoxicity was assessed biochemically by measuring creatinine and urea in serum, reduced glutathione (GSH) concentration in renal cortex, by urinalysis, and histopathologically by light microscopy. CP significantly increased the concentration of urea and creatinine (P <0.05) by about 128{\%} and 170{\%}, respectively; increased urine volume and N-acetyl-p-D-glucosaminidase (NAG) activity; and significantly decreased osmolality and protein concentrations. CP treatment reduced GSH by about 34{\%} (P<0.05) and superoxide dismutase (SOD) and total antioxidant activity (TOX) by about 28{\%} and 21{\%}, respectively (P <0.05). TMP pretreatment significantly mitigated all of these effects. Sections from saline-and TMP-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly reduced when CP was given after pretreatment with TMP. CP cortical concentration was not significantly altered by TMP treatment. The results suggest that TMP ameliorated the histological, physiological, and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, TMP may potentially be useful as a nephroprotective agent.",
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