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Alpha-tocopherol ameliorates nephrotoxicity associated with the use of colistin in rabbits
Zarafshan Bader1, Akbar Waheed2, Salman Bakhtiar3
1Pharmacology Department, Foundation University Medical College, DHA 1, Islamabad, Pakistan.
Abstract:
The alarming rise in the rate of multi drug resistant, life threatening gram negative infections has brought renaissance in the use of Colistin for last two decades. The major constraint in its utilization is its nephrotoxicity. Therefore it is being underused which is favoring the development of resistance. This study assesses the prevention of nephrotoxicity associated with high and low toxic doses of Colistin by alpha-tocopherol. Thirty rabbits were randomly divided into five groups. Baseline serum urea, creatinine and electrolytes were estimated. A loading dose of colistin was given in the form of infusion followed by I.M injections for six days. In the preventive groups α-tocopherol was additionally given orally for two weeks. Rabbits were sacrificed 24 hours after the last dose. The kidney slides graded and statistically analyzed using "chi square". The results of serum analysis were compared using one way analysis of variance followed by post hoc tukey test. There was marked nephrotoxicity in high toxic group where as in low toxic group mild nephrotoxicity was evident. Alpha-tocopherol attenuated the renal insult in both the toxic groups. As damage induced by colistin is oxidative in nature, thus it was concluded that the protection offered by α- tocopherol is due to its antioxidant activity.
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