Nephrotoxicity of Therapeutic Dose of Dihydroartemisinin-Piperaquine Phosphate in Male and Female Animals

Mutiu Adewunmi Alabi, Fatai A. Kareem, Fatai Akinwunmi3, Ayodeji O. Obatoye

Abstract


Dihydroartemisinin-piperaquine phosphate (DHAPP) is an artemisinin based combined therapy and is very effective in treating malaria in areas of high resistance to conventional malaria. The present study investigates the toxicological effects of the use therapeutic dose of DHAPP in male and female rats. Thirty adult Wister rats of both sexes weighing between 180 and 210 g were grouped into three consisting of 5 males and 5 females per group. The control group was orally administered with normal saline, the test and recovery groups were given body weight 15.4 mg/kg of DHAPP orally for three days after which the recovery group were allowed to recover from the drug’s effect for another three days. The blood samples were collected through cardiac puncture into heparinised tubes centrifuged at 5000 rpm for 10 minutes. The kidney were also removed, weighed, blotted dry and homogenised. The supernatant of each of the plasma and kidney was kept in clean bottles, stored at -4oC and were used for kidney function and histological analysis.An increment was observed in the protein, creatinine and urea levels in the plasma while in the kidney, the levels decreased. In the plasma and kidney, all the biochemical parameters were observed to return to normal when the animals were left to recover. Sex related differences were noted in most of the groups in the plasma and kidney of the enzyme activities. Histological examination also revealed an intoxication of the kidney cell of the rats.It could therefore be inferred from these results that increases in protein, creatinine and urea levels in the blood plasma showed the possibility of abnormality in the renal system when the drug was administered. It is therefore recommended that the drug should be administered with caution.


Keywords


Dihydroartemisinin-piperaquine phosphate (DHAPP), artemisinin, antimalarial, therapeutic dose

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References


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