Volume 16, Issue 37, January - June, 2022

Hepatotoxic impact of desloratadine/dihydroartemisinin/piperaquine on healthy and parasitized mice

Georgewill UO¹, Adikwu E², Ebong NO^1♦

¹Department of Pharmacology, Faculty of Basic Clinical Sciences, University of Port Harcourt, Rivers State, Nigeria
²Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria.

^♦Corresponding author
Department of Pharmacology, Faculty of Basic Clinical Sciences, University of Port Harcourt, Rivers State, Nigeria

ABSTRACT

Background: Desloratadine/dihydroartemisinin/piperaquine (DL/D/P) can be used for malaria treatment, but its safety assessment is imperative. Objective: To evaluate its hepatotoxic effect on healthy and Plasmodium berghei-infected mice. Method: Fifty-four adult Swiss albino mice (25-30g) were used. The mice, n=6/group were inoculated with Plasmodium berghei (1 × 107 ) and treated with DL (5mg/kg), D/P (1.71/13.7mg/kg) and DL/D/P daily for 4 days, respectively. The healthy mice were treated with DL (5mg/kg), D/P (1.71/13.7mg/kg) and DL/D/P daily for 28 days, respectively. After drug treatment, the mice were weighed and anesthetized. Blood samples were collected and assessed for liver function indices. Liver samples were excised, weighed and evaluated for oxidative stress markers and histology. Results: DL, D/P and DL/D/P had no significant (p>0.05) effects on liver function parameters in parasitized mice when compared to control. DL, D/P and DL/D/P significantly decreased body weight and significantly increased liver weight in healthy mice at p<0.05, p<0.05, and p<0.01, respectively when compared to control. Serum aminotranferases, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase and bilirubin levels increased significantly while total protein and albumin levels decreased significantly in healthy mice treated with DL (p<0.05), D/P(p<0.01) and DL/D/P (p<0.001) when compared to control. Significantly decreased liver catalase, glutathione peroxidase superoxide dismutase, and glutathione with significantly increased malondialdehyde levels were observed in healthy mice treated with DL (p<0.05), D/P (p<0.01) and DL/D/P (p<0.001) when compared to control. DL/D/P produced hepatocyte necrosis in healthy mice. Conclusion: Malaria treatment with DL/D/P may be safe on the liver, but prolonged use may cause liver dysfunction.

Keywords: Dihydroartemisinin/piperaquine, Desloratadine, Plasmodium, Hepatotoxicity, Mice

Drug Discovery, 2022, 16(37), 36-44

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