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Aim: To determine the effects of antimalaria and antheminthic drugs combination in the incidence of histopathological alteration and biochemical modulations in liver and kidney of albino rats.
Place and Duration of Study: The study was undertaken at the Zoology Department University of Lagos Akoka Lagos Nigeria.
Methodology: A total of twenty (25) Male adult albino rats of 13-15 weeks old were divided into 5 groups of 5 rats each and daily oral administration of human therapeutic doses of praziquantel (PZQ 50 mg/kg body weight) separate and in combination with ivermectin (IVM 0.4 mg/kg body weight), albendazole (ALB 15 mg/kg body weight) and Artemether-lumefanthrine (ACT 140 mg/kg body weight) was administered with the group which serve as the control receiving 1ml distilled water. Toxic effects due to these treatments were investigated using histopathological, biochemical and mutagenic indices at day 8th and 15th of the study.
Results: Biochemical assessment revealed significant reduction in AST, ALT, ALP and potassium in the treatment group compared to the control. Increase in the level calcium, Albumin and bicarbonate were also observed in treatment groups. Histopathological assessment of the liver showed a general incidence of focal inflammation along the portal tract area, but did not show any differential severity across treatment groups except for single PZQ treatment group which were characterized by fatty infiltration. A general occurrence of mesangial damage and glomerula injury was observed in kidney tissues. Renal lesions were more severe in single PZQ + IVM treatment groups while mild lesions characterized renal tissue from PZQ+ACT treatment groups. Mutagenic effects as indicated by the high incidence of sperm head abnormalities was recorded across combination treatments especially in PZQ+ IVR and PZQ+ ACT groups.
Conclusion: Findings suggest that combination therapies are synergistic and could result in nephrotoxicity, antidiuretic effects, dehydration and mutagenicity at human therapeutic doses.
Allarakhia M. Open-source approaches for the repurposing of existing or failed candidate drugs: Learning from and applying the lessons across diseases. Drug Des. Dev. Ther, 2013;7:753-66.
Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, Savioli. Control of neglected tropical diseases New England Journal of Medicine. 2007;357:1018-1027.
Hotez PJ, Brindley PJ, Bethony JM, Kong CH, Pearce EJ, Jacobson J. Helminth infections: The great neglected tropical disease. The Journal of Clinical Investigation. 2008;118:1311-1321.
WHO. Global Report on Antimalarial drug Efficacy and Drug Resistance; 2010.
Garcia HH. Antiparasitic drugs in neurocysticercosis: Albendazole or praziquantel? Expert Review of Anti-infective Therapy. 2008;6:295-298.
Andrew KT, Fisher G, Skinner-Adams TS. Drug repurposing and human parasitic protozoan diseases. International Journal for parasitology: Drugs and Drug Resistance, 2014;4:95-111.
Lameire NH, Flombaum CD, Moreau D, Ronco C. Acute renal failure in cancer patients. Annals of Medicine. 2005;37: 13-25.
Ramachandran R, Kakar S. Histological patterns in drug-induced liver disease. Journal of Clinical Pathology. 2009;62: 481-492.
Decloedt E, Maartens G. Drug-induced renal injury: Main article. CME: Your SA Journal of CPD: Pharmacology. 2011;29: 252-255.
Markowitz GS, Perazella MA. Drug-induced renal failure: A focus on tubulointerstitial disease. Clinica Chimica Acta. 2005;351:31-47.
Vickers AE, Fisher RL. Organ slices for the evaluation of human drug toxicity. Chemico-biological Interactions. 2004; 150:87-96.
Ismail S, Botros A, Metwally S, William A, Farghally L, Tao TA, et al. Resistance to praziquantel: Direct evidence from Schistosoma mansoni isolated from Egyptian villagers Am. Soc. Trop. Med. Hyg. 1999;60:932-935.
Arise R, Malomo S. Effects of ivermectin and albendazole on some liver and kidney function indices in rats. African Journal of Biochemistry Research. 2009; 3:190-197.
Bitto II, Gemade M. Afri. J. Biomed. Res. 2001;9:199-209.
Doumas BT, Watson WA, Biggs HG. Albumin standards and measurement of serum-albumin with bromocresol green. Clin. Chim. Acta. 1971;31:87-92.
Young RR, Asbury AK, Corbett JL, Adams RD. Pure pandyautonomia with recovery: Description and discussion of diagnostic criteria. Brain. 1975;98:613-36.
Wyrobek A, Bruce W. Chemical induction of sperm abnormalities in mice. Proceedings of the National Academy of Sciences of the United States of America. 1975;72:4425-4429.
Loh AH, Cohen AH. Drug-induced kidney disease-pathology and current concepts. Ann Acad Med Singapore. 2009;38:240-250.
Perazella MA. Drug-induced nephropathy: An update. Expert Opinion on Drug Safety. 2005;4:689-706.
Yamasaki K, Chuang VTG, Maruyama T, Otagiri M. Albumin–drug interaction and its clinical implication. Biochimica et Biophysica Acta (BBA)-General Subjects. 2013;1830:5435-5443.
Galla JH. IgA nephropathy. Kidney international. 1995;377-387.
Sahay M, Sahay R. Hyponatremia: A practical approach. Indian Journal of Endocrinology and Metabolism. 2014;18: 760.
Hennessey IA, Jappa AG. Arterial blood gases made easy, Elsevier health Sciences; 2007.
Stratta P, Lazzarich E, Canavese C, Bozzola C, Monga G. Ciprofloxacin crystal nephropathy. American Journal of Kidney Diseases. 2007;50:330-335.
Liedke C, Luedde T, Sauerbruch T, Scholten D, Streetz K, Tacke F, et al. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis & Tissue Repair. 2013;6(1).
Harada Y, Hatanaka K, Kawamura M, Saito M, Ogino M, Majima, et al. Role of prostaglandin H synthase-2 in prostaglandin E 2 formation in rat carrageenin-induced pleurisy. Prostaglandins. 1996;51:19-33.
Murray KF, Hadzic N, Wirth S, Bassett M, Kelly D. Drug-related hepatotoxicity and acute liver failure. Journal of Pediatric Gastroenterology and Nutrition. 2008;47: 395-405.
Kirchain and Allen; 2014.
Leo MA, Lieber CS. Alcohol, Vitamin A, and β-carotene: Adverse interactions, including hepatoxicity and carcinogenicity. The American Journal of Clinical Nutrition. 1999;69:1071-1085.
Lee WM. Acute liver failure. New England Journal of Medicine. 1993;329:1862-1872.
Konig S, Schenk M, Sick C, Holm E, Heubner C, Weiss A, Konig, et al. Fatal liver failure associated with valproate therapy in a patient with Friedreich’s disease: Review of valproate hepatotoxicity in adults. Epilepsia. 1999; 40:1036-1040.
Ali MH, Abramson FP, Fetterolf DD, Cohn VH. Metabolism studies of the antischistosomal drug praziquantel using tandem mass spectrometry: Distribution of parent drug and ten metabolites obtained from control and schistosome-infected mouse urine. Biological Mass Spectrometry. 1990;19:186-190.
Meister I, Kovac J, Duthaler U, Odermatt P, Huwyler J, Vanobberghen F, et al. Pharmacokinetic study of praziquantel enantiomers and its main metabolite R-trans-4-OH-PZQ in plasma, blood and dried blood spots in Opisthorchis viverrini infected patients. PLoS Neglected Tropical Diseases. 2016;10:e0004700.
Aleska K, Matsell D, Krausz K, Gelboin H, ITO S, Koren G. Cytochrome P450 3A and 2B6 in the developing kidney: implications for ifosfamide nephrotocity. Paediatric Nephrology. 2005;20:872-885.
Cummings BS, Schnellmann RG. Pathophysiology of nephrotoxic cell injury. Diseases of the kidney and urinary tract. Philadelphia Lippincott Willams & Wilkins. 2001;1071-1091.
Kaloyanides G, Bismans J, Debroe M. Antibiotic and immunosuppression-related renal failure. Disease of the kidney and Urogenital Tract, edited by Schrier RW, Philadelphia PA, Lippincott Williams & Wilkinson. 2001;1137-1174.
Lucena MI, Andrade RJ, Cabello MR, Hidalgo R, Gonzalez-Correa JA, De La Cuesta FS. Aminoglycoside-associated nephrotoxicity in extrahepatic obstructive jaundice. Journal of Hepatology. 1995; 22:189-196.
Aduloju R, Otubajo O, Odeigah P. An in vivo assay of the mutagenic potential of praziquantel (PZQ) using sperm head abnormality test. J Hum Ecol. 2008;23: 59-63.
Frohberg GH. Result of toxicological studies on praziquantel. Arzneimittel-Forschung. 1984;34:1137-1144.
WHO. Report of the WHO Informal Consultation on the Use of Praziquantel during Pregnanc; 2003.
Otubanjo O, Mosuro A. An in vivo evaluation of induction of abnormal sperm morphology by some anthelmintic drugs in mice. Mutation Research/ Genetic Toxicology and Environmental Mutagenesis. 2001;497: 131-138.