TY - JOUR

T1 - Antioxidants resveratrol and SkQ1 attenuate praziquantel adverse effects on the liver in Opisthorchis felineus infected hamsters

AU - Zaparina, Oxana

AU - Rakhmetova, Akbota S.

AU - Kolosova, Nataliya G.

AU - Cheng, Guofeng

AU - Mordvinov, Viatcheslav A.

AU - Pakharukova, Maria Y.

N1 - Publisher Copyright: © 2021 Elsevier B.V.

PY - 2021/8

Y1 - 2021/8

N2 - Anthelmintic praziquantel (PZQ) is the drug of the choice for opisthorchiasis, schistosomiasis and other trematodiases therapy for several decades. Despite its good therapeutic performance and effective control of trematode infections, PZQ has some shortcomings; its inability to counteract disease sequelae necessitates novel therapeutic strategies. Testing of antioxidants that have proven themselves in clinical practice, in combination with this anthelmintic drug, offers new opportunities for developing alternatives to PZQ monotherapy. The effects of two antioxidants combined with PZQ on histological parameters of liver tissue were evaluated in a hamster model of opisthorchiasis felinea. Liver pathology including the parenchyma state, accumulation of neutral lipids and 4-Hydroxy-2-nonenal as a lipid peroxidation product, biochemical characteristics of hamster blood serum, and mRNA expression of inflammation- and fibrogenesis-associated genes were determined. PZQ and opisthorchiasis caused liver accumulation of lipids and glycogen. The combination of PZQ with resveratrol (RSV) or 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) significantly reduced hepatocyte changes (P = 0.009 and P = 0.009, respectively, Mann–Whitney U test) as compared with infected hamsters treated only with PZQ. RSV and SkQ1 significantly reduced cholangiocyte hyperplasia, bile duct proliferation, fibrosis, and lipid droplet and glycogen granule accumulation. The downregulation of 4-hydroxynonenal was also observed. The combinations of the anthelmintic drug with antioxidants RSV and SkQ1 ameliorate host oxidative stress and mitigate adverse effects of PZQ on hepatic parenchyma. The use of drug combinations may improve the action of standard anthelmintic agents, such as PZQ, which still remains the most effective agent against adult trematodes.

AB - Anthelmintic praziquantel (PZQ) is the drug of the choice for opisthorchiasis, schistosomiasis and other trematodiases therapy for several decades. Despite its good therapeutic performance and effective control of trematode infections, PZQ has some shortcomings; its inability to counteract disease sequelae necessitates novel therapeutic strategies. Testing of antioxidants that have proven themselves in clinical practice, in combination with this anthelmintic drug, offers new opportunities for developing alternatives to PZQ monotherapy. The effects of two antioxidants combined with PZQ on histological parameters of liver tissue were evaluated in a hamster model of opisthorchiasis felinea. Liver pathology including the parenchyma state, accumulation of neutral lipids and 4-Hydroxy-2-nonenal as a lipid peroxidation product, biochemical characteristics of hamster blood serum, and mRNA expression of inflammation- and fibrogenesis-associated genes were determined. PZQ and opisthorchiasis caused liver accumulation of lipids and glycogen. The combination of PZQ with resveratrol (RSV) or 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) significantly reduced hepatocyte changes (P = 0.009 and P = 0.009, respectively, Mann–Whitney U test) as compared with infected hamsters treated only with PZQ. RSV and SkQ1 significantly reduced cholangiocyte hyperplasia, bile duct proliferation, fibrosis, and lipid droplet and glycogen granule accumulation. The downregulation of 4-hydroxynonenal was also observed. The combinations of the anthelmintic drug with antioxidants RSV and SkQ1 ameliorate host oxidative stress and mitigate adverse effects of PZQ on hepatic parenchyma. The use of drug combinations may improve the action of standard anthelmintic agents, such as PZQ, which still remains the most effective agent against adult trematodes.

KW - Antioxidants

KW - Experimental opisthorchiasis

KW - Hepatocyte changes

KW - Opisthorchis felineus

KW - Praziquantel

KW - Resveratrol

KW - SkQ1

KW - Cricetinae

KW - Antioxidants/pharmacology

KW - Resveratrol/pharmacology

KW - Liver/drug effects

KW - Praziquantel/adverse effects

KW - Oxidative Stress/drug effects

KW - Lipid Peroxidation/drug effects

KW - Animals

KW - Opisthorchis/drug effects

KW - Anthelmintics/adverse effects

KW - Drug Combinations

UR - http://www.scopus.com/inward/record.url?scp=85107271367&partnerID=8YFLogxK

U2 - 10.1016/j.actatropica.2021.105954

DO - 10.1016/j.actatropica.2021.105954

M3 - Article

C2 - 33979641

AN - SCOPUS:85107271367

VL - 220

JO - Acta Tropica

JF - Acta Tropica

SN - 0001-706X

M1 - 105954

ER -