THYMOQUINONE AND ALBENDAZOLE AS UNCOMPETATIVE INHIBITORS OF GLUTATHIONE-S-TRANSFERASE IN Moniezia expansa: IMPLICATIONS FOR ANTHELMINTHIC THERAPY
DOI:
https://doi.org/10.48165/abr.2024.26.01.55Keywords:
Albendazole, glutathione-S-transferase, Moniezia expansa, cestode, thymoquinoneAbstract
The infection of Moniezia expansa is common among sheep and goat in the Indian sub-continent, and little is known about their detoxification ability. Therefore, in this study specific activity of glutathione-S-transferase (GST), along with its kinetic parameters like Km, Vmax, pH and temperature optima were investigated before and after treatment of worms with thymoquinone (TQ), and albendazole (ALBZ). Worms were collected from the infected small intestine of goats (Capra hircus) washed in Hanks' medium and incubated separately in RPMI 1640 medium with and without 120 µM TQ and ALBZ at 37ºC for 4 h. The specific activity of GST in the somatic extract of M. expansa was found to be 59.12 µ mole min-1 mg-1 protein. The optimum temperature and pH were found to be 25˚C and 6.5, respectively. It was observed that the rate of reaction increased with the increasing concentration of both GSH and CDNB; and maximum velocity (Vmax) of enzyme was recorded at 2 mM concentration for both the substrates. The Km value was higher while Vmax was lower in both TQ and ALBZ treated worms than control, indicating that both TQ and the ALBZ act as uncompetitive inhibitors of GST in M. expansa and appeared to be equally effective in inhibiting the GST activity, possibly through conformational changes of enzyme. This type of inhibition may greatly affect the detoxification ability of the worms and, therefore, their survival in the host; hence, GST of M. expansa could be exploited for therapeutic intervention and thymoquinone could be further tested at the in vivo level for dose standardization and field application.
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Brophy, P.M. and Pritchard, D.I. 1994. Parasitic helminth glutathione S-transferases: An update on their potential as targets for immuno-and chemo-therapy. Experimental Parasitology, 79: 89-96.
Brophy, P.M., Southan, C. and Barrett, J. 1989. Glutathione transferases in the tapeworm Moniezia expansa. Biochemical Journal, 262: 939-946.
Chen, W.Q., Liu, S.S., Cheng, C., Cui, J., Wang, Z.Q. and Zhang, X. 2022. Molecular characteristics of glutathione transferase gene family in a neglect medical Spirometra tapeworm. Frontiers in Veterinary Science, 9: 1035767. [https://doi.org/10.3389/fvets.2022.1035767].
Chiumiento, L. and Bruschi, F. 2009. Enzymatic antioxidant systems in helminth parasites.
Parasitology Research, 105: 593-603.
Douch, P.G.C. and Buchanan, L.L. 1978. Glutathione conjugation of some xenobiotics by Ascaris suum and Moniezia expansa. Xenobiotica, 8: 171-176.
Farhat, F., Wasim, S. and Abidi, S.M.A. 2022. Antihelminthic effect of thymoquinone against biliary amphistome, Gigantocotyle explanatum. Experimental Parasitology, 243: 108421. [https://doi.org/10.1016/j.exppara.2022.108421].
Fissiha, W. and Kinde, M.Z. 2021. Anthelmintic resistance and its mechanism: A review. Infection and Drug Resistance, 14: 5403-5410. [https://doi.org/10.2147/IDR.S332378].
Habig, W.H., Pabst, M.J. and Jakoby, W.B. 1974. Glutathione S-transferases: The first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 249: 7130-7139.
Howell, M.J., Board, P.G. and Boray, J.C. 1988. Glutathione S-transferases in Fasciola hepatica. The Journal of Parasitology,74: 715-718.
Iacob, O.C., El-Deeb, W. M., Pasca, S.A. and Turtoi, A.I. 2020. Uncommon co-infection due to Moniezia expansa and Moniezia benedeni in young goats from Romania: Morphological and histopathological analysis. Annals of parasitology, 66: 501-507.
Kumar, S. and Kaur, H. 2023. Molecular characterization of Moniezia denticulata (Rudolphi, 1810) and its distinction from M. expansa infecting sheep and goats raised in the north and north- western regions of India. Parasitology, 150: 831-841.
Lineweaver, H. and Burk, D. 1934. The determination of enzyme dissociation constants. Journal of the American Chemical Society, 56: 658-666.
Maldonado, G., Nava, G. and Plancarte, A. 2018. Two glutathione transferase isoforms isolated from juvenile cysts of Taenia crassiceps: Identification, purification and characterization. Journal of Helminthology, 92: 687-695.
Matoušková, P., Vokřál, I., Lamka, J. and Skálová, L. 2016. The role of xenobiotic -metabolizing enzymes in anthelmintic deactivation and resistance in helminths. Trends in Parasitology, 32: 481-491.
Mordvinov, V. and Pakharukova, M. 2022. Xenobiotic-metabolizing enzymes in trematodes. Biomedicines, 10: 3039. [https://doi.org/10.3390/biomedicines10123039].
Morello, A., Repetto, Y. and Atias, A. 1982. Characterization of glutathione S-transferase activity in Echinococcus granulosus. Comparative Biochemistry and Physiology. Part B. Comparative Biochemistry, 72: 449-452.
Mpofu, T.J., Nephawe, K.A. and Mtileni, B. 2022. Prevalence and resistance to gastrointestinal parasites in goats: A review. Veterinary World, 15: 2442.
[https://doi.org/10.14202%2Fvetworld.2022.2442-2452].
Nagarajan, G., Thirumaran, S.M.K., Pachaiyappan, K., Thirumurugan, P., Rajapandai, S., Rajendiran, A.S., Velusamy, R., Ram Vannish, M. and Kanagarajadurai, K. 2022. First report on molecular
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