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Late preventive effects of quinacrine on carbon tetrachloride induced liver necrosis

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Abstract

We have previously reported that treatments stimulating phospholipid (PL) synthesis or preventing PL degradation were late preventive agents against CCl4-induced liver necrosis. Later studies by others postulated that stimulation of phospholipase A2 (PLA2) plays a role in PL degradative processes responsible for CCl4 damage. Quinacrine (QUIN) is a well known inhibitor of PLA2. In this work we report that QUIN (150 mg/kg i.p.) partially prevents CCl4-induced liver necrosis at 24 h when given 30 min before or 6 or 10 h after CCl4 (2.5 ml/kg p.o.) QUIN administration does not modify at 1 or 3 h after poisoning CCl4 levels reaching the liver, covalent binding of CCl4 reactive metabolites to proteins or lipids, CCl4-induced lipid peroxidation process, CCl4-induced decreases in body temperature, or glutathione levels in liver. QUIN concentrations in liver at times from 1 to 24 h are well over those required to inhibit PLA2 activity. Results are compatible with the hypothesis that CCl4 activation of PLA2 at late stages of poisoning plays a role in CCl4-induced liver necrosis.

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Author notes

  1. A. González Padrón

    Present address: Cátedra de Medicina Preventiva y Salud Pública. Facultad de Medicina, Universidad de La Laguna, 38071, La Laguna, Tenerife, Canarias, España

Authors and Affiliations

  1. Centra de Investigaciones Toxicológicas (CEITOX) CITEFA/CONICET, Zufriategui 4380, 1603, Villa Martelli Prov. Buenos Aires, Argentina

    A. González Padrón, E. G. D. de Toranzo & J. A. Castro

Authors
  1. A. González Padrón
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  2. E. G. D. de Toranzo
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  3. J. A. Castro
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Additional information

A. González Padrón was partially supported by a research fellowship from the Autonomic Government of the Canary Islands (Spain).

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Padrón, A.G., de Toranzo, E.G.D. & Castro, J.A. Late preventive effects of quinacrine on carbon tetrachloride induced liver necrosis. Arch Toxicol 67, 386–391 (1993). https://doi.org/10.1007/BF01977399

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  • DOI: https://doi.org/10.1007/BF01977399

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