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The effects of 1,8‐cineole on d‐galactosamine/lipopolysaccharide (GalN/LPS)‐induced shock model of liver injury was investigated in mice. The co‐administration of GalN (700 mg kg−1, i.p.) and LPS (5 μg kg−1, i.p.) greatly elevated serum concentrations of tumour necrosis factor‐α (TNF‐α), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8‐cineole (400 mg kg−1, p.o.) and dexamethasone (1 mg kg−1, s.c.),60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF‐α and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8‐cineole and dexamethasone treatment. The results indicate that 1,8‐cineole protects mice against GalN/LPS‐induced liver injury through the inhibition of TNF‐α production, and suggest that 1,8‐cineole may be a promising agent to combat septic‐shock‐associated pathologies.

The effects of 1,8-cineole on d-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury was investigated in mice. The co-administration of GalN (700 mg kg−1, i.p.) and LPS (5 μg kg−1, i.p.) greatly elevated serum concentrations of tumour necrosis factor-α (TNF-α), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8-cineole (400 mg kg−1, p.o.) and dexamethasone (1 mg kg−1, s.c.),60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF-α and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8-cineole and dexamethasone treatment. The results indicate that 1,8-cineole protects mice against GalN/LPS-induced liver injury through the inhibition of TNF-α production, and suggest that 1,8-cineole may be a promising agent to combat septic-shock-associated pathologies.

This study aims to evaluate the in vitroand in vivoleishmanicidal activity of lapachol, a naphthoquinone found in the seeds and heartwood of certain tropical plants, and to compare its efficacy with a reference drug, sodium stibogluconate (Pentostam®). These compounds (0.0125–4.0 mg/mL) were evaluated in vitroagainst intracellular amastigotes of Leishmania (Viannia) braziliensis(LVb), then tested in an animal model (hamster) to try to reproduce the leishmanicidal activity. In vitro, lapachol exhibited an anti‐amastigote effect, whereas in vivoit did not prevent the development of LVb‐induced lesions at an oral dose of 300 mg/kg/day for 42 days. Pentostam® demonstrated a significant anti‐amastigote effect in vitrofor LVband apparent clinical cure in vivo(60 mg/kg/day). However, it could not completely eradicate parasites from the tissues of infected animals. The observation that lapachol exerts leishmanicidal activity in vitrowithout offering significant protection against LVb‐infected lesions in hamsters suggests that lapachol in vivomight possibly inhibit the microbicidal functioning of macrophages. Alternatively, it might be transformed into an inactive metabolite(s) or neutralized, losing its leishmanicidal activity. It is also possible that an optimal and sustained plasma level of the drug could not be achieved at the dose used in this study. Copyright © 2001 John Wiley & Sons, Ltd.

This study aims to evaluate the in vitro and in vivo leishmanicidal activity of lapachol, a naphthoquinone found in the seeds and heartwood of certain tropical plants, and to compare its efficacy with a reference drug, sodium stibogluconate (Pentostam®). These compounds (0.0125–4.0 mg/mL) were evaluated in vitro against intracellular amastigotes of Leishmania (Viannia) braziliensis (LVb), then tested in an animal model (hamster) to try to reproduce the leishmanicidal activity. In vitro, lapachol exhibited an anti-amastigote effect, whereas in vivo it did not prevent the development of LVb-induced lesions at an oral dose of 300 mg/kg/day for 42 days. Pentostam® demonstrated a significant anti-amastigote effect in vitro for LVb and apparent clinical cure in vivo (60 mg/kg/day). However, it could not completely eradicate parasites from the tissues of infected animals. The observation that lapachol exerts leishmanicidal activity in vitro without offering significant protection against LVb-infected lesions in hamsters suggests that lapachol in vivo might possibly inhibit the microbicidal functioning of macrophages. Alternatively, it might be transformed into an inactive metabolite(s) or neutralized, losing its leishmanicidal activity. It is also possible that an optimal and sustained plasma level of the drug could not be achieved at the dose used in this study. Copyright © 2001 John Wiley & Sons, Ltd.