Abstract
Background: Ricin toxin is considered one of the most potent plant-derived toxins. It induces rapid and irreversible toxic effects through many mechanisms with special concern to inhibition of protein synthesis and oxidative stress resulting in cell death. Moreover, ricin could be used as a terrorist weapon which indicates the importance of finding a specific treatment. Alpha lipoic acid (ALA) possesses almost all characters of an ideal antioxidant; thereby it is suggested to be used against ricin toxicity. Aim of the work: The current study aimed at investigating the acute toxic effects of ricin on the kidneys of adult male albino rats and to appraise the possible protective effect of ALA in altering ricin-induced nephrotoxicity. Material & Methods: the present study was carried out on 60 adult male albino rats; they were divided into four groups. Group I: ten rats were intraperitoneally injected by 0.9% saline. Group II:tenrats were intraperitoneally injected by 100 mg/kg ALA. Group III: twentyrats were subcutaneously injected once with 25 µg/kg body weight of ricin solution. Group IV: twenty rats were injected by 100 mg/kg ALA, 15 minutes prior to single injection of 25 μg/kg body weight of ricin solution, and then reinjected with the same dose of ALA immediately after ricin injection. Survival time, renal function tests, renal malondialdehyde (MDA), renal superoxide dismutase (SOD) and catalase enzyme activities were recorded. Kidney samples were used for electron microscopic examination. Results: Ricin induced nephrotoxicity with significant increase of renal function tests, renal MDA and catalase activity with significant decrease of SOD. Also, the kidney samples of ricin-treated animals revealed focal ultrastructural changes in renal corpuscles, proximal and distal convoluted tubules. On the other hand, most of ricin-induced injuries were much improved after administration of ALA together with ricin. Conclusion: Ricin produces oxidative nephrotoxic effects that markedly improved by the effective antioxidant properties of alpha lipoic acid.
Highlights
Ricin toxin (RT) is considered one of the most potent and lethal naturally-occurring substances that ever known; in humans, the median lethal dose of ricin (LD50) after injection or inhalation is about 22 μg/kg of body weight, the estimated lethal oral dose is 1 mg/kg
The severity of ricin toxicity depends on its route of administration with most potent toxicity through inhalation and least toxicity through oral administration
The possible use of ricin as a terrorist weapon indicates the importance of finding specific treatment
Summary
Ricin toxin (RT) is considered one of the most potent and lethal naturally-occurring substances that ever known; in humans, the median lethal dose of ricin (LD50) after injection or inhalation is about 22 μg/kg of body weight, the estimated lethal oral dose is 1 mg/kg. Ricin is known to have rapid and irreversible toxic effects through different possible mechanisms including protein synthesis inhibition, magnesium and calcium imbalances, apoptosis pathways, cytokine release, acute phase reactions, and oxidative stress. Alpha lipoic acid (ALA) possesses almost all characters of an ideal antioxidant; thereby it is suggested to be used against ricin toxicity. Aim of the work: The current study aimed at investigating the acute toxic effects of ricin on the kidneys of adult male albino rats and to appraise the possible protective effect of ALA in altering ricin-induced nephrotoxicity. Group III: twenty rats were subcutaneously injected once with 25 μg/kg body weight of ricin solution. Results: Ricin induced nephrotoxicity with significant increase of renal function tests, renal MDA and catalase activity with significant decrease of SOD. Conclusion: Ricin produces oxidative nephrotoxic effects that markedly improved by the effective antioxidant properties of alpha lipoic acid
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