Toxicity of Atractyloside in Precision-Cut Rat and Porcine Renal and Hepatic Tissue Slices

Obatomi, David K.; Brant, Stephen; Anthonypillai, V.; Bach, Peter H.

doi:10.1006/taap.1997.8316

Cited by 22 publications

(21 citation statements)

References 29 publications

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“…Furthermore, tissue culture studies indicate that atractylosides exert both hepatotoxicity and nephrotoxicity through selective toxicity at the liver and the kidneys, probably due to speci®c uptake mechanisms. In both organ tissues evidence for marked oxidative stress, expressed as glutathione depletion and increase of lipid peroxidation, were observed 81 . Another plant species containing atractylosides is Callilepsis laureola which has been associated with several cases of fulminant hepatitis and renal tubular necrosis among Zulus in South Africa 82 .…”

Section: Atractylis Gummifera and Callilepsis Laureolamentioning

confidence: 99%

Hepatotoxicity of botanicals

Stickel

Egerer

Seitz

2000

Public Health Nutr.

133

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Objective: Hepatic impairment resulting from the use of conventional drugs is widely acknowledged, but there is less awareness of the potential hepatotoxicity of herbal preparations and other botanicals, many of which are believed to be harmless and are commonly used for self-medication without supervision. The aim of this paper is to examine the evidence for hepatotoxicity of botanicals and draw conclusions regarding their pathology, safety and applications. Design: Current literature on the hepatotoxicity of herbal drugs and other botanicals is reviewed. The aetiology, clinical picture and treatment of mushroom (Amanita) poisoning are described.

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Section: Atractylis Gummifera and Callilepsis Laureolamentioning

confidence: 99%

Hepatotoxicity of botanicals

Stickel

Egerer

Seitz

2000

Public Health Nutr.

133

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“…The main toxic component in cocklebur is regarded as atractyloside (Cole et al, 1980), which also exists in Callilepsis laureola (Mokhobo, 1976) and Atractylis gummifera (Larrey, 1997). The toxicity of atractyloside is reportedly caused by the inhibition of energetic pathway (Allmann et al, 1967) and induction of oxidative stress as lipid peroxidation and GSH depletion in liver slices (Obatomi et al, 1998). In contrast to the clear mechanism of atractyloside, studies on cocklebur hepatotoxicity are quite absent and thus further investigation is still needed.…”

Section: Introductionmentioning

confidence: 95%

Effects of glycyrrhizic acid on cocklebur‐induced hepatotoxicity in rat and human hepatocytes

Yin

et al. 2007

Phytotherapy Research

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Herbal medicines are gradually being accepted for their low toxicity and high efficacy, but their hepatotoxicity still needs to be recognized. For the multiple compounds in herbs, hepatocytes in vitro would be a useful tool for the evaluation of herbal hepatotoxicity. This study aimed at cocklebur/atractyloside-induced hepatotoxicity and the protective effects of glycyrrhizic acid (GA) against this toxicity using rat and human hepatocytes in monolayer culture. After a 48 h treatment, cocklebur as well as atractyloside induced concentration-dependent hepatotoxicity according to obvious decreases of cell viability, intracellular glutathione (GSH) content and albumin secretion in rat hepatocytes. Compared with rat hepatocytes, human hepatocytes seemed to be less sensitive to cocklebur-induced hepatotoxicity, indicative of species differences between humans and rats. Furthermore, as expected, GA showed significant protective effects on cocklebur hepatotoxicity in both human and rat hepatocytes. Overall, these results suggested that hepatocytes in vitro, particularly human hepatocytes, could be a useful tool for herbal hepatotoxicity screening in vitro.

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“…Atractyloside was dissolved in DMEM/F12 medium to give a ®nal concentration of 2.0 mM, which was based on results of previous experiments (Obatomi et al 1998c). ADP was similarly dissolved in DMEM/F12 medium to give a ®nal concentration of 5.0 mM.…”

Section: Preparation Of Atractyloside and Tested Compoundsmentioning

confidence: 99%

“…Trichloroacetic acetic acid (TCA, 0.5 ml, 0.39 M) was used to precipitate the protein in the slices and the level of GSH measured as soluble thiols (Obatomi et al 1998c). Samples were then centrifuged at 3000 rpm for 10 min.…”

Section: Assessment Of Reduced Glutathione (Gsh)mentioning

confidence: 99%

“…It is well established that this compound produces an acute, mainly proximal tubule, functional impairment within hours of administration to animals (Carpenedo et al 1974;Luciani et al 1978) and also exhibits cell speci®c cytotoxicity in vitro, which was con®ned to the proximal tubule (Obatomi and Bach morphology, destruction of the tubulin network within the cytoplasm and inhibition of cell division (Stewart and Steenkamp 2000). Atractyloside is also known to induce mild oxidative damage and inhibit oxidative phosphorylation, which prevents the synthesis of ATP and leads to failure of gluconeogenesis and ultimately cell death (Obatomi et al 1998c). Consequently it is likely that more than one molecular mechanism is involved in atractyloside toxicity and that the mechanisms may vary with the cell type and tissue.…”

Section: Introductionmentioning

confidence: 99%

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Adenine nucleotide and calpain inhibitor I protect against atractyloside-induced toxicity in rat renal cortical slices in vitro

Obatomi

Blackburn

Bach³

2001

Archives of Toxicology

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Atractyloside is a compound with a documented nephrotoxicity. It induces renal tubular necrosis at high doses and apoptosis at lower doses. This study investigates the potential protective effect of some chemical agents against atractyloside-induced nephrotoxicity in vitro using the precision-cut rat renal cortical slices obtained from kidneys of Wistar rats. For co-incubation experiments, slices were incubated for 3 h at 37 degrees C on a rocker platform with various chemical agents: ADP (5 mM), calpain inhibitor I (CPI, 1 mM), stevioside (STV, 2.5 mM) or probenecid (PRB, 2.5 mM) in the presence or absence of atractyloside (2 mM). For pre-incubation experiments, slices were incubated with the same chemical agents for 1 h before exposure to atractyloside. The nephrotoxic effects of atractyloside (2 mM) alone were manifested in several ways: by a marked increase in lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) leakage, significant inhibition of p-aminohippurate (PAH) accumulation, marked depletion of intracellular ATP and reduced glutathione (GSH), and a significant reduction in pyruvate-stimulated gluconeogenesis. Co-incubation of slices with ADP or CPI and atractyloside completely blocked atractyloside-induced increase in LDH leakage, but not ALP leakage. Atractyloside-induced depletion of ATP and reduced gluconeogenesis was prevented by co-incubation with ADP or CPI. Furthermore, co-incubation of slices with STV and atractyloside, but not PRB, completely abolished atractyloside-induced depletion of ATP and decreased gluconeogenesis in the slices. Pre-incubation of slices with either ADP or CPI protected against atractyloside-induced increase in LDH leakage, reduced ATP and decreased gluconeogenesis. PAH uptake in the slices was inhibited by atractyloside and PRB in a time-dependent manner. While ADP and CPI were found to exert complete protection against atractyloside-induced toxicity irrespective of treatment schedule, STV is effective only under certain conditions, and PRB offer no protection at all. The results of this study demonstrate the usefulness of renal cortical slices as toxicology tool for evaluating and screening compounds for their potential protective effects, and are supportive of a role of adeninine nucleotide (ADP) and protease inhibitor (CPI) in protecting against atractyloside-induced cell injury.

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Toxicity of Atractyloside in Precision-Cut Rat and Porcine Renal and Hepatic Tissue Slices

Cited by 22 publications

References 29 publications

Hepatotoxicity of botanicals

Hepatotoxicity of botanicals

Effects of glycyrrhizic acid on cocklebur‐induced hepatotoxicity in rat and human hepatocytes

Adenine nucleotide and calpain inhibitor I protect against atractyloside-induced toxicity in rat renal cortical slices in vitro

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