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Curcumin attenuates indomethacin-induced oxidative stress and mitochondrial dysfunction

  • Molecular Toxicology
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Abstract

Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of indomethacin-induced enteropathy. We evaluated the potential of curcumin, a known cytoprotectant, as an agent to protect against such effects. Rats were pretreated with curcumin (40 mg/kg by intra-peritoneal injection) before administration of indomethacin (20 mg/kg by gavage). One hour later, the small intestine was isolated and used for assessment of parameters of oxidative stress. Mitochondria, brush border membranes (BBM) and surfactant-like particles (SLP) were also isolated from the tissue. Mitochondria were used for assessment of functional integrity, estimation of products of lipid peroxidation and lipid content. BBM were used for estimation of products of lipid peroxidation and lipid content, while the SLP were used for measurement of lipid content. The results showed that oxidative stress and mitochondrial dysfunction occurred in the small intestine of indomethacin-treated rats. Pre-treatment with curcumin was found to ameliorate these drug-induced changes. Significant changes were seen in some of the lipids in the mitochondria, BBM and SLP in response to indomethacin. However, curcumin did not have any significant effect on these drug-induced changes. We conclude that curcumin, by attenuating oxidative stress and mitochondrial dysfunction, holds promise as an agent that can potentially reduce NSAID-induced adverse effects in the small intestine.

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Abbreviations

BBM:

Brush border membranes

MDA:

Malondialdehyde

MTT:

3-[4,5-Dimethylthiazol-2-yll]-2,5-diphenyltetrazolium bromide

NSAIDs:

Non-steroidal anti-inflammatory drugs

RCR:

Respiratory control ratio

SLP:

Surfactant-like particle

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Acknowledgments

The authors would like to acknowledge the Council for Scientific and Industrial Research (CSIR), New Delhi, India (grant no. 37/1182/04 EMRII) for financial assistance for the study. Both Jayasree Basivireddy and Nageswaran Sivalingam were Senior Research Fellows funded by the CSIR.

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Authors and Affiliations

  1. Department of Biochemistry, Christian Medical College, Vellore, 632002, Tamil Nadu, India

    Nageswaran Sivalingam & Molly Jacob

  2. Department of Gastrointestinal Sciences, The Wellcome Trust Research Laboratory, Christian Medical College and Hospital, Vellore, 632004, Tamil Nadu, India

    Jayasree Basivireddy & Kunissery A. Balasubramanian

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  1. Nageswaran Sivalingam
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  3. Kunissery A. Balasubramanian
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Correspondence to Molly Jacob.

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Sivalingam, N., Basivireddy, J., Balasubramanian, K.A. et al. Curcumin attenuates indomethacin-induced oxidative stress and mitochondrial dysfunction. Arch Toxicol 82, 471–481 (2008). https://doi.org/10.1007/s00204-007-0263-9

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