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Effect of Cannabis sativa on oxidative stress and organ damage after systemic endotoxin administration in mice

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Abstract

The effect of Cannabis sativa extract on oxidative stress and organ tissue damage during systemic inflammation was studied. For this purpose, Swiss mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg) to mimic aspects of mild systemic infection. Cannabis resin extract (5, 10, or 20 mg/kg) (expressed as Δ9-tetrahydrocannabinol) was given via subcutaneous route for 2 days prior to and at the time of endotoxin administration. Mice were euthanized 4 h after LPS injection. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (nitrite/nitrate) in the brain, liver, kidney, lung, and heart as well as brain glucose were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver homogenates. Histopathological examination of different organs was performed, and immunohistochemical techniques were used to evaluate expression levels of inducible nitric oxide synthase (iNOS) and caspase-3 in the brain and liver. The administration of only cannabis (20 mg/kg) decreased MDA, increased GSH, and decreased glucose level in the brain. No significant effects were observed for cannabis alone on MDA, GSH, or nitric oxide in other organs or on liver enzymes. The administration of LPS increased MDA and nitric oxide, while GSH decreased in different organs. Brain glucose increased by endotoxin. AST, ALT, and ALP were markedly increased in the liver tissue. In LPS-treated mice, cannabis (20 mg/kg) decreased MDA. GSH increased in the brain, kidney, and lung, nitric oxide decreased in the brain and lung while brain glucose decreased after the highest dose of cannabis. Cannabis failed to alter the level of liver enzymes. Histological damage in the brain, kidney, heart, lung, and liver due to endotoxin is increased by cannabis. Increased immunoreactivity of caspase-3 in the cytoplasm of the hepatocytes was observed after LPS and cannabis cotreatment compared with the LPS only group. Caspase-3 immunoreactivity markedly increased in degenerating neurons of the cortex following cannabis and LPS cotreatment. iNOS inmmunoreactivity increased after LPS and more intense iNOS expression was detected in hepatocytes after cannabis and LPS cotreatment. iNOS expression increased after cannabis and LPS treatment especially in the cerebral cortex. Thus, the administration of cannabis decreased tissue oxidative stress but increased organ damage after endotoxin injection in mice.

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Authors and Affiliations

  1. Department of Toxicology and Narcotics, National Research Centre, Tahrir St., , Dokki, Cairo, Egypt

    Omar M. E. Abdel-Salam, Neveen A. Salem & Marawa El-Sayed El-Shamarka

  2. Department of Pharmacology, National Research Centre, Cairo, Egypt

    Somaia A. Nada

  3. Department of Pathology, National Research Centre, Cairo, Egypt

    Enayat Omara

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  1. Omar M. E. Abdel-Salam
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  2. Somaia A. Nada
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  3. Neveen A. Salem
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Correspondence to Omar M. E. Abdel-Salam.

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Abdel-Salam, O.M.E., Nada, S.A., Salem, N.A. et al. Effect of Cannabis sativa on oxidative stress and organ damage after systemic endotoxin administration in mice. Comp Clin Pathol 23, 1069–1085 (2014). https://doi.org/10.1007/s00580-013-1745-1

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