Comparative efficacy of piperine, curcumin and picroliv against Cd immunotoxicity in mice.
Cadmium (Cd), a well known environmental carcinogen, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic atrophy and splenomegaly. Cadmium induces apoptosis in murine lymphocytes and alters the immune functions. Thus, for the amelioration of its effect, three structurally different bioactive herbal extracts such as piperine-alkaloid, picroliv-glycosides and curcumin-polyphenols were evaluated and their efficacy compared. For ascertaining their immunomodulatory role, various biochemical indices of cell damage such as cytotoxicity, oxidative stress (ROS, GSH), apoptosis (mitochondrial membrane potential, caspase-3 activity, phosphatidylserine externalization, apoptotic DNA) along with lymphocyte phenotyping, blastogenesis and cytokine secretion were assessed in thymic and splenic cell suspensions. Of the three herbals examined, piperine displayed maximum efficacy. All the three doses of piperine (1, 10 and 50 microg/ml) increased cell viability in a dose dependent manner, whereas curcumin and picroliv were also effective, but to a lesser degree. Only the two higher doses exhibited cell viability efficacy. The median doses ie 10 microg/ml, were therefore selected, for comparison of their antioxidant, anti-apoptotic and immune function modulation. Restoration of ROS and GSH was most prominent with piperine. The anti-apoptotic potential was directly proportional to their antioxidant nature. In addition, Cd altered blastogenesis, T and B cell phenotypes and cytokine release were also mitigated best with piperine. The ameliorative potential was in order of piperine > curcumin > picroliv and former could be considered the drug of choice under immunocompromised conditions.
Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow, 226001, India.
Neelima
N
Pathak
Shashi
S
Khandelwal
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D052117:Benzodioxoles / Q000494:pharmacology*; D019256:Cadmium Chloride / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014641:Vanillic Acid / Q000494:pharmacology*
D000470:Alkaloids; D052117:Benzodioxoles; D002934:Cinnamates; D006027:Glycosides; D007376:Interleukin-2; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D017382:Reactive Oxygen Species; C057463:kutkin; D007371:Interferon-gamma; C505409:Casp3 protein, mouse; D053148:Caspase 3; D005978:Glutathione; D014641:Vanillic Acid; D003474:Curcumin; D019256:Cadmium Chloride; C008922:piperine