Other Mechanisms

Reactive nitrogen species: Nitric oxide is an inflammatory mediator produced by the inducible form of nitric oxide synthase (iNOS). It is converted into a variety of reactive nitrogen species, which eventually yield nitrite as a stable product that can be measured in serum and tissues. There are indications that reactive nitrogen species are involved in the toxicity of a variety of drugs, including the renal tox-icity of gentamicin and cisplatin and the nephrotoxicity of cyclosporine. When S. fusiformis was given orally to mice 2 days before and 8 days concomitantly with gentamicin a dose-dependent inhibition of the gentamicin-induced increase in serum nitrite concentrations was observed.19 Similar results were obtained in animals that were treated orally with S. fusiformis for 2 days before and 3 days during administration of cisplatin.18 In this study, Spirulina was somewhat less effective in decreasing serum nitrite concentrations, possibly because it was given for a shorter duration than in the gentamicin study. Other investigators showed that Spirulina was able to inhibit hepatic iNOS activity,22 and this ability may account for the observed reduction in serum nitrite levels in the above studies.

Prevention of apoptosis: As discussed earlier, Spirulina significantly attenuated DOX-induced cardiomyopathy.9 In vitro results obtained by the same group of researchers suggest that one of the mechanisms involved in the cardioprotective effect of Spirulina is the prevention of cardiomyocyte apoptosis, a tightly regulated cellular suicide program.10 Both Spirulina and phycocyanin were able to markedly inhibit apoptosis. Oxidative stress is well known to induce this form of cell death, and the radical scavenging and antioxidant activities of Spirulina and phycocyanin may have contributed to the inhibition of DOX-induced apoptosis in cardiomyocytes.

In addition, however, both Spirulina and phycocyanin reversed the DOX-induced increase in the activity of caspase-3. Caspases are central mediators of apoptosis, and caspase-3 is indispensable for several steps within the apoptotic process. Furthermore, phycocyanin was able to significantly inhibit the drug-induced increase in the expression of the proapoptotic Bax protein. It also induced the expression of Bcl-2, an antiapoptotic molecule. No results were reported for Spirulina.

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