Re: Biochemical evaluation of immunotoxic effects of cadmium in rats

In a recent issue of Journal of Immunotoxicology, we read with great interest the article by Salah-Abbes et al. (2014) ‘Tunisian radish (Raphanus sativus) extract prevents cadmium-induced immunotoxic and biochemical alterations in rats’. The authors reported that, while cadmium (Cd) treatment caused some immunologic/biochemical alterations, treatment with a Tunisian radish extract helps alleviate/prevent the induced immunotoxicity. We would like to make some comments with respect to the authors’ interpretations.

In the case of acute exposure, Cd acts as a catalyst in the formation of reactive oxygen species and promotes production of inflammatory cytokines (Wolfgang & Jean-Marc, 2013). Excessive Cd exposure symptoms start within hours of an exposure and include fever, weakness, chills, etc. These symptoms may resolve after a week if there was no persistent/permanent organ injury—especially to the liver or kidneys. In the case of the kidneys, Cd especially damages the proximal tubules (Edwards and Prozialeck, 2009); if the damage is severe enough, this leads to death from renal failure. In the Salah-Abbes et al. paper, serum creatinine levels were reported within the normal range for all groups. This begs the question as to whether the Cd dosing regimen used was sufficient to induce toxic effects.

Normally, blood/urinary Cd levels provide a good index of acute excessive Cd exposure; in contrast, organ or tissue Cd concentrations are useful in predicting the potential for mortality. Additionally, any proximal renal tubular dysfunction that might arise causes decreases in blood phosphate levels (hypophosphatemia) and increases in chloride levels (hyperchloremia). In addition, there are also increases in urinary β2-microglobulin levels (Nordberg, 2010).

If there was any possible factor that caused the inflammation (such as recurring gastric gavage or bacterial contamination, etc.) and the Cd dosage used was not sufficient to produce overt toxicity, this suggests that the Tunisian radish extract prevented only onset of inflammation in the hosts in this study, not any Cd-induced immunotoxicity per se. To eliminate confusion about the source of inflammation, the authors should have presented additional data that would remove any appearance of a lack of Cd-induced immunotoxicity in their models. This could have included end-points such as rat blood or urine Cd levels, serum phosphate/chloride levels, urinary β2-microglobulin levels, and/or kidney function tests. This would have provided clearer information to the readers about the relationship between the portended Cd-induced immunotoxicity and would have then strengthened the conclusion that the radish extract in fact did ameliorate any Cd-induced immunotoxicity. For now, one should only conclude that use of the extract really only acted to mitigate any inflammation in these hosts, albeit from an undefined cause.