Determination of lipid peroxidation and cytotoxicity in calcium, magnesium, titanium and hectorite (SHCa-1) suspensions.

This paper reports data on the relative ability of CaO, CaCl2, MgO, MgCl2, TiO2, and hectorite (SHCa-1) to induce oxidative stress (as determined by lipid peroxidation, LP) in biological matrices. The effectiveness of structural (oxide form) versus soluble Ca and Mg to induce LP is compared. An assessment on cytotoxicity as affected by soluble and structural Ca, Mg, TiO2 and SHCa-1 is also addressed. LP was screened and monitored using the Thiobarbituric Acid Reactive Substances (TBARS). The extent of TBARS production was found to vary with the type and initial concentration of the soluble or structural cation, Ca or Mg respectively. Obtained results showed higher magnitude values for the latter set of experiments. In the presence of TiO2 no significant TBARS production was detected pointing out a negligible effect of TiO2 on LP. At solid concentrations ca. 100 ppm, CaO appears to be more effective than SHCa-1 to induce LP. By contrast at ca. 25 ppm, MgO appears to be more effective than the clay mineral. The SHCa-1 LP-inducing activity has been proven to closely relate to structural Ca. The prevalence of mechanisms that may induce LP but not cytotoxicity (as determined by cell growth inhibition) was also addressed. Results on cell growth inhibition as affected by soluble and structural Ca, Mg, TiO2 and hectorite provide evidence to support that structural Ca or Mg brings about significantly higher variations than soluble Ca.

Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage due to direct DNA-metal interaction?

Even though the toxic effects of lead and cadmium compounds have been studied over many years, inconsistent results have been obtained about their mutagenic, clastogenic and carcinogenic properties. However, these metals are considered to be potential human carcinogens. The mechanism of metal-induced carcinogenesis is still unknown, but one possible pathway may involve the interaction of metals with DNA, either directly or indirectly. In this work we explore the capacity of lead, cadmium or a mixture of both metals to interact with acellular DNA, by employing a variant of the comet assay. Our results, using low non-cytotoxic metal concentrations (0.01, 0.1 and 1.0 microM) with the standard protocol for the acellular assay, showed an induction of DNA damage in cells of all organs studied; however, basal DNA damage was different in each organ. To confirm that we were working with pure DNA, proteinase K was added to the lysis solution. With this enriched-lysis solution we found a negative response in the induction of DNA damage in cells derived from the liver, kidney and lung of CD-1 male mice. To support the results obtained by the enriched-acellular assay, we studied the capacity of lead and cadmium (0.1 microM) to induce breaks in pooled genomic DNA in cells of the same organs, with negative results. Consistent with these findings, these metals do not induce DNA breaks in the plasmid pUSE amp+. On the whole, we did not detect direct induction of DNA strand breaks by lead acetate, cadmium chloride or a mixture of both metals, all at low non-cytotoxic concentrations. However, we found an induction of lipid peroxidation and an increase in free radical levels in the different organs of CD-1 male mice after inhalation of lead acetate (0.0068 microg/cc) or cadmium chloride (0.08 microg/cc) for 1 h, suggesting the induction of genotoxicity and carcinogenicity by indirect interactions, such as oxidative stress.

Reduction of streptomycin-induced acute and chronic toxicities.

The acute and chronic toxicities of streptomycin sulfate (SS) and of the streptomycin hydrochloride-calcium chloride complex (SCC) were compared. The LD50 determined in mice was significantly higher for SCC than for SS. Chronic toxicity was evaluated by recording the nystagmus induced by damped torsion pendulum in rabbits. SS and SCC treatments (200 mg/kg intramuscularly of absolute streptomycin base) decreased the duration, the maximal frequency, and the total number of beats of nystagmus. However, SCC-induced changes were significantly lower than SS-induced ones. The extent of the lesion in the crista ampullaris was evaluated by light and electron microscopy and was correlated with the electrophysiological findings. Because the authors also demonstrated that there are no differences in the antibacterial effects of these salts, SCC may have a place in long-term streptomycin treatment.