After exposure to 1 ng/mL PCDD/Fs and 10 ng/mL DL-PCBs, there was no significant change in the body weight and liver weight of female and male rats, or in the hepatosomatic index of female rats, whereas the hepatosomatic index of male rats was increased obviously, implying that the exposure to PCDD/Fs and DL-PCBs probably caused damage to the liver. After intervention of curcumin, the hepatosomatic index of the rats was decreased, indicating that the liver injury may have recovered. The protective effect of curcumin against liver injury has also been discovered in research on liver injury induced by carbon tetrachloride, ischemia–reperfusion, and alcohol. One study found that, as for exposure to TeCDD congeners, TeCDD toxicity is variable in different species, different strains within the same species, and different sexes within the same strain. Moreover, female Long–Evans rats are more sensitive to the acute lethality of TeCDD than males are, while male mice and guinea pigs are more sensitive to TeCDD toxicity than females are.[12, 13] In the present study, the male rats had higher sensitivity to the hepatotoxicity of POPs with a diphenyl ring, inconsistent with reports in the literature. The possible reason is that the SD rats were used as the laboratory murine strains and exposed to a low-concentration mixture (10 kinds of PCDD/Fs and 12 kinds of PCBs) for 28 days, which is different from previous studies, so the sex-dependent toxic effect may have been different.
The intervention of curcumin could have markedly decreased the bioavailability of WHO-PCDD/F-TEQ, WHO-DL-PCB-TEQ and total TEQ in the liver of male rats, but it was merely able to reduce the bioavailability of WHO-PCDD/F-TEQ in the liver of female rats, indicating that curcumin can attenuate the bioavailability of DL-POPs. These results suggest that the decrease in the bioavailability of DL-POPs may be a detoxification mechanism of curcumin in these indicators.
Following the intervention of curcumin, the bioavailability of tetra- and penta-chlorinated PCDDs (including 2,3,7,8-TeCDD and 1,2,3,7,8-PeCDD, with a TEF of 1) and tetra- and penta-chlorinated PCDFs (including 2,3,7,8-TeCDF and 1,2,3,7,8-PeCDF, with a TEF of 0.1 and 0.03, respectively) was reduced markedly in male rats, and the impact on the bioavailability of WHO-PCDD/F-TEQ calculated based on wet weight was greater. No significant change in the bioavailability of hexa-chlorinated PCDD/F and OCDF (8Cl) was observed. The bioavailability of hepta-chlorinated PCDD/F (TEF = 0.01) and OCDD (TEF = 0.0003) was increased, which had a small influence on the bioavailability of WHO-PCDD/F-TEQ. In addition to no obvious changes in the bioavailability of tetra- to hexa-chlorinated PCDFs, variations in bioavailability of the remaining PCDD/Fs in female rats were similar to those in male rats. The bioavailability of WHO-PCDD/F-TEQ was decreased in female and male rats, illustrating that curcumin is capable of decreasing the bioavailability of PCDD/Fs. The chemical structure (diphenyl structure) of curcumin resembles that of PCDD/Fs and may competitively repress the absorption of PCDD/Fs in small intestinal epithelial cells. Nevertheless, the specific mechanism of curcumin in lowering the bioavailability of PCDD/Fs remains unclear and needs to be verified. A previous study revealed that curcumin can inhibit the absorption of other chemical substances such as cholesterol in the intestinal tract.
In female rats receiving intervention with curcumin, only the bioavailability of PCB169 (TEF = 0.03) declined prominently, while the bioavailability of PCB81 and PCB123 was increased clearly, and no obvious changes in the bioavailability of the other PCBs was observed. However, these changes were not significant, so the overall bioavailability of WHO-DL-PCB-TEQ calculated based on wet weight showed no obvious variation. Moreover, in the liver of male rats, the bioavailability of PCB156 (TEF = 0.00003), PCB167 (TEF = 0.00003) and PCB169 showed significant decreases, and the bioavailability of PCB126 (TEF = 0.1) dropped slightly but not significantly. For other PCBs, changes in bioavailability were not apparent, and the bioavailability of WHO-DL-PCB-TEQ calculated based on wet weight was reduced, implying that there is a significant sex difference in the intervention effect of curcumin on the bioavailability of PCBs. As a category of typical endocrine-disrupting chemicals with estrogen and antiandrogen effects, PCBs can affect the function of the hypothalamus–pituitary (HP) axis and hinder the synthesis, metabolism and action of hormones. The decreased bioavailability of PCBs in males may be related to the functional change of the HP axis, which needs to be confirmed. Bioavailability of PCDD/Fs and PCBs had independent change patterns along with the increase in number of chlorine atoms in the molecular structure. Specifically, the bioavailability of tetra- to hexa-chlorinated PCDD/Fs was elevated gradually, that of hepta- and octa-chlorinated PCDD/Fs was lowered, and that of PCBs displayed no obvious change patterns. Nevertheless, the change patterns of those indicators were not altered by the intervention of curcumin.
Distribution of PCDD/Fs in tissues primarily depends on the structure, chlorination level, dose range, absorption, metabolism and transport in blood of homologs. Kim et al. applied the quantitative structure–property relationship method to predict the physicochemical properties of PCDD homologs, and revealed that as the number of substituted chlorine atoms was increased, the water solubility of PCDDs was gradually weakened, while the octanol–water partition coefficient (KOW, logKOW is a substitute index of lipid–water partition coefficient) was raised gradually, indicating that highly chlorinated PCDDs are preferentially absorbed in the small intestine, and thus their bioavailability is relatively high in the liver. However, the preferential absorption law of more chlorine atoms is limited over a certain range because the organic pollutants with too high logKOW and too low water solubility are not conducive to absorption by cells. Moreover, it has been found that the bioavailability of OCDD and OCDF (8Cl) in the liver and kidney fat of sheep is low. Budinsky et al. reported that the bioavailability of 2,3,7,8-TeCDF and 1,2,3,7,8-PeCDF is low, and that of 1,2,3,6,7,8-HxCDF is high in the rat liver, which is in line with the results of our study, but the bioavailability of 2,3,4,7,8-PeCDF was higher. Why is the bioavailability of 1,2,3,7,8-PeCDF and 2,3,4,7,8-PeCDF, both of which are pentachlorides, different? Kim et al. also demonstrated that PCDD homologs have the same number of chlorine atoms, but the substituted positions and KOW are different. It may be that furans have similar conditions. Researchers have discovered that the level of PCDD/Fs in deer tissues is almost twice that in wild boar tissues, and the bioaccumulative coefficients (the ratio of the concentration in the muscle to the concentration in the environmental samples) in both deer and wild boar decrease with the increase in chlorine atom number in PCDD/F molecules. Such an accumulation mode of PCDD/F homologs differs from that in the present study, suggesting that there are differences in the absorption modes of PCDD/Fs between various species and between low-level exposure in the field and high-level exposure in the laboratory.
The pattern where there is no obvious change rule in the bioavailability of PCBs has also been reported in studies on wild boar and deer. However, Zhang et al. utilized loaches in rice paddy fields to investigate the bioaccumulation of organochlorine pesticides and PCBs, and discovered that the bioaccumulation was affected by environmental factors (temperature, soil, etc.), biological factors (species) and chemical factors. In the majority of bioaccumulation models, the bioaccumulation factors of organochlorine compounds are often associated with KOW. When logKOW is increased from 6.0 to ~ 7.0, the bioaccumulative coefficient of PCBs increases, but the bioaccumulation factor declines conversely as logKOW increases continuously. Moreover, it has been observed that PCB156 and PCB157 have the highest accumulative coefficients. It can be seen that the bioavailability may vary from species to species. There were some limitations to this study. For example, the number of animals in each group was small, and the individual differences were large, so it is difficult to obtain significant differences. Besides, the bioavailability of PCDD/Fs and PCBs was only examined in the liver, and their content in other tissues and excretion in urine and feces were not tested. Additionally, not all PCDD/Fs and PCBs were investigated; thus, the effects of curcumin on the bioavailability of PCDD/Fs and PCBs could not be assessed comprehensively. The above limitations need to be improved by subsequent studies.