The Hepatic Effect of Sub-chronic Chronic Cadmium Exposure.

Introduction and Objectives

MAFLD is an umbrella disease characterized by lipids storage. Epidemiological studies found that cadmium (Cd) exposure is related to the development of MAFLD. We're interested in evaluating the effect of Cd exposure on lipid accumulation in the liver.

Materials and Patients

Eight-week-old CD-1 mice were exposed to Cd (10mg/L) for one and three months, sub-chronic and chronic models, respectively; they were fed with a Chow diet, recording the weight of the animals periodically. Euthanasia was performed, and the liver was macroscopically inspected. Liver damage enzymes were assayed in serum. Liver sections were stained with H&E for morphometric analysis, Sirius red for fibrosis, and Red Oil O (ORO) for lipids. By biochemical studies, we determined the triglycerides and cholesterol content in the liver. The protein content of MAPKs was evaluated by western blot.

Results

Cd consumption in both models did not affect the weight of the mice. However, it promoted intestinal inflammation during one month of exposure. Liver/body weight ratio was obtained, despite which Cd was not found to promote hepatomegaly at one and three months of exposure. By H&E, we found that sub-chronic exposure to Cd favored hepatocyte proliferation, and chronic exposure triggered death after cell proliferation; despite this, liver damage enzymes did not increase in serum following sub-chronic and chronic exposure. Subsequently, we evaluated fibrosis in chronic treatment without finding that Cd promotes its accumulation of collagen in the liver. Likewise, we analyzed hepatic triglyceride and cholesterol accumulation without finding that Cd causes lipid accumulation after sub-chronic and chronic exposure. Finally, we evaluated the activation of MAPKs in our model. We found that Cd favors the activation of p38 and the repression of JNK in chronic exposure, suggesting a damage-repair mechanism.

Conclusions

Sub-chronic and chronic exposure to Cd (10 mg/L) does not affect physiological parameters; however, activation of p38 is observed, suggesting a liver damage/repair mechanism and possible repression of JNK, which could prevent lipid accumulation.