Effect of caffeine and ethanol intake on di (2-ethylhexyl) phthalate (DEHP)-induced testicular atrophy
Authors: Shigeru Suna  , Fumihiko Jitsunari  
Published: April 2023

Background: Di(2-ethylhexyl) phthalate (DEHP) is the most widely used polyvinyl chloride (PVC) plasticizer. Therefore, DEHP pollution is spreading all over the world. In recent years, it has attracted attention as an endocrine disrupting chemical. In animal experiments using rodents, testicular toxicity has been confirmed by feeding diets containing DEHP. Mono(2-ethylhexyl) phthalate (MEHP), a potent oxidative stressor, is thought to be directly involved in testicular toxicity. On the other hand, caffeine and ethanol, which are hydroxyl radical scavengers, are taken in relatively large amounts from food and drink on a daily basis. Although the reproductive toxicity of DEHP in humans remains unclear, it is important to clarify the relationship between DEHP toxicity and caffeine and ethanol intake through animal experiments. Method: To investigate the effects of caffeine and ethanol intake on DEHP-induced testicular atrophy, rats were fed a 1 w/w % DEHP diet and caffeinated water (0.05 w/w %) or ethanol water (2.5 or 5 v / v %) or ethanol plus caffeine water for one week. Result: By administering 1 w/w % DEHP-containing diet for one week, significant testicular weight decrease noted in all cases, and testicular MEHP concentration in the control group and DEHP–only administered group showed a strong negative correlation with the relative testicular weight (as a percentage of body weight). This indicates that there is a close relationship between the tissue MEHP concentration and testicular atrophy in the target organ, the testis. In addition, it was found that the increase in Fe, Cu, and Ca concentrations in the testis was closely related to the decrease in relative testicular weight. Furthermore, multiple linear regression analysis suggested that the MEHP concentration in the testis was significantly related to the increase in the Cu concentration in the testis. This suggests that MEHP oxidative stress may induce the SOD enzyme. Also, caffeine administration was found to slightly but significantly improve Zn levels. On the other hand, caffeine treatment significantly inhibited the decrease in testicular weight. Also, the testicular weight decrease in the ethanol and caffeine administration groups was less than that in the DEHP-only administered group. These findings suggest that ethanol and caffeine may inhibit DEHP testicular atrophy. In addition, in this administration experiment, the relative testicular weight vs. testicular MEHP plot in the ethanol and caffeine administered groups was clearly distributed above the regression line obtained from the relationship between the relative testicular weight and testicular MEHP concentration in the control and DEHP-only administered groups. From this, it was suggested that administration of DEHP in combination with ethanol or caffeine reduced DEHP testicular toxicity. Furthermore, multiple linear regression analysis suggested that combined use of ethanol and caffeine had a combined effect of reducing testicular atrophy. Conclusion: Daily use levels of caffeine and ethanol were found to reduce DEHP-induced testicular toxicity in rats