Chronic alcohol administration causes expression of calprotectin and RAGE altering the distribution of zinc ions in mouse testis

Abstract

Several studies reported that chronic alcohol consumption alters the intestinal mucosa barrier, and subsequent entrance of endotoxins into the bloodstream. In many tissues endotoxin exposure causes the expression of calprotectin (CP) and the receptor for advanced glycation -end products (RAGE). In this study we investigated whether chronic alcohol administration causes expression of CP and RAGE in mouse testis. The distribution of free and loosely bound Zn²⁺ (FLB-Zn²⁺) in the testicular tissues was also evaluated. Alcohol-induced testicular damage was documented by measuring testosterone blood levels and by light and electron microscope studies. Twenty mice were treated daily for three weeks with 3.0 g/kg of a 25% solution of alcohol. Ten mice were treated in the same period of time with a solution of maltose dextrins, isocaloric to alcohol. Twenty untreated mice were used as controls. Alcohol treated mice showed diffuse expression of CP and RAGE in the interstitial cells. RAGE was found also in the basal compartment of the seminiferous tubules. Depletion of FLB-Zn²⁺ was observed in the adluminal compartment of the seminiferous tubules. Expression of CP and RAGE was not found in control mice and maltose dextrin treated mice. Our results indicated novel mechanisms by which alcohol acts in testis. Indeed, CP and RAGE may cause the generation of oxidants and inflammatory mediators, with negative impact on testicular functions. Depletion of FLB-Zn²⁺ may contribute to the dysregulation of spermatogenesis.

• Alcohol
• calprotectin
• mice
• RAGE
• testis
• zinc

Declaration of interest

Grant support was received from the Ministry of University and Research, Italy. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Author contributions

Conceived and designed the experiments: FG; Performed the experiments: MCS, MAG; Analyzed the data: FG, MCS, MAG, FF, GM, RR; Contributed reagents/materials/analysis tools: FG; Wrote the manuscript: FG, MCS, MAG, FF, RR.