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 Zn 2+ ) 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-Zn 2+ 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-Zn 2+ may contribute to the dysregulation of spermatogenesis.Abbreviations: CP: calprotectin; FLB-Zn 2+ : free and loosely bound Zn

Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury

“…Acetaldehyde can form AA-DNA adducts in the brain and in peripheral blood leukocytes of people with AUD since ethanol, acetaldehyde, and lipid aldehydes such as MDA and 4-HNE can inhibit DNA repair enzymes 53 . The dual [251][252][253][254][255] Erythrocytes AA adducts ↑ correlated with FASD 257,258 Testis RAGE overexpression ↑ oxidative stress and inflammation↑ testis dysfunction and degeneration 253,[259][260][261] ↑ increase/activate, ↓ decrease/inactivate. mechanisms of simultaneously elevated AA-DNA adducts and suppressed DNA repair systems following alcohol intake may contribute to genetic instability and DNA mutations, promoting neurological pathologies 192,197,198 .…”

“…Alcohol intake can induce RAGE overexpression in the testis, whereby RAGE is localized in the interstitial cells and the basal compartment of the seminiferous tubules. Prolonged ethanol exposure stimulates RAGE activation to produce oxidative stress and inflammatory mediators, leading to testicular dysfunction and degeneration 259 . CYP2E1 and ALDH2 are also expressed in the testis 253,260,261 .…”

Virgin coconut oil protected the diameter and the epithelium thickness of seminiferous tubules of mice (Mus musculus) from oral ethanol induction

“…It was proven that the consumption of ethanol excessively caused a decrease in the diameter, degeneration of sperm cells and germ cells, and the thinning of seminiferous tubules. It was indicated that alcohol damage happens due to the testicular interstitial cells and seminiferous tubules, especially the peritubular wall of the latter (Giannessi et al, 2015). It was reported that excessive alcohol intake resulted in testicular atrophy and gonadal failure.…”