Induction of oxidative damage in the testes and spermatozoa and hematotoxicity in rats exposed to multiple doses of ethylene glycol monoethyl ether

Abstract

<jats:p> The effects of ethylene glycol monoethyl ether (EGEE) on the antioxidant systems of the testes and epididymal spermatozoa were investigated in rats at dose levels of 0, 100, 200 and 400 mg kg<jats:sup>-1</jats:sup> body weight (bw) administered orally by gavage for 14 consecutive days. The bw gain of the EGEE-treated rats decreased significantly at 200 and 400 mg kg<jats:sup>- 1</jats:sup> bw compared with the control group. There were no significant changes in the weights of the testes, epididymis, seminal vesicles and prostate glands of the EGEE-treated rats. In the testes, while EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities, it markedly increased the malondialdehyde (MDA) level, glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities at 200 and 400 mg kg<jats:sup>-1</jats:sup> dose levels but vitamin C content remained unaffected in all the groups. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GST and LDH as well as in the levels of vitamin C and GSH but significantly increased the MDA level and SOD activity compared with the control rats. Histopathological examination showed severe degeneration of the testes, such as generalized erosion and necrosis of the germinal epithelium of the testes, but mildly affected the epididymis at 400 mg kg<jats:sup>-1</jats:sup> dose only. Data on spermatozoa analysis of EGEE-treated rats revealed significant decrease in the epididymal spermatozoa number, testicular spermatozoa number, daily spermatozoa production and spermatozoa motility but significantly increased the total spermatozoa abnormalities without affecting the spermatozoa live-dead ratio at all dose levels when compared with the control group. Results of haematological examination showed that white blood cells (WBC), platelets neutrophils and mean corpuscular haemoglobin concentration (MCHC) were significantly lower whereas lymphocytes were increased in 200 and 400 mg/kg EGEE-exposed rats than in the controls. EGEE at 100 mg/kg bw produced minor effect on haematological parameters but adversely affected testes and spermatozoa. In summary, short term administration of EGEE is hematotoxic and gonadotoxic and its effects on male reproduction could be due to the induction of oxidative stress in testes and spermatozoa. </jats:p>

Ethylene Glycol Ethers Induce Oxidative Stress in the Rat Brain

“…Like in the present study, also attenuation of antioxidant defense system and increase in lipid peroxidation appears to be the mechanism of damaging EGE action on testicular function (Adedara and Farombi 2010). Similarly, it has been shown that BE administration induced oxidative stress in the mouse liver and probably by this mechanism BE increased liver tumor (Park et al 2002).…”

“…ME and EE have predominantly gonadotoxic effect. In male rats, ME and EE disrupted testicular function by causing degeneration of spermatocytes and reduction of the number of spermatocytes and spermatids in the experimental model of intoxication (Adedara and Farombi 2010; Lamb et al 1984). In female rats, these compounds caused toxic effect mainly on ovarian luteal cells (Davis et al 1997).…”

“…However, we included it in this study, because there are no experimental data concerning its level and action in the brain, so its potential adverse effects cannot be excluded and additionally the mechanism of action of this compound in peripheral tissues is the best known, so far. For example, it has been found that EE decreased glutathione level, superoxide dismutase and catalase activity and enhanced lipid peroxidation in the rat testes (Adedara and Farombi 2010), so it potentiated oxidative stress, crucially involved also in brain cell damage. The potential adverse effect of 4-week administration of the selected EGEs on oxidative stress markers and lipid peroxidation was evaluated in the hippocampus and frontal cortex since these brain region are more susceptible to damage.…”

Ethylene glycol and propylene glycol ethers – Reproductive and developmental toxicity

“…Zaobserwowano spadek masy jąder, redukcję liczby spermatyd w jądrach oraz liczby plemników ogółem i ich odsetka o prawidłowej morfologii w najądrzach [21,22]. U szczurów narażonych per os na EGEE w dawce 400 mg/kg m.c.…”

“…Z kolei w plemnikach narażanych zwierząt wykazano spadek aktywności CAT, GST i LDH oraz stężenia witaminy C i GSH oraz wzrost aktywności SOD i stę-żenia MDA [22]. W innym badaniu u szczurów narażo-nych drogą podskórną na EGAE wykazano spadek stę-żenia związków tiolowych w jądrach, korelujący z wysokością dawek EGME, ale nie EGEE.…”