Effects of Zn deficiency, antioxidants, and low-dose radiation on diabetic oxidative damage and cell death in the testis

Abstract

Infertility is one of the common complications in diabetic men and mainly due to the loss of germ cells by apoptotic cell death. Although several mechanisms have been proposed to explain the induction of testicular cell death by diabetes, diabetic induction of testicular oxidative stress and damage may be the predominant mechanism responsible for the testicular cell death in diabetes. To explore whether factors that either increase or decrease the testicular oxidative stress and damage will enhance or prevent diabetes-induced testicular cell death, the effect of zinc (Zn) deficiency on diabetes-induced cell death has been examined since Zn was found to play an important role in the protection of testis from oxidative stress and damage. Zn deficiency, induced by its chelator N,N,N,N-Tetrakis(2-pyridylmethyl)-1,2-ethylenediamine, was found to exacerbate diabetes-induced testicular oxidative damage and cell death. In contrast, treatment of diabetic rats with antioxidant N-acetylcysteine or low-dose radiation that can up-regulate endogenous antioxidants significantly attenuated diabetes-induced testicular cell death. These results suggest that diabetes-induced testicular cell death that may eventually cause men's infertility is predominantly mediated by the oxidative stress and damage. To prevent or delay diabetes-caused infertility, diabetic patients should avoid Zn deficiency, and might consider antioxidant supplementation.

Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function

“…Studies with animal models from our own laboratory have clearly indicated that male germ cell death in T1DM mice or rats was mediated predominantly by the mitochondrial cell death pathway (45,50) and also the ER stress cell death pathway (47). In an animal study where mice were exposed to cadmium, testicular cell death was increased significantly via the ER stress pathway.…”

Repetitive exposure to low-dose X-irradiation attenuates testicular apoptosis in type 2 diabetic rats, likely via Akt-mediated Nrf2 activation

“…T2DM features two physiological defects: peripheral tissue's resistance to the action of insulin and a deficiency in insulin secretion at late stage (Andrikopoulos et al, 2008; Taylor, 1999). Accordingly an insulin-defective stage of T2DM (IDS-T2DM) rat model was created by high-fat diet (HFD) feeding containing 60 kcal% fat for 2 months to induce insulin resistance, followed by a small dose (25 mg/kg of body weight) of STZ (Sigma Aldrich, St. Louis, MO, USA) to cause mild deficiency of insulin with hyperglycemia, as described in our previous (Zhao et al, 2013) and other studies (Kusakabe et al, 2009; Luo et al, 1998; Mu et al, 2006). Control rats were fed with the control diet (CD), containing 10 kcal% fat.…”

Oxidative effects of extremely low frequency magnetic field and radio frequency radiation on testes tissues of diabetic and healthy rats

“…75 mg/kg STZ induced diabetes (27). Zhao et al determined an increase in the apoptotic cell count and a decrease in SOD, TSH and LH in the testis tissue of rats 2 months after the onset of diabetes (28). In another study, it was reported that LH and FSH decreased, and this decrease was more than 50 % in serum testosterone in 12-week diabetic rats (29).…”