Alejandro Apolinar-Iribe

ZnO nanoparticles (ZnONPs) have been shown to have therapeutic potential in some diseases such as diabetes and cancer. However, concentration-dependent adverse effects have also been reported. Studies which evaluate the effects of ZnONPs on the cardiovascular system are scarce. This study aimed to evaluate the cardiovascular effects of a low dose of ZnONPs administered chronically in healthy rats. Changes in dyslipidemia biomarkers, blood pressure, aortic wall structure, vascular contractility, and expression of cannabinoid receptors in the aorta wall were evaluated. Healthy rats were divided into two groups: control or treated (one, two, and three months). The treated rats received an oral dose of 10 mg/kg/day. The results showed that treatment with ZnONPs induced dyslipidemia from the first month, increasing atherosclerosis risk, which was confirmed by presence of atherosclerotic alterations revealed by aorta histological analysis. In in vitro assays, ZnONPs modified the aorta contractile activity in response to the activation of cannabinoid receptors (CB₁ and CB₂). The expression of CB₁ and CB₂ was modified as well. Moreover, ZnONPs elicited an increase in blood pressure. In conclusion, long-time oral administration of ZnONPs induce dyslipidemia and atherosclerosis eliciting alterations in aorta contractility, CB₁ and CB₂ receptors expression, and an increase in blood pressure in healthy rats.

Different studies in experimental diabetes models suggest that zinc oxide nanoparticles (ZnONPs) are useful as antidiabetic agents. However, this evidence was performed and measured in long-term treatments and with repeated doses of ZnONPs. This work aimed to evaluate the ZnONPs acute effects on glycemia during the next six h after an oral or intraperitoneal administration of the treatment in healthy and diabetic rats. In this study, the streptozotocin-nicotinamide intraperitoneal administration in male Wistar rats were used as a diabetes model. 10 mg/kg ZnONPs did not modify the baseline glucose in any group. Nevertheless, the ZnONPs short-term administration (100 mg/kg) induced a hyperglycemic response in a dose and route-dependent administration in healthy (130 ± 2 and 165 ± 10 mg/dL with oral and intraperitoneal, respectively) and diabetic rats (155 ± 2 and 240 ± 20 mg/dL with oral, and intraperitoneal, respectively). The diabetic rats were 1.5 fold more sensitive to ZnONPs effect by the intraperitoneal route. In conclusion, this study provides new information about the acute response of ZnONPs on fasting glycemia in diabetic and healthy rat models; these data are essential for possible future clinical approaches.

In the present study, we studied the effect of streptozotocin-induced Type 1 diabetes on contractile properties of soleus muscle in female and young male rats. We hypothesized that the gender affects the contractile function in diabetic rats. Thirty-two Sprague-Dawley rats, male and female, three months old were divided into four groups: Female Non-Diabetic (FND), Female Diabetic (FD), Male Non-Diabetic (MND) and Male Diabetic (MD). Diabetes was induced by a single dose of 60 mg/kg body weight of streptozotocin in citrate buffer pH 4.5 by intraperitoneal route. At 4 weeks after of the dose animals were considered to be diabetic if they had glucose levels >= 20 mmol/L. Soleus muscle mass and twitch force were higher in MND than in FND; in male rats, the diabetes decreased the muscle mass in 34% and the twitch force decayed in 33%; while in diabetic females the muscle mass and twitch force decayed 15% and 10% respectively. Our results showed that the diabetes has gender-dependent effects on the muscle mass and maximal contractile force.