Effect of Titanium Dioxide and Silver Nanoparticles on Mitochondrial Dynamics in Mouse Testis Tissue.

This study was performed to investigate whether the toxicity of nanoparticles (Ag NPs or TiO2 NPs) affected mitochondrial dynamics (mitochondrial fusion and fission mechanisms) in testicular cells of mice. Animals were assigned into three groups (ten mice per group): control group (distilled water), TiO2 NP group (5 mg/kg per dose), and Ag NP group (5 mg/kg per dose). NPs were administered intravenously (via tail vein) to mice with 3-day intervals. To determine the possible toxic effect of NPs on mitochondrial dynamics, the expression levels of mitochondrial fission (Drp1)- and fusion (Mfn1, Mfn2, OPA1)-related genes were analyzed. The results showed that both Ag NPs and TiO2 NPs entered the testis via the blood-testis barier and accumulated in mouse testis tissue. Experiments showed that administration of Ag NPs neither alters testicular weight and testicular index nor causes significant toxic effect on sperm parameters. RT-PCR analysis demonstrated that Ag NP treatment did not disrupt mitochondrial dynamics in testicular cells. Conversely, administration of TiO2 NPs (anatase, < 25 nm) decreased the sperm motility and the percentages of sperms with swollen tail. Furthermore, RT-PCR and western blot analyses showed that TiO2 NPs disrupted mitochondrial dynamics by causing excess mitochondrial fission (excess expression of Drp1 gene and DRP1 protein). This is the first report on the toxicity of nanoparticles on mitochondrial dynamics (fusion and fission mechanisms) in testicular cells.

Tip60 might be a candidate for the acetylation of hepatic carbonic anhydrase I and III in mice.

BACKGROUND: Carbonic anhydrases (CAs) play a significant role in maintaining pH balance by catalyzing the conversion of carbon dioxide to bicarbonate. The regulation of pH is critical for all living organisms. Although there are many studies in the literature on the biochemical, functional, and structural features of CAs, there is not sufficient information about the epigenetic regulation of CAs. METHODS AND RESULTS: The lysine acetyltransferase TIP60 (60 kDa Tat-interactive protein) was knocked out specifically in mouse liver using the Cre/loxP system, and knockout rate was shown as 83-88% by Southern blot analysis. The impact of Tip60 on the expression of Ca1, Ca3, and Ca7 was investigated at six Zeitgeber time (ZT) points in the control and liver-specific Tip60 knockout mice (mutant) groups by real-time PCR. In the control group, while Ca1 showed the highest expression at ZT8 and ZT12, the lowest expression profile was observed at ZT0 and ZT20. Hepatic Ca1 displayed robust circadian expression. However, hepatic Ca3 exhibited almost the same level of expression at all ZT points. The highest expression of Ca7 was observed at ZT12, and the lowest expression was determined at ZT4. Furthermore, hepatic Ca7 also showed robust circadian expression. The expression of Ca1 and Ca3 significantly decreased in mutant mice at all time periods, but the expression of Ca7 used as a negative control was not affected. CONCLUSIONS: It was suggested for the first time that Tip60 might be considered a candidate protein in the regulation of the Ca1 and Ca3 genes, possibly by acetylation.

Effect of a Prolonged Dietary Iron Intake on the Gene Expression and Activity of the Testicular Antioxidant Defense System in Rats.

Despite the fact that iron represents a crucial element for the catalysis of many metabolic reactions, its accumulation in the cell leads to the production of reactive oxygen species (ROS), provoking pathological conditions such as cancer, cardiovascular diseases, diabetes, neurodegenerative diseases, and fertility. Thus, ROS are neutralized by the enzymatic antioxidant system for the purpose of protecting cells against any damage. Iron is a potential risk factor for male fertility. However, the mechanism of action of iron on the testicular antioxidant system at the gene and protein levels is not fully understood. Thus, the purpose of the current research was to ensure a better understanding of how the long-term iron treatment influences both gene expression and enzyme activities of the testicular antioxidant system in rat testis. The data of our study showed that a significant dose-dependent increase occurred in the iron level in rat testis. A reduction occurred in reduced glutathione (GSH) levels, which represent a marker of oxidative stress, along with long-term iron overload. The expression and activity of glucose 6-phosphate dehydrogenase (G6pd), glutathione reductase (Gr), glutathione peroxidase (Gpx), and glutathione S-transferases (Gst) were significantly affected by the presence of iron. The findings of the current research demonstrate that the long-term toxic dietary iron overload influences the gene expression and enzyme activity of the testicular antioxidant defense system, but the actual effect occurs at the protein level. This may modify the sperm function and dysfunction of the male reproductive system.

In vitro and in vivo effects of iron on the expression and activity of glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase in rat spleen.

Iron is an indispensable element for vital activities in almost all living organisms. It is also a cofactor for many proteins, enzymes, and other essential complex biochemical processes. Therefore, iron trafficking is firmly regulated by Hepcidin (Hamp), which is regarded as the marker for iron accumulation. The disruption of iron homeostasis leads to oxidative stress that causes various human diseases, but this mechanism is still unclear. The aim of this study is to provide a better in vivo and in vitro understanding of how long-term iron overload affects the gene expression and activities of some antioxidant enzymes, such as glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and glutathione reductase (GR) in the spleen. The findings of this study show that iron overload reduces the gene expression of G6pd, 6pgd, and Gr, but its actual effect was on the protein level.