Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M‐ZDF and M‐ZL) or vehicle as control groups (C‐ZDF and C‐ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C‐ZDF in comparison with C‐ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic‐induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M‐ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.
Background: The purpose of this study was to compare the biocompatibility of three bioactive materials, namely ACTIVA bioactive restorative resin composite, iRoot BP plus and Mineral Trioxide Aggregate (MTA) Angelus-HP. Methods: Seventy-five Wistar male rats were subjected to subcutaneous implantation of four polyethylene tubes; one empty tube was used as control (Group 1), and the other tubes were filled with ACTIVA (Group 2), iRoot BP (Group 3) and MTA-HP (Group 4). Then, the rats were subdivided into 3 groups according to the sacrification time into one, two and 4 weeks (n = 25 rats). Tissue specimens were submitted to histopathological and immunohistochemical analysis of α-SMA and caspase 3. Results: The one-way Anova test revealed that ACTIVA group exhibited minimal inflammation in comparison to calcium silicate cements (iRoot BP and MTA-HP groups). iRoot BP group significantly revealed a more severe degree of chronic inflammation in comparison to other groups (P < 0.05). ACTIVA group showed marked regression of inflammation and fibrosis comparable to the control, while iRoot BP group revealed remarkable fibrosis and calcification, with less degrees in MTA-HP group (P < 0.05). Immunostaining of both α-SMA and caspase 3 revealed lower indexes in ACTIVA group consistent with the control (P < 0.05). Conclusions: ACTIVA showed a higher degree of biocompatibility to subcutaneous tissues in comparison to both iRoot BP and MTA-HP cements in regard to decrease the intensity of inflammation, with subsequent fibrous connective tissue remodeling and better healing patterns. Clinical significance: Preliminary data suggests that the application of ACTIVA in retrograde fillings.
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